I never suffocated myself so not entirely sure, but when you suffocate, it's painful, right? But of course different kind of pain than being injured or sick. What I'm wondering is, if the "painful" (or suffering) experience of suffocation involves the standard pain pathway mediated by nociceptors? Or is it some other kind of pain pathway due to a lack of oxygen? I don't mean psychological pain.
This is more of a hypothesis
I am not sure if suffocation per se would cause pain. Asphyxia, as RoryM indicated in their comments, can lead to anxiety and panic but not really pain. However, forceful breathing may lead to muscular fatigue which may result in pain. Pain induced by muscle fatigue is called myalgia. Myalgia is possibly triggered by low pH generated by lactic acid, via ASIC3 (Acid Sensing Ion Channel) receptor. Carbon dioxide has no role in this process either directly or as a synergist.
Alan R. Light, Charles J. Vierck, and Kathleen C. Light. (2010) Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes. Boca Raton, FL: CRC Press; Chapter 11 (Myalgia and Fatigue)
Being no expert on pain, I will share some thoughts on the issue.
According to the following site(http://www.helpforpain.com/arch2000dec.htm), there are two types of pain: nociceptive and neuropathic pain. Neuropathic pain involves the central and peripheral nervous system, a possibility I would discount due to no apparent link to suffocation.
Thus, it is likely that, if "traditional pain" is felt, nociceptors are involved. A possible pathway is the decrease in oxygen, possibly detected by certain nociceptors which respond to lead to pain. However, I have not suffocated either, not met anyone suffocating so this is only a possibility.
A Role for Inflammation in Chronic Pain
Recent studies indicate that inflammatory events induced by nerve injury play a central role in the pathogenesis of neuropathic pain. These involve inflammatory cells (eg, macrophages), the production of molecules that mediate inflammation (cytokines/interleukins), and the production of nerve growth factor (NGF). However, in many instances, neuropathic pain is associated with nerve inflammation, neuritis, in the absence of nerve injury. Studies on the role of cytokines in neuropathic pain have only recently begun, mostly in model systems that involve nerve injury. Little is known about the role of inflammation in neuropathic pain in the absence of nerve injury. We developed an animal model to study neuropathic pain and underlying inflammatory mechanisms in a system in which neuropathic pain is induced by nerve inflammation in the absence of injury, neuritis. Neuritis is provoked by local application of complete Freund's adjuvant (CFA) on the sciatic nerve. The following events in the course of experimental neuritis are described: 1) the time course of neuropathic pain, 2) the structural changes in axons and myelin, and 3) the spontaneous electrical activity (peripheral sensitization). It is conceivable that biochemical and physiologic changes (inflammatory mediators) that occur along the "pain pathway" (nociceptors, peripheral nerve, dorsal root ganglion ), dorsal root, neurons in the spinal cord) may sensitize one or all these sites along the pain pathway and hence lead to chronic pain).
The Myth of the Pain Receptors
This is an exciting time to be in the massage profession, with research that is shedding new light on different facets of our work. Pain is the most common reason people seek the care of a massage therapist, and the more we understand about pain, the better we can participate in a comprehensive solution to address it. A key misunderstanding with a number of treatment strategies is the role of nociceptors (which many call pain receptors).
Many of us in the healthcare professions today were taught a relatively simple, and decidedly mechanistic, physiological explanation for how pain is perceived and transmitted in the body. This model actually goes back to the time of the philosopher, Rene Descartes, in the 17 th century. Descartes’ philosophy has carried through to form the philosophical foundation of our perspective of the body. When you hear the term, “Cartesian”, in relation to mathematical or scientific ideas, that means to some extent it follows Descartes’ influence.
Our understanding of pain transmission has, of course, evolved since the time of Descartes, but there is a great deal of similarity between his original ideas and those of our recent training. Yet much of the ‘body as a machine’ philosophy – i.e. the mechanistic view of the body -continues. Descartes suggested that when there is a noxious stimulus, like getting too close to a fire, a pain stimulus traveled from the contact point along a pathway of pain fibers to the brain (Image 1). Based on this idea, the predominant methods of pain management involved trying to block pain fibers before they got to the brain. This idea has continued to influence modern pain management to a significant degree.
Image 1: The drawing from Descartes indicating pain pathways
More recent neuroscience has modified these ideas, but many are still taught that the body has pain receptors that once stimulated, send a pain signal to the brain. However, there aren’t actually ‘pain receptors’ so to speak. But, before we get into the finer details of how pain interpretation actually works, let’s explore a simple example to see why that idea doesn’t pan out.
If you were crossing the street in a quiet neighborhood with no traffic and suddenly sprained your ankle while in the middle of the road, there’s a good chance you would feel pain right away and then calmly limp to the side of the road. If, however, you were crossing a very busy street when you sprained your ankle and also noticed a large bus bearing down on you, your reaction would be quite different. Most likely you would sprint to safety on the side of the road first. Only then would you begin to feel pain in your ankle. If there were pain receptors in your ankle, they would send pain signals to the brain immediately in either instance. In the second example, the ankle pain may have kept you from focusing on the more important survival task of the moment—getting out of the way of the oncoming bus!
We now recognize that pain is far more complex than previously thought. Pain signals do involve sensory receptors connected to nerve fibers that go to the brain. The sensory receptors responsible for sending information about a noxious stimulus, like when you sprain your ankle, are called nociceptors. They are sensitive to chemical, mechanical, and thermal stimuli. But pain isn’t felt until the brain receives those signals and interprets the input as pain. This activity happens instantaneously and it isn’t under conscious control.
It is helpful to think about pain as an alarm that is generated by our body, just like the alarm system that may be protecting a home. Multiple sensors around the house are detecting motion or sound and the system is determining which ones are minor (like a leaf falling in front of the door) and which ones are important (someone breaking into the house). The alarm signal doesn’t go off with every sensor change, only with the ones that are indicative of a potential threat. Just like that alarm system for your house, the nociceptors send many signals to the brain but the alarm (pain) isn’t set off until that information is processed and it is determined that a significant threat exists.
Therefore, we now talk about pain being an output of the brain and not a ‘pain signal’ that is coming from the periphery and traveling to the brain. It is very much like the other senses we have. For our hearing, sound waves are captured by the eardrum, but it is not conceived of as a recognizable sound until the brain organizes the information received from the sensory receptors in our ear. The idea that pain is an output of the brain should not be confused with dismissive statements that are often given to patients whose pain is still a mystery to their healthcare provider. In some cases when a healthcare professional has not been able to identify a clear biological cause of pain, the patient or client may be told the pain is psychosomatic or “all in their head.” That is NOT what is being implied by stating pain is an output of the brain.
Pain can come from many factors and pain without obvious tissue damage is just as real as pain felt by the person who has an observable injury. It is common to find people who have very little or no apparent tissue damage but a great deal of pain. Conversely, it is also easy to find people who have significant tissue damage, but no pain (or pain that comes on much later than the initial tissue insult). Examples include highly competitive athletes or soldiers where individuals were severely injured but did not feel pain because there was something more important that the brain was focused on (winning the competition in the athletic example, or staying alive in the event of battlefield injury). Both of these situations produce a clinical conundrum that is hard to explain with the former Cartesian model of pain receptors sending pain signals from the periphery to the brain. So how do pain signals actually work?
To fully grasp how pain sensations are produced, it is helpful to review some basic principles of neuroanatomy. Not all massage therapists are taught these details about the nervous system in their basic training, so this is a great opportunity to polish your understanding of these concepts.
Nerve fibers are classified according to their diameter. There are 4 primary types of nerves that play a major role in our experience of pain. They are named with letters from our alphabet as well as the Greek alphabet. These four primary types of nerve fibers and their key characteristics are shown in Box 1
|Fiber Type Name||Myelinated||Primary Responsibility|
|Aα (alpha)||Yes||Proprioception: muscle spindle and golgi tendon organ|
|Aδ (delta)||Thinly myelinated||Free nerve endings & nociceptors for touch and pressure, cold receptors|
|C||Non-myelinated||Nociceptors and warmth receptors|
When a nerve fiber is myelinated, that means it is covered by a myelin sheath (Image 2). The myelin sheath helps the nerve impulse travel along the length of the nerve at a much faster rate. The rate of signal transmission plays a crucial role in pain perception and also how that sensation can be magnified or diminished.
Image 2: Myelin sheath surrounding a nerve fiber
Image courtesy of Wikipedia
Nerves that carry nociceptive signals are primarily the Aδ and C fibers, although there is some indication that nociceptive input can travel along the Aβ fibers in some cases. Often when you have an acute injury you feel a sudden sharp and strong pain first that is followed by a more persistent dull aching pain afterward. The strong and sharp pain is mostly from Aδ fiber signals which arrive at the brain before the slower, non-myelinated nociceptive signals from the C fibers. The C fibers are responsible for the latent dull aching pain that comes on after the immediate pain from an injury. There is also an indication that C fiber nociceptive signals are mainly responsible for many of the chronic pain complaints that persist for long periods of time. 1
In 1965 two researchers, Ronald Melzack and Patrick Wall, published a paper outlining a new theory of pain modulation that emphasized an expanded role for the central nervous system and de-emphasized the notion of pain receptors in the periphery and the idea they were sending ‘pain signals’ to the brain. This theory has come to be known as the Gate Theory of pain. While it has been modified from its original presentation, there is still strong evidence to support the idea that signal transmission and the experience of pain can be modified the way they originally described it. Let’s take a look at how that works.
Nociceptive signals are sent from specialized sensory receptors in the periphery of the body. Once those sensory receptors are activated they send a message primarily along the Aδ and C fibers. But the body is also getting sensory information from other receptors simultaneously. Proprioceptive signals about the body’s position in space and signals about joint position from mechanoreceptors are traveling on the much faster Aα and Aβ nerve fibers. They get to ‘processing stations’ in the spinal cord and central nervous system faster than the nociceptive signals traveling on the Aδ and C fibers (Image 3).
Image 3: Schematic representation of the Gate Theory
Mediclip image copyright (1998) Williams & Wilkins. All Rights Reserved.
The gate theory suggests that there is a neurological ‘gate’ (not truly a mechanical gate, but a metaphorical one) in the spinal cord that closes down to limit the amount of information being sent to the brain for processing. When the proprioceptive signals arrive at the gate first, the gate shuts down to the slower-traveling nociceptive signals. With fewer nociceptive signals getting through, there is decreased pain sensation. The benefit of mechanoreceptors and proprioceptors outpacing the nociceptive signals means that the most important stimuli is perceived by the brain first, as in the example of the person with the sprained ankle sprinting to the sidewalk to avoid a bus. This mechanism also explains why rubbing a painful body area reduces the pain experienced in that moment.
Massage therapists should take note that some of the positive effects of massage related to pain management may very well be attributed to mechanisms described by the gate theory. We have yet to research this fully, but certain techniques like active engagement methods where there is simultaneous massage along with concentric or eccentric muscle engagement may be capitalizing on the pain gating process. It is likely that proprioceptive information coming from the massage technique along with the joint movement and muscle contraction closes the gate on nociceptive signals and thereby decreases pain.
Our current understanding of pain signal transmission also sheds some interesting light on pain experiences our clients present to us. When nociceptive signals reach the central nervous system they travel through the spinal cord and then ascend through the lower, mid, and upper portions of the brain until they are fully processed. As they travel through these different sections, the intensity of the signals can be altered. Various factors can cause pain signals to be amplified this is called ascending facilitation. Think of it as ‘turning up the volume’ on the nociceptive signals that are arriving. Ascending facilitation can create two characteristic clinical experiences hyperalgesia and allodynia. Hyperalgesia is when something is much more painful than it ordinarily should be. Allodynia is when something is painful that shouldn’t be (like when a client reports that gently stroking the skin is painful). Obviously our goals of pain treatment are to decrease any ascending facilitation that may be occurring.
There is a corresponding process that ‘turns down the volume’ on nociceptive signals and is very helpful for decreasing the client’s pain experience. When various pleasurable sensations (like massage) are experienced, the upper portions of the brain can send signals to the lower sections and block a certain amount of nociceptive input, decreasing the person’s sensations of pain. This process is called descending inhibition (or descending modulation). There is some research that now suggests this may be one of the most important benefits of massage when it comes to pain management. 2
There are fascinating new developments in our understanding of how pain is experienced and the various strategies we can use to help manage our client’s pain. The more we understand about the pain process, the better we will be at adapting our massage treatment to take the best advantage of how pain transmission occurs in the body. In upcoming installments we will further explore some of these important concepts about how to use this new research to best help our clients.
Merskey, H. & Bogduk, N. Classification of Chronic Pain (IASP, Seattle, 1994).
Staud, R., Nagel, S. & Robinson, M.E. Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: A randomized, double-blind, placebo-controlled study. Pain 145, 96–104 (2009).
Price, D.D. et al. Widespread hyperalgesia in irritable bowel syndrome is dynamically maintained by tonic visceral impulse input and placebo/nocebo factors: evidence from human physchophysics, animal models, and neuroimaging. Neuroimage 47, 995–1001 (2009).
Price, D.D., Zhou, O., Moshiree, B., Robinson, M.E. & Verne, G.N. Peripheral and central contributions to hyperalgesia in irritable bowel syndrome. J. Pain 7, 529–535 (2006).
Verne, G.N., Robinson, M.E., Vase, L. & Price, D.D. Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients. Pain 105, 223–230 (2003).
Gracely, R.H., Lynch, S.A. & Bennett, G.J. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 51, 175–194 (1992).
Murdaca, G., Colombo, B.M. & Puppo, F. Anti–TNF-α inhibitors: a new therapeutic approach for inflammatory immune-mediated diseases: an update upon efficacy and adverse events. Int. J. Immunopathol. Pharmacol. 22, 557–565 (2009).
Bharucha, A.E. & Linden, D.R. Linaclotide—a secretagogue and antihyperalgesic agent—what next? Neurogastroenterol. Motil. 22, 227–231 (2010).
Edvinsson, L. & Ho, T.W. CGRP receptor antagonism and migraine. Neurotherapeutics 7, 164–175 (2010).
Bessou, P. & Perl, E.R. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J. Neurophysiol. 32, 1025–1043 (1969).
Kuner, R. Central mechanisms of pathological pain. Nat. Med. advance online publication doi:10.1038/nm.2231 (14 October 2010).
Caterina, M.J., Gold, M.S. & Meyer, R.A. Molecular biology of nociceptors. in The Neurobiology of Pain (eds. Hunt, S. & Koltzenburg, M.) 1–33 (Oxford Univ. Press, Oxford, 2005).
Riera, C.E., Vogel, H., Simon, S.A. & le Coutre, J. Artificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R626–R634 (2007).
Robinson, D.R. & Gebhart, G.F. Inside information—the unique features of visceral sensation. Mol. Interv. 8, 242–253 (2008).
Snider, W.D. & McMahon, S.B. Tackling pain at the source: New ideas about nociceptors. Neuron 20, 629–632 (1998).
Hökfelt, T. et al. Phenotype regulation in dorsal root ganglion neurons after nerve injury: focus on peptides and their receptors. in Molecular Neurobiology of Pain: Progress in Pain Research and Management Vol. 9 (ed. Borsook, D.) 115–143 (IASP, Seattle, 1997).
Elitt, C.M. et al. Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold. J. Neurosci. 26, 8578–8587 (2006).
Kruger, L. Morphological features of thin sensory afferent fibers: a new interpretation of 'nociceptor' function. Prog. Brain Res. 74, 253–257 (1988).
Richardson, J.D. & Vasko, M.R. Cellular mechanisms of neurogenic inflammation. J. Pharmacol. Exp. Ther. 302, 839–845 (2002).
Willis, W.D. Jr . Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp. Brain Res. 124, 395–421 (1999).
Lewis, T. Experiments relating to cutaneous hyperalgesia and its spread through somatic fibers. Clin. Sci. 2, 373–423 (1935).
Shakhanbeh, J. & Lynn, B. Morphine inhibits antidromic vasodilatation without affecting the excitability of C-polymodal nociceptors in the skin of the rat. Brain Res. 607, 314–318 (1993).
Lynn, B. & Carpenter, S.E. Primary afferent units from the hairy skin of the rat hind limb. Brain Res. 238, 29–43 (1982).
Gebhart, G.F. & Bielefeldt, K. Visceral pain. in The Senses: A Comprehensive Reference (eds. Bushnell, M.C. & Basbaum, A.I.) 543–570 (Academic, San Diego, 2008).
Schaible, H.G. & Schmidt, R.F. Responses of fine medial articular nerve afferents to passive movements of knee joints. J. Neurophysiol. 49, 1118–1126 (1983).
Meyer, R.A., Davis, K.D., Cohen, R.H., Treede, R.D. & Campbell, J.N. Mechanically insensitive afferents (MIAs) in cutaneous nerves of monkey. Brain Res. 561, 252–261 (1991).
Braz, J.M., Nassar, M.A., Wood, J.N. & Basbaum, A.I. Parallel “pain” pathways arise from subpopulations of primary afferent nociceptor. Neuron 47, 787–793 (2005).
Patel, L. & Lindley, C. Aprepitant—a novel NK1-receptor antagonist. Expert Opin. Pharmacother. 4, 2279–2296 (2003).
Ritter, A.M. & Mendell, L.M. Somal membrane properties of physiologically identified sensory neurons in the rat: effects of nerve growth factor. J. Neurophysiol. 68, 2033–2041 (1992).
Kirchhoff, C., Leah, J.D., Jung, S. & Reeh, P.W. Excitation of cutaneous senory nerve endings in the rat by 4-aminopyridine and tetraethylammonium. J. Neurophysiol. 67, 125–131 (1992).
Baumann, T.K., Chaudhary, P. & Martenson, M.E. Background potassium channel block and TRPV1 activation contribute to proton depolarization of sensory neurons from humans with neuropathic pain. Eur. J. Neurosci. 19, 1343–1351 (2004).
Harriott, A.M. & Gold, M.S. Contribution of primary afferent channels to neuropathic pain. Curr. Pain Headache Rep. 13, 197–207 (2009).
Viana, F., de la Pena, E. & Belmonte, C. Specificity of cold thermotransduction is determined by differential ionic channel expression. Nat. Neurosci. 5, 254–260 (2002).
Zimmermann, K. et al. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures. Nature 447, 855–858 (2007).
Zhao, J. et al. Small RNAs control sodium channel expression, nociceptor excitability and pain thresholds. J. Neurosci. 30, 10860–10871 (2010).
Del Camino, D. et al. TRPA1 contributes to cold hypersensitivity. J. Neurosci. (in the press).
Kremeyer, B. et al. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66, 671–680 (2010).
Woodbury, C.J. et al. Nociceptors lacking TRPV1 and TRPV2 have normal heat responses. J. Neurosci. 24, 6410–6415 (2004).
Tsunozaki, M. & Bautista, D.M. Mammalian somatosensory mechanotransduction. Curr. Opin. Neurobiol. 19, 362–369 (2009).
Kwan, K.Y., Glazer, J.M., Corey, D.P., Rice, F.L. & Stucky, C.L. TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J. Neurosci. 29, 4808–4819 (2009).
Price, M.P. et al. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron 32, 1071–1083 (2001).
Patel, A.J. & Honore, E. Properties and modulation of mammalian 2P domain K + channels. Trends Neurosci. 24, 339–346 (2001).
Maingret, F., Fosset, M., Lesage, F., Lazdunski, M. & Honore, E. TRAAK is a mammalian neuronal mechano-gated K + channel. J. Biol. Chem. 274, 1381–1387 (1999).
Cummins, T.R. et al. A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons. J. Neurosci. 19, RC43 (1999).
Gold, M.S. & Caterina, M.J. Molecular biology of nociceptor transduction. in The Senses: A Comprehensive Reference Vol. 5 (eds. Basbaum, A.I. & Bushnell, M.C.) 43–74 (Academic, San Diego, 2008).
Waxman, S.G. Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nat. Neurosci. 10, 405–409 (2007).
Reimann, F. et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc. Natl. Acad. Sci. USA 107, 5148–5153 (2010).
Liu, B. et al. The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K + channels and activation of Ca 2+ -activated Cl − channels. J. Clin. Invest. 120, 1240–1252 (2010).
Alves, D.P. et al. Additive antinociceptive effect of the combination of diazoxide, an activator of ATP-sensitive K + channels, and sodium nitroprusside and dibutyryl-cGMP. Eur. J. Pharmacol. 489, 59–65 (2004).
Steranka, L.R., Burch, R.M., Vavrek, R.J., Stewart, J.M. & Enna, S.J. Multiple bradykinin receptors: results of studies using a novel class of receptor antagonists. Adv. Exp. Med. Biol. 236, 111–127 (1988).
Russell, F.A., Veldhoen, V.E., Tchitchkan, D. & McDougall, J.J. Proteinase-activated receptor-4 (PAR4) activation leads to sensitization of rat joint primary afferents via a bradykinin B2 receptor–dependent mechanism. J. Neurophysiol. 103, 155–163 (2010).
Schaible, H.G., Ebersberger, A. & Von Banchet, G.S. Mechanisms of pain in arthritis. Ann. NY Acad. Sci. 966, 343–354 (2002).
Mousa, S.A. Morphological correlates of immune-mediated peripheral opioid analgesia. Adv. Exp. Med. Biol. 521, 77–87 (2003).
Tfelt-Hansen, P., De Vries, P. & Saxena, P.R. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs 60, 1259–1287 (2000).
Potrebic, S., Ahn, A.H., Skinner, K., Fields, H.L. & Basbaum, A.I. Peptidergic nociceptors of both trigeminal and dorsal root ganglia express serotonin 1D receptors: implications for the selective antimigraine action of triptans. J. Neurosci. 23, 10988–10997 (2003).
Dao, T.T., Lund, J.P., Remillard, G. & Lavigne, G.J. Is myofascial pain of the temporal muscles relieved by oral sumatriptan? A cross-over pilot study. Pain 62, 241–244 (1995).
Harriott, A.M. & Gold, M.S. Serotonin type 1D receptors (5HTR) are differentially distributed in nerve fibres innervating craniofacial tissues. Cephalalgia 28, 933–944 (2008).
Carlton, S.M. & Hargett, G.L. Colocalization of metabotropic glutamate receptors in rat dorsal root ganglion cells. J. Comp. Neurol. 501, 780–789 (2007).
Hucho, T.B., Dina, O.A. & Levine, J.D. Epac mediates a cAMP-to-PKC signaling in inflammatory pain: an isolectin B4 + neuron-specific mechanism. J. Neurosci. 25, 6119–6126 (2005).
Lewin, G.R. & Mendell, L.M. Nerve growth factor and nociception. Trends Neurosci. 16, 353–359 (1993).
Amir, R. et al. The role of sodium channels in chronic inflammatory and neuropathic pain. J. Pain 7, S1–S29 (2006).
Rukwied, R. et al. NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin. Pain 148, 407–413 (2010).
Hefti, F.F. et al. Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol. Sci. 27, 85–91 (2006).
Schaible, H.G. et al. The role of proinflammatory cytokines in the generation and maintenance of joint pain. Ann. NY Acad. Sci. 1193, 60–69 (2010).
Abbadie, C. et al. Chemokines and pain mechanisms. Brain Res. Brain Res. Rev. 60, 125–134 (2009).
Ren, K. & Dubner, R. Interactions between the immune and nervous systems in pain. Nat. Med. advance online publication doi:10.1038/nm.2234 (14 October 2010).
Fehrenbacher, J.C. et al. Rapid pain modulation with nuclear receptor ligands. Brain Res. Brain Res. Rev. 60, 114–124 (2009).
Walder, R.Y. et al. ASIC1 and ASIC3 play different roles in the development of hyperalgesia after inflammatory muscle injury. J. Pain 11, 210–218 (2010).
Shinoda, M., Feng, B. & Gebhart, G.F. Peripheral and central P2X receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse. Gastroenterology 137, 2096–2104 (2009).
Vaughn, A.H. & Gold, M.S. Ionic mechanisms underlying inflammatory mediator–induced sensitization of dural afferents. J. Neurosci. 30, 7878–7888 (2010).
Backonja, M.M. & Stacey, B. Neuropathic pain symptoms relative to overall pain rating. J. Pain 5, 491–497 (2004).
Janig, W., Grossmann, L. & Gorodetskaya, N. Mechano- and thermosensitivity of regenerating cutaneous afferent nerve fibers. Exp. Brain Res. 196, 101–114 (2009).
McLachlan, E.M., Janig, W., Devor, M. & Michaelis, M. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature 363, 543–546 (1993).
Rush, A.M. et al. A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc. Natl. Acad. Sci. USA 103, 8245–8250 (2006).
Sengupta, J.N. & Gebhart, G.F. Mechanosensitive afferent fibers in the gastrointestinal and lower urinary tracts. in Visceral Pain, Progress in Pain Research and Management Vol. 5 (ed. Gebhart, G.F.) 75–98 (IASP, Seattle, 1995).
Page, A.J. et al. Different contributions of ASIC channels 1a, 2 and 3 in gastrointestinal mechanosensory function. Gut 54, 1408–1415 (2005).
Dubreuil, A.S. et al. Role of T-type calcium current in identified D-hair mechanoreceptor neurons studied in vitro. J. Neurosci. 24, 8480–8484 (2004).
Honore, P. et al. A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel transient receptor potential type V1 receptor antagonist, relieves pathophysiological pain associated with inflammation and tissue injury in rats. J. Pharmacol. Exp. Ther. 314, 410–421 (2005).
Alessandri-Haber, N., Dina, O.A., Chen, X. & Levine, J.D. TRPC1 and TRPC6 channels cooperate with TRPV4 to mediate mechanical hyperalgesia and nociceptor sensitization. J. Neurosci. 29, 6217–6228 (2009).
Brierley, S.M. et al. The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli. Gastroenterology 137, 2084–2095 (2009).
Maingret, F., Patel, A.J., Lesage, F., Lazdunski, M. & Honore, E. Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J. Biol. Chem. 274, 26691–26696 (1999).
Alloui, A. et al. TREK-1, a K + channel involved in polymodal pain perception. EMBO J. 25, 2368–2376 (2006).
Burnstock, G. Purinergic mechanosensory transduction and visceral pain. Mol. Pain 5, 69 (2009).
Noël, J. et al. The mechano-activated K + channels TRAAK and TREK-1 control both warm and cold perception. EMBO J. 28, 1308–1318 (2009).
Bautista, D.M. et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124, 1269–1282 (2006).
Karashima, Y. et al. TRPA1 acts as a cold sensor in vitro and in vivo. Proc. Natl. Acad. Sci. USA 106, 1273–1278 (2009).
Kwan, K.Y. et al. TRPA1 contributes to cold, mechanical and chemical nociception but is not essential for hair-cell transduction. Neuron 50, 277–289 (2006).
Bautista, D.M. et al. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448, 204–208 (2007).
McKemy, D.D., Neuhausser, W.M. & Julius, D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416, 52–58 (2002).
Peier, A.M. et al. A heat-sensitive TRP channel expressed in keratinocytes. Science 296, 2046–2049 (2002).
Güler, A.D. et al. Heat-evoked activation of the ion channel, TRPV4. J. Neurosci. 22, 6408–6414 (2002).
Burnstock, G. Purinergic receptors and pain. Curr. Pharm. Des. 15, 1717–1735 (2009).
Camilleri, M. Review article: new receptor targets for medical therapy in irritable bowel syndrome. Aliment. Pharmacol. Ther. 31, 35–46 (2010).
Rau, K.K., Johnson, R.D. & Cooper, B.Y. Nicotinic AChR in subclassified capsaicin-sensitive and -insensitive nociceptors of the rat DRG. J. Neurophysiol. 93, 1358–1371 (2005).
Carlton, S.M. & Coggeshall, R.E. Inflammation-induced changes in peripheral glutamate receptor populations. Brain Res. 820, 63–70 (1999).
Price, T.J., Cervero, F., Gold, M.S., Hammond, D.L. & Prescott, S.A. Chloride regulation in the pain pathway. Brain Res. Brain Res. Rev. 60, 149–170 (2009).
Michaelis, M., Blenk, K.H., Vogel, C. & Janig, W. Distribution of sensory properties among axotomized cutaneous C-fibres in adult rats. Neuroscience 94, 7–10 (1999).
Howe, J.F., Loeser, J.D. & Calvin, W.H. Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression. Pain 3, 25–41 (1977).
Kohno, T. et al. Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord. Pain 117, 77–87 (2005).
Tsuzuki, K. et al. Differential regulation of P2X3 mRNA expression by peripheral nerve injury in intact and injured neurons in the rat sensory ganglia. Pain 91, 351–360 (2001).
Birder, L.A. & Perl, E.R. Expression of α2-adrenergic receptors in rat primary afferent neurones after peripheral nerve injury or inflammation. J. Physiol. (Lond.) 515, 533–542 (1999).
Immediate Responses to Noxious Stimulation in Gastropod Molluscs
To protect their soft bodies, most molluscs produce a hard shell, but many lack a shell or enough of a shell for adequate protection and must rely on other defenses. Among the seven extant taxonomic classes of molluscs, only two have been studied extensively by behavioral scientists and neurobiologists: Gastropoda and Cephalopoda, both of which include many species possessing little or no shell. The gastropods represent 80% of molluscan species and occupy an enormous range of marine, freshwater, and terrestrial habitats. Within Mollusca, only the coleoid cephalopods (octopus, cuttlefish, and squid) have more complex nervous systems and behaviors. Selected cephalopods and gastropods first attracted the attention of neuroscientists because their giant axons and neuronal somata permitted cellular studies that, until a few decades ago, were impossible in mammals. From the 1960s through the 1990s numerous laboratories exploited the experimental advantages of uniquely identifiable neurons in central neural circuits of gastropods to directly relate cellular and synaptic properties to the organization and mediation of defensive, feeding, and reproductive behaviors (Kandel, 1979 Chase, 2002). Unusual advantages include large neuronal somata (cell bodies) that (1) exhibit overshooting action potentials, (2) allow high-fidelity somal monitoring of synaptic potentials, and (3) display exceptional tolerance for prolonged or repeated impalement by micropipettes.
Behavioral Responses to Noxious Stimulation in Gastropod Molluscs
Many mechanistic studies have focused on synaptic alterations underlying aversive learning and memory in the large marine snail, Aplysia californica (Kandel, 2001), which possesses only a rudimentary, internal shell that provides little or no protection. Associated behavioral studies of learning in Aplysia utilized electric shock to the soft body surface to modify behavior. Such shock was considered aversive because it evoked the same immediate defensive responses as produced either by strong mechanical pinch delivered to the body by an experimenter (which produced signs of tissue injury), by bites during staged attacks from a predatory gastropod, Pleurobranchaea californica, or by application of a chemical stimulus, NaCl crystals, to the skin (Walters and Erickson, 1986 Walters, 1994 Gasull et al., 2005). Noxious stimuli produced local withdrawal, directed release of ink and other defensive secretions, and escape locomotion directed away from the point of 𠇊ttack” (Walters and Erickson, 1986). These responses are examples of active defenses that are common throughout the animal kingdom (Edmunds, 1974 Kavaliers, 1988 Walters, 1994): most notably, withdrawal, retaliation (in this case by directed ejection of offending chemicals) (Kicklighter et al., 2005 Love-Chezem et al., 2013), and flight. Production of defensive responses in Aplysia is accompanied by inhibition of competing behavioral responses (Walters et al., 1981 Illich et al., 1994 Acheampong et al., 2012).
Nociceptors That Detect Noxious Stimulation in Gastropod Molluscs
Although electric shock is an artificial stimulus, shock delivered to the body surface of Aplysia evokes strong defensive responses indistinguishable from those activated by natural stimuli because the shock activates peripheral axons of the same primary nociceptors that are activated by noxious mechanical pressures (Walters et al., 1983a Illich and Walters, 1997). Important functional properties of identified nociceptors in Aplysia (Walters et al., 1983a, 2004 Frost et al., 1997 Illich and Walters, 1997) – especially a relatively high threshold for activation by mechanical stimuli, and silence in the absence of noxious stimulation – are typical of mechano-nociceptors described in diverse animals, including leech (Nicholls and Baylor, 1968), lamprey (Martin and Wickelgren, 1971), teleost fish (Ashley et al., 2007) frog (Hamamoto and Simone, 2003), snake (Liang and Terashima, 1993), chicken (Koltzenburg and Lewin, 1997), mouse (Koltzenburg et al., 1997), rat (Handwerker et al., 1987), cat (Burgess and Perl, 1967), and monkey (Perl, 1968).
The nociceptors identified in Aplysia have coiled peripheral terminals embedded in the muscle layer rather than the skin (Steffensen and Morris, 1996), which can explain why sharp poking or pinching stimuli produce optimal activation, and light, brushing stimuli are ineffective. Unlike the nociceptors in insects discussed below, these neurons have somata located within central ganglia, far from their more vulnerable peripheral terminals. These nociceptors show functional properties (Walters et al., 1983a, 2004 Illich and Walters, 1997) more similar to mechanosensitive nociceptors in mammals that are myelinated, rapidly conducting, and rapidly adapting (Aδ- and Aβ-nociceptors) than to unmyelinated, slowly conducting and slowly adapting, often polymodal (chemosensitive) C-nociceptors (Light et al., 1992 Djouhri and Lawson, 2004). Myelin does not occur in molluscs (Roots, 2008), so increased conduction velocity depends upon increased axonal diameter. Aplysia nociceptors have central cell bodies and axonal diameters that, while not large compared to axons of truly giant neurons in Aplysia (Rayport et al., 1983 Steffensen et al., 1995), are much larger than the small axons coming from the far more numerous afferent neurons of unknown function that possess peripheral cell bodies (Xin et al., 1995). Relatively rapid conduction in Aplysia nociceptors and rapid adaptation are functionally consistent with rapid detection of the onset of threatening peripheral stimulation rather than provision of continuing information to the CNS about ongoing (e.g., inflammatory) noxious states, which in mammals is primarily provided by C-nociceptors (Odem et al., 2018). It is not known whether any of the small-diameter afferents or other sensory neurons in Aplysia have functions equivalent to those of mammalian C-fiber nociceptors – especially, the non-accommodating activity continuously induced by persistent states of injury and/or inflammation. Among all invertebrates, the leech N lateral neurons are the only nociceptors shown to have non-accommodating, polymodal properties (as well as weak capsaicin sensitivity) resembling the properties of mammalian C-fiber nociceptors (Pastor et al., 1996).
Transduction of noxious cold
Identifying the mechanisms used by nociceptors to transduce noxious cold has lagged behind progress in understanding heat transduction mechanisms (65). The intensity of cold pain in humans increases linearly with stimulus intensity between about 20ଌ and 0ଌ. The threshold for pain perception to cold is much less precise than that for heat, but is about 15ଌ (66). There is tremendous variability in threshold for cutaneous cold-evoked fiber activity observed in mammals in part due to the rate of cooling (approximately +30ଌ to ଌ refs. 27, 66). Homeostatic processes engaged during in vivo studies (e.g., vasculature changes) and potential tissue damage occurring at subfreezing temperatures are likely to indirectly influence nociceptor responsiveness. Furthermore, measuring cold nocifensive behavior in animals has proven to be challenging, perhaps due to the prolonged exposure time in most assays (68).
Cooling the skin to 4ଌ activates A- and C-fibers sensitive to innocuous cooling and cold-sensitive nociceptors (27, 67, 69), consistent with the presence of two populations of cold-sensitive neurons observed in culture (70). Cool-sensitive nonnociceptive afferents are spontaneously active at normal skin temperature and their excitability increases with decreasing temperature (53, 67). The menthol-activated NSC channel TRPM8 (10) is responsible for the detection of innocuous cooling (69, 73, 74) and contributes to spontaneous firing (69) in mice. The effective range for TRPM8-mediated cold coding extends from just below skin temperature into the noxious range (10ଌଌ and below ref. 10). Although mouse studies have yielded conflicting results regarding the requirement of TRPM8 in behavioral responses to noxious stimuli, more recent work using a novel cold-plate assay convincingly demonstrates a role for mouse TRPM8 in sensing noxious cold (75). Furthermore, the analgesic effects of cold temperature (17ଌ) were lost in mice lacking TRPM8 in the context of formalin-induced inflammation (74). Whether TRPM8-mediated analgesia is dependent on peripheral and/or central sites of action is unknown but may be addressed now that TRPM8-expressing neurons and their peripheral and central fibers can be visualized by GFP expression driven by the TRPM8 promoter (76, 77). Importantly, studies in humans and mice reveal species differences in pathways sensing innocuous cold: A-fiber block completely suppresses the cold response in humans (78), yet the majority of TRPM8-expressing fibers responsible for innocuous cold transduction in mice have small diameters (76, 77)
Noxious cold stimuli activate NSC currents and calcium influx (10, 79) and decrease K + channel activity (80) and Na + /K + -ATPase function (65) (Table (Table3). 3 ). The temporal dissociation of the qualities of pain/ache vs. prickle/heat to noxious cold (3ଌ) suggest underlying differences in transduction mechanisms or information processing (66). The cation channel TRPA1 (10) has been proposed to play a role in this process because it has a threshold near 17ଌ, is expressed in nociceptors together with TRPV1 (10), and is required for cold sensation in mice (81, 82). Human genetic studies have suggested TRPA1 contributes to variation in cold-pain sensitivity (5). Although TRPA1 may respond to cold indirectly through cold-induced intracellular calcium release (10), slow temperature ramps can activate TRPA1 in excised patches in the absence of calcium (82, 83). However, the contribution of TRPA1 to cold sensation is debated since TRPA1 activation was not observed in a heterologous expression system or cultured TG neurons to which relatively short cold stimuli to 5ଌ were applied (84), and not all mouse lines constitutively lacking TRPA1 reveal a cold phenotype in behavioral and neural assays (85). However, two independent studies recently demonstrated a role of TRPA1 in noxious cold sensitivity (75, 82). TRPA1 is established as a general sensor for noxious irritating electrophilic compounds (including allyl isothiocyanate [mustard oil] [AITC] and cinnamaldehyde, the active pungent ingredients in hot mustard and cinnamon, respectively refs. 84 and 86) and is sensitized by inflammatory mediators (87). These electrophilic agonists open an integral channel pore by covalent binding to the intracellular N terminus of the channel protein (88, 89). Importantly, endogenous reactive chemicals are also effective agonists of TRPA1 (90). How TRPA1-expressing neurons might mediate the burning sensation of hot mustard (AITC) may be explained by anatomical and psychophysical results: AITC is a strong chemical activator of a subset of TRPV1-expressing neurons, and activity in peripheral fibers transmitting information about cold stimuli in the presence of an A-fiber block (presumably C-fibers) evoke burning, aching, and pricking qualities (67). Interestingly, the activation of some cold fibers by noxious heat may be the basis for the paradoxical cold sensation felt by stimulating cold spots with noxious heat stimuli (67).
First attested in English in 1297, the word peyn comes from the Old French peine, in turn from Latin poena meaning "punishment, penalty"  (in L.L. also meaning "torment, hardship, suffering") and that from Greek ποινή (poine), generally meaning "price paid, penalty, punishment".  
The International Association for the Study of Pain recommends using specific features to describe a patient's pain:
- region of the body involved (e.g. abdomen, lower limbs),
- system whose dysfunction may be causing the pain (e.g., nervous, gastrointestinal),
- duration and pattern of occurrence,
- intensity, and
- cause 
Chronic vs acute Edit
Pain is usually transitory, lasting only until the noxious stimulus is removed or the underlying damage or pathology has healed, but some painful conditions, such as rheumatoid arthritis, peripheral neuropathy, cancer and idiopathic pain, may persist for years. Pain that lasts a long time is called "chronic" or "persistent", and pain that resolves quickly is called "acute". Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time between onset and resolution the two most commonly used markers being 3 months and 6 months since the onset of pain,  though some theorists and researchers have placed the transition from acute to chronic pain at 12 months.  : 93 Others apply "acute" to pain that lasts less than 30 days, "chronic" to pain of more than six months' duration, and "subacute" to pain that lasts from one to six months.  A popular alternative definition of "chronic pain", involving no arbitrarily fixed duration, is "pain that extends beyond the expected period of healing".  Chronic pain may be classified as "cancer-related" or "benign." 
Allodynia is pain experienced in response to a normally painless stimulus.  It has no biological function and is classified by stimuli into dynamic mechanical, punctate and static.  
Phantom pain is pain felt in a part of the body that has been amputated, or from which the brain no longer receives signals. It is a type of neuropathic pain. 
The prevalence of phantom pain in upper limb amputees is nearly 82%, and in lower limb amputees is 54%.  One study found that eight days after amputation, 72% of patients had phantom limb pain, and six months later, 67% reported it.   Some amputees experience continuous pain that varies in intensity or quality others experience several bouts of pain per day, or it may reoccur less often. It is often described as shooting, crushing, burning or cramping. If the pain is continuous for a long period, parts of the intact body may become sensitized, so that touching them evokes pain in the phantom limb. Phantom limb pain may accompany urination or defecation.  : 61–9
Local anesthetic injections into the nerves or sensitive areas of the stump may relieve pain for days, weeks, or sometimes permanently, despite the drug wearing off in a matter of hours and small injections of hypertonic saline into the soft tissue between vertebrae produces local pain that radiates into the phantom limb for ten minutes or so and may be followed by hours, weeks or even longer of partial or total relief from phantom pain. Vigorous vibration or electrical stimulation of the stump, or current from electrodes surgically implanted onto the spinal cord, all produce relief in some patients.  : 61–9
Mirror box therapy produces the illusion of movement and touch in a phantom limb which in turn may cause a reduction in pain. 
Paraplegia, the loss of sensation and voluntary motor control after serious spinal cord damage, may be accompanied by girdle pain at the level of the spinal cord damage, visceral pain evoked by a filling bladder or bowel, or, in five to ten per cent of paraplegics, phantom body pain in areas of complete sensory loss. This phantom body pain is initially described as burning or tingling but may evolve into severe crushing or pinching pain, or the sensation of fire running down the legs or of a knife twisting in the flesh. Onset may be immediate or may not occur until years after the disabling injury. Surgical treatment rarely provides lasting relief.  : 61–9
Breakthrough pain is transitory pain that comes on suddenly and is not alleviated by the patient's regular pain management. It is common in cancer patients who often have background pain that is generally well-controlled by medications, but who also sometimes experience bouts of severe pain that from time to time "breaks through" the medication. The characteristics of breakthrough cancer pain vary from person to person and according to the cause. Management of breakthrough pain can entail intensive use of opioids, including fentanyl.  
Asymbolia and insensitivity Edit
The ability to experience pain is essential for protection from injury, and recognition of the presence of injury. Episodic analgesia may occur under special circumstances, such as in the excitement of sport or war: a soldier on the battlefield may feel no pain for many hours from a traumatic amputation or other severe injury. 
Although unpleasantness is an essential part of the IASP definition of pain,  it is possible to induce a state described as intense pain devoid of unpleasantness in some patients, with morphine injection or psychosurgery.  Such patients report that they have pain but are not bothered by it they recognize the sensation of pain but suffer little, or not at all.  Indifference to pain can also rarely be present from birth these people have normal nerves on medical investigations, and find pain unpleasant, but do not avoid repetition of the pain stimulus. 
Insensitivity to pain may also result from abnormalities in the nervous system. This is usually the result of acquired damage to the nerves, such as spinal cord injury, diabetes mellitus (diabetic neuropathy), or leprosy in countries where that disease is prevalent.  These individuals are at risk of tissue damage and infection due to undiscovered injuries. People with diabetes-related nerve damage, for instance, sustain poorly-healing foot ulcers as a result of decreased sensation. 
A much smaller number of people are insensitive to pain due to an inborn abnormality of the nervous system, known as "congenital insensitivity to pain".  Children with this condition incur carelessly-repeated damage to their tongues, eyes, joints, skin, and muscles. Some die before adulthood, and others have a reduced life expectancy. [ citation needed ] Most people with congenital insensitivity to pain have one of five hereditary sensory and autonomic neuropathies (which includes familial dysautonomia and congenital insensitivity to pain with anhidrosis).  These conditions feature decreased sensitivity to pain together with other neurological abnormalities, particularly of the autonomic nervous system.   A very rare syndrome with isolated congenital insensitivity to pain has been linked with mutations in the SCN9A gene, which codes for a sodium channel (Nav1.7) necessary in conducting pain nerve stimuli. 
Experimental subjects challenged by acute pain and patients in chronic pain experience impairments in attention control, working memory, mental flexibility, problem solving, and information processing speed.  Acute and chronic pain are also associated with increased depression, anxiety, fear, and anger. 
If I have matters right, the consequences of pain will include direct physical distress, unemployment, financial difficulties, marital disharmony, and difficulties in concentration and attention…
On subsequent negative emotion Edit
Although pain is considered to be aversive and unpleasant and is therefore usually avoided, a meta-analysis which summarized and evaluated numerous studies from various psychological disciplines, found a reduction in negative affect. Across studies, participants that were subjected to acute physical pain in the laboratory subsequently reported feeling better than those in non-painful control conditions, a finding which was also reflected in physiological parameters.  A potential mechanism to explain this effect is provided by the opponent-process theory.
Before the relatively recent discovery of neurons and their role in pain, various different body functions were proposed to account for pain. There were several competing early theories of pain among the ancient Greeks: Hippocrates believed that it was due to an imbalance in vital fluids.  In the 11th century, Avicenna theorized that there were a number of feeling senses including touch, pain and titillation. 
In 1644, René Descartes theorized that pain was a disturbance that passed down along nerve fibers until the disturbance reached the brain.   Descartes's work, along with Avicenna's, prefigured the 19th-century development of specificity theory. Specificity theory saw pain as "a specific sensation, with its own sensory apparatus independent of touch and other senses".  Another theory that came to prominence in the 18th and 19th centuries was intensive theory, which conceived of pain not as a unique sensory modality, but an emotional state produced by stronger than normal stimuli such as intense light, pressure or temperature.  By the mid-1890s, specificity was backed mostly by physiologists and physicians, and the intensive theory was mostly backed by psychologists. However, after a series of clinical observations by Henry Head and experiments by Max von Frey, the psychologists migrated to specificity almost en masse, and by century's end, most textbooks on physiology and psychology were presenting pain specificity as fact.  
Some sensory fibers do not differentiate between noxious and non-noxious stimuli, while others, nociceptors, respond only to noxious, high intensity stimuli. At the peripheral end of the nociceptor, noxious stimuli generate currents that, above a given threshold, send signals along the nerve fiber to the spinal cord. The "specificity" (whether it responds to thermal, chemical or mechanical features of its environment) of a nociceptor is determined by which ion channels it expresses at its peripheral end. Dozens of different types of nociceptor ion channels have so far been identified, and their exact functions are still being determined. 
The pain signal travels from the periphery to the spinal cord along an A-delta or C fiber. Because the A-delta fiber is thicker than the C fiber, and is thinly sheathed in an electrically insulating material (myelin), it carries its signal faster (5–30 m/s) than the unmyelinated C fiber (0.5–2 m/s).  Pain evoked by the A-delta fibers is described as sharp and is felt first. This is followed by a duller pain, often described as burning, carried by the C fibers.  These A-delta and C fibers enter the spinal cord via Lissauer's tract and connect with spinal cord nerve fibers in the central gelatinous substance of the spinal cord. These spinal cord fibers then cross the cord via the anterior white commissure and ascend in the spinothalamic tract. Before reaching the brain, the spinothalamic tract splits into the lateral, neospinothalamic tract and the medial, paleospinothalamic tract. The neospinothalamic tract carries the fast, sharp A-delta signal to the ventral posterolateral nucleus of the thalamus. The paleospinothalamic tract carries the slow, dull, C-fiber pain signal. Some of these fibers peel off in the brain stem, connecting with the reticular formation or midbrain periaqueductal gray, and the remainder terminate in the intralaminar nuclei of the thalamus. 
Pain-related activity in the thalamus spreads to the insular cortex (thought to embody, among other things, the feeling that distinguishes pain from other homeostatic emotions such as itch and nausea) and anterior cingulate cortex (thought to embody, among other things, the affective/motivational element, the unpleasantness of pain),  and pain that is distinctly located also activates primary and secondary somatosensory cortex. 
Spinal cord fibers dedicated to carrying A-delta fiber pain signals, and others that carry both A-delta and C fiber pain signals to the thalamus have been identified. Other spinal cord fibers, known as wide dynamic range neurons, respond to A-delta and C fibers, but also to the large A-beta fibers that carry touch, pressure and vibration signals.  In 1955, DC Sinclair and G Weddell developed peripheral pattern theory, based on a 1934 suggestion by John Paul Nafe. They proposed that all skin fiber endings (with the exception of those innervating hair cells) are identical, and that pain is produced by intense stimulation of these fibers.  Another 20th-century theory was gate control theory, introduced by Ronald Melzack and Patrick Wall in the 1965 Science article "Pain Mechanisms: A New Theory".  The authors proposed that both thin (pain) and large diameter (touch, pressure, vibration) nerve fibers carry information from the site of injury to two destinations in the dorsal horn of the spinal cord, and that the more large fiber activity relative to thin fiber activity at the inhibitory cell, the less pain is felt. 
Three dimensions of pain Edit
In 1968 Ronald Melzack and Kenneth Casey described chronic pain in terms of its three dimensions:
- "sensory-discriminative" (sense of the intensity, location, quality and duration of the pain),
- "affective-motivational" (unpleasantness and urge to escape the unpleasantness), and
- "cognitive-evaluative" (cognitions such as appraisal, cultural values, distraction and hypnotic suggestion).
They theorized that pain intensity (the sensory discriminative dimension) and unpleasantness (the affective-motivational dimension) are not simply determined by the magnitude of the painful stimulus, but "higher" cognitive activities can influence perceived intensity and unpleasantness. Cognitive activities may affect both sensory and affective experience or they may modify primarily the affective-motivational dimension. Thus, excitement in games or war appears to block both the sensory-discriminative and affective-motivational dimensions of pain, while suggestion and placebos may modulate only the affective-motivational dimension and leave the sensory-discriminative dimension relatively undisturbed. (p. 432) The paper ends with a call to action: "Pain can be treated not only by trying to cut down the sensory input by anesthetic block, surgical intervention and the like, but also by influencing the motivational-affective and cognitive factors as well." (p. 435)
Pain is part of the body's defense system, producing a reflexive retraction from the painful stimulus, and tendencies to protect the affected body part while it heals, and avoid that harmful situation in the future.   It is an important part of animal life, vital to healthy survival. People with congenital insensitivity to pain have reduced life expectancy. 
In The Greatest Show on Earth: The Evidence for Evolution, biologist Richard Dawkins addresses the question of why pain should have the quality of being painful. He describes the alternative as a mental raising of a "red flag". To argue why that red flag might be insufficient, Dawkins argues that drives must compete with one other within living beings. The most "fit" creature would be the one whose pains are well balanced. Those pains which mean certain death when ignored will become the most powerfully felt. The relative intensities of pain, then, may resemble the relative importance of that risk to our ancestors. [a] This resemblance will not be perfect, however, because natural selection can be a poor designer. This may have maladaptive results such as supernormal stimuli. 
Pain, however, does not only wave a "red flag" within living beings but may also act as a warning sign and a call for help to other living beings. Especially in humans who readily helped each other in case of sickness or injury throughout their evolutionary history, pain might be shaped by natural selection to be a credible and convincing signal of need for relief, help, and care. 
Idiopathic pain (pain that persists after the trauma or pathology has healed, or that arises without any apparent cause) may be an exception to the idea that pain is helpful to survival, although some psychodynamic psychologists argue that such pain is psychogenic, enlisted as a protective distraction to keep dangerous emotions unconscious. 
In pain science, thresholds are measured by gradually increasing the intensity of a stimulus in a procedure called quantitative sensory testing which involves such stimuli as electric current, thermal (heat or cold), mechanical (pressure, touch, vibration), ischemic, or chemical stimuli applied to the subject to evoke a response.  The "pain perception threshold" is the point at which the subject begins to feel pain, and the "pain threshold intensity" is the stimulus intensity at which the stimulus begins to hurt. The "pain tolerance threshold" is reached when the subject acts to stop the pain. 
A person's self-report is the most reliable measure of pain.    Some health care professionals may underestimate pain severity.  A definition of pain widely employed in nursing, emphasizing its subjective nature and the importance of believing patient reports, was introduced by Margo McCaffery in 1968: "Pain is whatever the experiencing person says it is, existing whenever he says it does".  To assess intensity, the patient may be asked to locate their pain on a scale of 0 to 10, with 0 being no pain at all, and 10 the worst pain they have ever felt. Quality can be established by having the patient complete the McGill Pain Questionnaire indicating which words best describe their pain. 
Visual analogue scale Edit
The visual analogue scale is a common, reproducible tool in the assessment of pain and pain relief.  The scale is a continuous line anchored by verbal descriptors, one for each extreme of pain where a higher score indicates greater pain intensity. It is usually 10 cm in length with no intermediate descriptors as to avoid marking of scores around a preferred numeric value. When applied as a pain descriptor, these anchors are often 'no pain' and 'worst imaginable pain". Cut-offs for pain classification have been recommended as no pain (0-4mm), mild pain (5-44mm), moderate pain (45-74mm) and severe pain (75-100mm).  [ check quotation syntax ]
Multidimensional pain inventory Edit
The Multidimensional Pain Inventory (MPI) is a questionnaire designed to assess the psychosocial state of a person with chronic pain. Combining the MPI characterization of the person with their IASP five-category pain profile is recommended for deriving the most useful case description. 
Assessment in non-verbal people Edit
Non-verbal people cannot use words to tell others that they are experiencing pain. However, they may be able to communicate through other means, such as blinking, pointing, or nodding. 
With a non-communicative person, observation becomes critical, and specific behaviors can be monitored as pain indicators. Behaviors such as facial grimacing and guarding (trying to protect part of the body from being bumped or touched) indicate pain, as well as an increase or decrease in vocalizations, changes in routine behavior patterns and mental status changes. Patients experiencing pain may exhibit withdrawn social behavior and possibly experience a decreased appetite and decreased nutritional intake. A change in condition that deviates from baseline, such as moaning with movement or when manipulating a body part, and limited range of motion are also potential pain indicators. In patients who possess language but are incapable of expressing themselves effectively, such as those with dementia, an increase in confusion or display of aggressive behaviors or agitation may signal that discomfort exists, and further assessment is necessary. Changes in behavior may be noticed by caregivers who are familiar with the person's normal behavior. 
Infants do feel pain, but lack the language needed to report it, and so communicate distress by crying. A non-verbal pain assessment should be conducted involving the parents, who will notice changes in the infant which may not be obvious to the health care provider. Pre-term babies are more sensitive to painful stimuli than those carried to full term. 
Another approach, when pain is suspected, is to give the person treatment for pain, and then watch to see whether the suspected indicators of pain subside. 
Other reporting barriers Edit
The way in which one experiences and responds to pain is related to sociocultural characteristics, such as gender, ethnicity, and age.   An aging adult may not respond to pain in the same way that a younger person might. Their ability to recognize pain may be blunted by illness or the use of medication. Depression may also keep older adult from reporting they are in pain. Decline in self-care may also indicate the older adult is experiencing pain. They may be reluctant to report pain because they do not want to be perceived as weak, or may feel it is impolite or shameful to complain, or they may feel the pain is a form of deserved punishment.  
Cultural barriers may also affect the likelihood of reporting pain. Sufferers may feel that certain treatments go against their religious beliefs. They may not report pain because they feel it is a sign that death is near. Many people fear the stigma of addiction, and avoid pain treatment so as not to be prescribed potentially addicting drugs. Many Asians do not want to lose respect in society by admitting they are in pain and need help, believing the pain should be borne in silence, while other cultures feel they should report pain immediately to receive immediate relief. 
Gender can also be a perceived factor in reporting pain. Gender differences can be the result of social and cultural expectations, with women expected to be more emotional and show pain, and men more stoic.  As a result, female pain is often stigmatized, leading to less urgent treatment of women based on social expectations of their ability to accurately report it.  This leads to extended emergency room wait times for women and frequent dismissal of their ability to accurately report pain.  
Diagnostic aid Edit
Pain is a symptom of many medical conditions. Knowing the time of onset, location, intensity, pattern of occurrence (continuous, intermittent, etc.), exacerbating and relieving factors, and quality (burning, sharp, etc.) of the pain will help the examining physician to accurately diagnose the problem. For example, chest pain described as extreme heaviness may indicate myocardial infarction, while chest pain described as tearing may indicate aortic dissection.  
Physiological measurement Edit
Functional magnetic resonance imaging brain scanning has been used to measure pain, and correlates well with self-reported pain.   
Nociceptive pain is caused by stimulation of sensory nerve fibers that respond to stimuli approaching or exceeding harmful intensity (nociceptors), and may be classified according to the mode of noxious stimulation. The most common categories are "thermal" (e.g. heat or cold), "mechanical" (e.g. crushing, tearing, shearing, etc.) and "chemical" (e.g. iodine in a cut or chemicals released during inflammation). Some nociceptors respond to more than one of these modalities and are consequently designated polymodal.
Nociceptive pain may also be classed according to the site of origin and divided into "visceral", "deep somatic" and "superficial somatic" pain. Visceral structures (e.g., the heart, liver and intestines) are highly sensitive to stretch, ischemia and inflammation, but relatively insensitive to other stimuli that normally evoke pain in other structures, such as burning and cutting. Visceral pain is diffuse, difficult to locate and often referred to a distant, usually superficial, structure. It may be accompanied by nausea and vomiting and may be described as sickening, deep, squeezing, and dull.  Deep somatic pain is initiated by stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fasciae and muscles, and is dull, aching, poorly-localized pain. Examples include sprains and broken bones. Superficial somatic pain is initiated by activation of nociceptors in the skin or other superficial tissue, and is sharp, well-defined and clearly located. Examples of injuries that produce superficial somatic pain include minor wounds and minor (first degree) burns. 
Neuropathic pain is caused by damage or disease affecting any part of the nervous system involved in bodily feelings (the somatosensory system).  Neuropathic pain may be divided into peripheral, central, or mixed (peripheral and central) neuropathic pain. Peripheral neuropathic pain is often described as "burning", "tingling", "electrical", "stabbing", or "pins and needles".  Bumping the "funny bone" elicits acute peripheral neuropathic pain.
Nociplastic pain is pain characterized by a changed nociception (but without evidence of real or threatened tissue damage, or without disease or damage in the somatosensory system). 
This applies, for example, to fibromyalgia patients.
Psychogenic pain, also called psychalgia or somatoform pain, is pain caused, increased or prolonged by mental, emotional or behavioral factors.  Headache, back pain and stomach pain are sometimes diagnosed as psychogenic.  Sufferers are often stigmatized, because both medical professionals and the general public tend to think that pain from a psychological source is not "real". However, specialists consider that it is no less actual or hurtful than pain from any other source. 
People with long-term pain frequently display psychological disturbance, with elevated scores on the Minnesota Multiphasic Personality Inventory scales of hysteria, depression and hypochondriasis (the "neurotic triad"). Some investigators have argued that it is this neuroticism that causes acute pain to turn chronic, but clinical evidence points the other direction, to chronic pain causing neuroticism. When long-term pain is relieved by therapeutic intervention, scores on the neurotic triad and anxiety fall, often to normal levels. Self-esteem, often low in chronic pain patients, also shows improvement once pain has resolved.  : 31–2
Pain can be treated through a variety of methods. The most appropriate method depends upon the situation. Management of chronic pain can be difficult and may require the coordinated efforts of a pain management team, which typically includes medical practitioners, clinical pharmacists, clinical psychologists, physiotherapists, occupational therapists, physician assistants, and nurse practitioners. 
Inadequate treatment of pain is widespread throughout surgical wards, intensive care units, and accident and emergency departments, in general practice, in the management of all forms of chronic pain including cancer pain, and in end of life care.        This neglect extends to all ages, from newborns to medically frail elderly.   In the US, African and Hispanic Americans are more likely than others to suffer unnecessarily while in the care of a physician   and women's pain is more likely to be undertreated than men's. 
The International Association for the Study of Pain advocates that the relief of pain should be recognized as a human right, that chronic pain should be considered a disease in its own right, and that pain medicine should have the full status of a medical specialty.  It is a specialty only in China and Australia at this time.  Elsewhere, pain medicine is a subspecialty under disciplines such as anesthesiology, physiatry, neurology, palliative medicine and psychiatry.  In 2011, Human Rights Watch alerted that tens of millions of people worldwide are still denied access to inexpensive medications for severe pain. 
Acute pain is usually managed with medications such as analgesics and anesthetics.  Caffeine when added to pain medications such as ibuprofen, may provide some additional benefit.   Ketamine can be used instead of opioids for short-term pain.  Pain medications can cause paradoxical side effects, such as opioid-induced hyperalgesia (severe pain caused by long-term opioid use).  
Sugar (sucrose) when taken by mouth reduces pain in newborn babies undergoing some medical procedures (a lancing of the heel, venipuncture, and intramuscular injections). Sugar does not remove pain from circumcision, and it is unknown if sugar reduces pain for other procedures.  Sugar did not affect pain-related electrical activity in the brains of newborns one second after the heel lance procedure.  Sweet liquid by mouth moderately reduces the rate and duration of crying caused by immunization injection in children between one and twelve months of age. 
Individuals with more social support experience less cancer pain, take less pain medication, report less labor pain and are less likely to use epidural anesthesia during childbirth, or suffer from chest pain after coronary artery bypass surgery. 
Suggestion can significantly affect pain intensity. About 35% of people report marked relief after receiving a saline injection they believed to be morphine. This placebo effect is more pronounced in people who are prone to anxiety, and so anxiety reduction may account for some of the effect, but it does not account for all of it. Placebos are more effective for intense pain than mild pain and they produce progressively weaker effects with repeated administration.  : 26–8 It is possible for many with chronic pain to become so absorbed in an activity or entertainment that the pain is no longer felt, or is greatly diminished.  : 22–3
Cognitive behavioral therapy (CBT) has been shown effective for improving quality of life in those with chronic pain but the reduction in suffering is modest, and the CBT method employed was not shown to have any effect on outcome.  Acceptance and commitment therapy (ACT) may be effective in the treatment of chronic pain,  as may mindfulness-based pain management (MBPM).   
A number of meta-analyses have found clinical hypnosis to be effective in controlling pain associated with diagnostic and surgical procedures in both adults and children, as well as pain associated with cancer and childbirth.  A 2007 review of 13 studies found evidence for the efficacy of hypnosis in the reduction of chronic pain under some conditions, though the number of patients enrolled in the studies was low, raising issues related to the statistical power to detect group differences, and most lacked credible controls for placebo or expectation. The authors concluded that "although the findings provide support for the general applicability of hypnosis in the treatment of chronic pain, considerably more research will be needed to fully determine the effects of hypnosis for different chronic-pain conditions." 
Alternative medicine Edit
An analysis of the 13 highest quality studies of pain treatment with acupuncture, published in January 2009, concluded there was little difference in the effect of real, faked and no acupuncture.  However, more recent reviews have found some benefit.    Additionally, there is tentative evidence for a few herbal medicines.  There has been some interest in the relationship between vitamin D and pain, but the evidence so far from controlled trials for such a relationship, other than in osteomalacia, is inconclusive. 
For chronic (long-term) lower back pain, spinal manipulation produces tiny, clinically insignificant, short-term improvements in pain and function, compared with sham therapy and other interventions.  Spinal manipulation produces the same outcome as other treatments, such as general practitioner care, pain-relief drugs, physical therapy, and exercise, for acute (short-term) lower back pain. 
Pain is the main reason for visiting an emergency department in more than 50% of cases,  and is present in 30% of family practice visits.  Several epidemiological studies have reported widely varying prevalence rates for chronic pain, ranging from 12 to 80% of the population.  It becomes more common as people approach death. A study of 4,703 patients found that 26% had pain in the last two years of life, increasing to 46% in the last month. 
A survey of 6,636 children (0–18 years of age) found that, of the 5,424 respondents, 54% had experienced pain in the preceding three months. A quarter reported having experienced recurrent or continuous pain for three months or more, and a third of these reported frequent and intense pain. The intensity of chronic pain was higher for girls, and girls' reports of chronic pain increased markedly between ages 12 and 14. 
The nature or meaning of physical pain has been diversely understood by religious or secular traditions from antiquity to modern times.  
Physical pain is an important political topic in relation to various issues, including pain management policy, drug control, animal rights or animal welfare, torture, and pain compliance. In various contexts, the deliberate infliction of pain in the form of corporal punishment is used as retribution for an offence, or for the purpose of disciplining or reforming a wrongdoer, or to deter attitudes or behaviour deemed unacceptable. The slow slicing, or death by a thousand cuts, was a form of execution in China reserved for crimes viewed as especially severe, such as high treason or patricide. In some cultures, extreme practices such as mortification of the flesh or painful rites of passage are highly regarded. For example, the Sateré-Mawé people of Brazil use intentional bullet ant stings as part of their initiation rites to become warriors. 
The most reliable method for assessing pain in most humans is by asking a question: a person may report pain that cannot be detected by any known physiological measure. However, like infants, animals cannot answer questions about whether they feel pain thus the defining criterion for pain in humans cannot be applied to them. Philosophers and scientists have responded to this difficulty in a variety of ways. René Descartes for example argued that animals lack consciousness and therefore do not experience pain and suffering in the way that humans do.  Bernard Rollin of Colorado State University, the principal author of two U.S. federal laws regulating pain relief for animals, [b] writes that researchers remained unsure into the 1980s as to whether animals experience pain, and that veterinarians trained in the U.S. before 1989 were simply taught to ignore animal pain.  In his interactions with scientists and other veterinarians, he was regularly asked to "prove" that animals are conscious, and to provide "scientifically acceptable" grounds for claiming that they feel pain.  Carbone writes that the view that animals feel pain differently is now a minority view. [ citation needed ] Academic reviews of the topic are more equivocal, noting that although the argument that animals have at least simple conscious thoughts and feelings has strong support,  some critics continue to question how reliably animal mental states can be determined.   The ability of invertebrate species of animals, such as insects, to feel pain and suffering is also unclear.   
The presence of pain in an animal cannot be known for certain, but it can be inferred through physical and behavioral reactions.  Specialists currently believe that all vertebrates can feel pain, and that certain invertebrates, like the octopus, may also.    As for other animals, plants, or other entities, their ability to feel physical pain is at present a question beyond scientific reach, since no mechanism is known by which they could have such a feeling. In particular, there are no known nociceptors in groups such as plants, fungi, and most insects,  except for instance in fruit flies. 
In vertebrates, endogenous opioids are neuromodulators that moderate pain by interacting with opioid receptors.  Opioids and opioid receptors occur naturally in crustaceans and, although at present no certain conclusion can be drawn,  their presence indicates that lobsters may be able to experience pain.   Opioids may mediate their pain in the same way as in vertebrates.  Veterinary medicine uses, for actual or potential animal pain, the same analgesics and anesthetics as used in humans. 
SA in Nociceptor Somata is Correlated with and may Help Drive Pain-Related Behavior after SCI
The incidence of somal SA after SCI was significantly correlated with behavioral hypersensitivity tested 1 and 3𠄵 months after injury the animals showing the greatest sensitivity to mechanical and thermal test stimuli applied to all four paws also had the highest incidence of nociceptor SA recorded in vitro (Bedi et al., 2010). Significant correlations between mechanical or thermal hypersensitivity and incidence of nociceptor SA were found for hindlimb responses, which were correlated with SA in neurons from L4/L5 DRG. Furthermore, forelimb responses were correlated with SA in the above-level neurons sampled from T8, T9, C6, and C7 DRG. Particularly interesting effects of SCI were found on vocalization elicited by mechanical stimuli delivered to an array of test sites on the back. SCI dramatically reduced the incidence of vocalization evoked by below-level test stimuli, suggesting substantial interruption of spinal pathways traversing the injury site. Conversely, SCI increased the incidence of vocalization to above-level stimuli, and the above-level vocalization was correlated with SA in neurons sampled from at- and above-level DRG. Surprisingly, relatively little chronic SA was observed in somata of neurons from C6/C7 DRG influences of nociceptor SA on supraspinal responses and forelimb responsiveness may come from wide-ranging effects of active nociceptors in above-level DRG closer to the injury site, or from nociceptor SA generated in the periphery (Carlton et al., 2009).
SA generated within somata and peripheral branches of nociceptors is likely to drive central sensitization (Carlton et al., 2009 Bedi et al., 2010). If this SA also drives pain-related behavioral alterations, then manipulations that selectively block the SA should reduce the behavior. The nociceptor-specific Na + channel, Nav1.8 is important for the expression of nociceptor SA and other sensitizing effects in other pain models (Lai et al., 2002 Roza et al., 2003 Jarvis et al., 2007 Abrahamsen et al., 2008). Importantly, knocking down the expression of Nav1.8 largely eliminates SCI-induced nociceptor SA in vitro and greatly reduces behavioral hypersensitivity to mechanical and thermal test stimulation applied in vivo (Yang et al., 2012). This finding indicates that SA and hyperexcitability in primary nociceptors plays a major part in driving chronic hypersensitivity and possibly pain after SCI.
Chapter 23 - Pain
This chapter provides an overview of the current understanding of pain processing mechanisms with emphasis on the contributions made by the mouse. The application of molecular genetics to pain research has provided great insights into mechanisms underlying the complex sensory experience called “pain.” In broad terms, pain research using mice can be divided into three areas: work on naïve or normal animals aimed at increasing the understanding of pain processing mechanisms work using mouse models of experimentally-induced pain where the goal is to uncover mechanisms that drive or amplify pain responses and work where genetically modified mice are used to explore the role of various proteins or neuron types in pain processing mechanisms and circuits. Knockout and transgenic mice have been used to firmly establish the identity and understand the role of key proteins involved in transmitting information about noxious stimuli from the periphery into the spinal cord, and via the ascending pain pathway to the cerebral cortex. In the periphery, studies have identified a variety of sensors involved in detecting specific types of noxious stimuli, the second messenger pathways involved in sensitizing nociceptors in certain inflammatory and neuropathic pain models, and the identity and role of certain sodium channels that are largely confined to the transmission of information about tissue damage. In the CNS, particularly the dorsal horn of the spinal cord, genetically modified mice have allowed the study of specific genetically tagged neuron types, and helped in building better models of spinal cord pain circuits.
- Abbott, J. (2014). Self‐medication in insects: current evidence and future perspectives. Ecological Entomology, 39(3), 273-280.
- Barron, A. B., & Klein, C. (2016). What insects can tell us about the origins of consciousness. Proceedings of the National Academy of Sciences, 113(18), 4900-4908.
- Bentley, A. J., Newton, S., & Zio, C. D. (2003). Sensitivity of sleep stages to painful thermal stimuli. Journal of sleep research, 12(2), 143-147.
- Diegelmann, S., Zars, M., & Zars, T. (2006). Genetic dissociation of acquisition and memory strength in the heat-box spatial learning paradigm in Drosophila. Learning & Memory, 13(1), 72-83.
- Gerber, B., Yarali, A., Diegelmann, S., Wotjak, C. T., Pauli, P., & Fendt, M. (2014). Pain-relief learning in flies, rats, and man: basic research and applied perspectives. Learning & Memory, 21(4), 232-252.
- Gherardi, F., Aquiloni, L., & Tricarico, E. (2012). Revisiting social recognition systems in invertebrates. Animal cognition, 15(5), 745-762.
- Kim, H. G., Margolies, D., & Park, Y. (2015). The roles of thermal transient receptor potential channels in thermotactic behavior and in thermal acclimation in the red flour beetle, Tribolium castaneum. Journal of insect physiology, 76, 47-55.
13 Responses to Do insects feel pain?
THE ONES I HAD IN MY 55 YEAR OLD MATTRESS IF INJURED 1 IT WOULD CHARGE ME.I THINK THAT ANSWERS YOUR QUESTION. ALL I HAD TO DO WAS ROLL OVER IN BED AND GET A STING. THEY WERE CAMOUFLAGED LIGHT GREY WITH SPARKLING BUNCHES OF LEGS ON EITHER SIDE .THEY ALSO HAD 2 BLACK SPOT EYES AND 2 WINGS ON EACH SIDE WITH A LOBSTER SHAPED TAIL. SOME WERE 1&1/2 INCHES LONG. IF THESE WERE WERE FOUND OUT BY HOLLYWOOD THEY WOULD MAKE A GREAT MONSTER WITH ALL THE LEGS ON THE SIDES AT THE FRONT AND IF ANGERED WOULD KILL SMALL INSECTS AND IF HUMAN SIZE –I DO NOT EVEN WANT TO THINK ABOUT THOSE UGLY NASTY THINGS BEING ANY BIGGER.
MY QUESTION IS ARE THEY RELATED TO SCORPION FLIES? A BOOK I HAVE FOR A LONG TIME READ THERE ARE OVER 1,000 VARIETIES OF THOSE FLIES.
THEY SEEMED TO HAVE A WHOLE ENTOURAGE OF FLIES AND LITTLE HARD SHELLED INSECTS WHERE EVER THEY ARE. IT IS REALLY STRANGE THE ADULT ONES ARE MUCH SMALLER AND HAVE FEWER STINGING LEGS. I BROKE A FLY SWATTER ON THEM NIGHT AFTER NIGHT SEALING THEM IN UNTIL BLEACH KILLED THEM. ANT AND ROACH KILLER DID NOTHING. THE BIGGER ONES WOULD COME OUT AND IMMEDIATELY FIND A DEAD 1 AND BEGIN TO EAT IT.
These studies appear to be done on larvae and adults. Do pupae feel pain?
Why are you shouting? Those insects sound interesting. I might draw them.
Just out of curiosity, I caught a fly, and broke a leg off. Not trying to hurt it, just an experiment. The fly didn’t appear to have any pain, the next day, I broke another leg off. Still not appearing to be in any pain. It was still flying. Then I put it in the freezer, after it froze, I took it out of the freezer, it thawed out and flew away. My conclusion was that flies do not experience pain. Not sure about other insects, but with the small size of their brains, I do not believe they have the capability of of experiencing pain.
It should be considered that nociception as a withdrawal or escape behavior motivator is quite obvious in brainless creatures. But sweeten up the spot and it will keep coming no matter how many times you zap it (eg, bait a window glass with a bit of sugar and see how a fly keeps coming back for the sweetness. It’s not dumb it just feels the sugar more than suffering noxious stimuli. Given the escape but not avoid reaction does not mean that the fly doesn’t feel pain, causing it to fly away, but that it doesn’t suffer so it keeps coming back for the sweet. Spiders and all other fly-catchers count on that so they wait for the inevitable return. Had the fly suffered, return would not have come so quickly so not suffering but arousal of defense circuits is what pain does. Indeed, many insect species while being eaten from the back keep eating after escape proves futile. But we recognize pain by the attempted escape reaction, though only suffering leads to long term defense and avoidance. Yet we can be like flies too. In fact we know that with certain lesions in the CNS people do not feel pain, nor will they engage in withdrawal movements. Indeed, some feel pleasure where you feel suffering pain. Other lesions cause all the defense and escape behaviors but not avoidance. While with other lesions victims will withdraw but not know why. To suffer, animals must have a certain number of neuronal circuits We now have robots that upon signal of damage become hyperactive as programmed to rapidly engage in repair programs. On the other hand, we see seizure like activity in flies (intense seemingly purposeless movements) which like post-ichtal behavior are exhausting but do not seem to alter behavior patterns. Injury seems to cause a lot of motility, but does not seem to produce learned avoidance. Therefore, no lingering evasion lessons seem to have been learned as the attractive power of a nociceptive experience does not seem to provoke avoidance. For example, spray a fly with Lysol (ammonia) spray, a costly experiment, and it will constantly return to a sugar coated spot. But a bee, ah that’s a real genius!
Lastly, endogenous endorphins do cause some to tolerate amazing pain. Some people have no pain too but they die young due to an amazing degree of self injury. However,hen you see the suffering of people with terminal cancers, for example, you realize that nature doesn’t give a damn. Suffering went way beyond pain for one reason: why not? The genetics of evolution is heartless to its errors as DNA changes randomly.