{"id":218293,"date":"2016-05-27T14:52:28","date_gmt":"2016-05-27T17:52:28","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/en\/?p=218293"},"modified":"2016-05-27T14:52:28","modified_gmt":"2016-05-27T17:52:28","slug":"adjusting-the-theory-of-pain","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/adjusting-the-theory-of-pain\/","title":{"rendered":"Adjusting the theory of pain"},"content":{"rendered":"

\"052-053_Dor_239\"<\/a>The pain that is felt in a phantom limb\u2014in a part of the body that no longer exists, for instance\u2014is no fantasy brought about by the loss of an arm or a leg.\u00a0 The pain might be indeed real.\u00a0 One of the hypotheses that have been raised to explain this phenomenon suggests that the regrowth of nerve fibers around the absent body part produces involuntary stimuli that the brain interprets as pain.\u00a0 Another hypothesis, introduced recently, suggests that when nerve fibers transmitting stimuli to the medulla are ruptured, medullar\u00a0\u00a0 neurons can become hypersensitive and carry pain signals to the brain, even when stimuli that normally elicit sensations of pain are absent.<\/p>\n

Basing his view on a proposal for readjusting the classic, 50-year-old theory of pain physiology, Francisco Javier Ropero Pel\u00e1ez, a professor at the Federal University of the ABC in Santo Andr\u00e9, thinks more along the lines of this second hypothesis.\u00a0 Pal\u00e1ez\u2019s approach also offers new insights into dysesthesia, a neurological disturbance that can cause a mere touch to be interpreted as a stimulus capable of triggering intense pain (such as fibromyalgia, accompanied by chronic, generalized muscle pain).<\/p>\n

In a 1965 article in Science<\/em>, psychologist Ronald Melzak of McGill University and MIT neuroscientist Patrick Wall introduced their \u201cgate control\u201d theory of pain, building on existing approaches and careful analysis of Ren\u00e9 Descartes\u2019s 1664 treatise on the subject.\u00a0 Often mentioned in the neurological literature, the Melzak\/Wall approach describes how neurons interpret different stimuli that the brain might or might not perceive as pain.\u00a0 According to their theory, there are two kinds of stimuli: the first travels from nociceptive cells, in the form of thin nerve fibers, innervating skin, muscles, bones, and internal organs, triggering aversive signals such as those of intense heat (fire) or a deep cut, as from a knife (see Pesquisa <\/em>FAPESP Issue n\u00ba 155<\/a>); and the second stimulus, originating from the endings of large nerve fibers, is triggered mechanically through touch, pressure, or vibration.<\/p>\n

The two types of fibers conduct signals to two types of medullar neurons that act as gateways for pain transmission, either blocking or releasing stimuli.\u00a0 When receiving stimuli from both types of fibers, the first neuron (interneuron) transmits the signal to the second neuron only if the stimulus originates from the nociceptive fiber.\u00a0 This theory explains how people are able to use electric hair-removal devices, which work by massaging the skin, relieving the sensation of pain even as the follicles are being pulled out.<\/p>\n

Hypotheses<\/strong>
\nIn 2014, Lorne Mendell of the University of New York at Stoney Brook remarked that the model that Melzak\/Wall presented in their Science <\/em>article \u201cis incorrect in every detail.\u201d\u00a0 One year earlier, two Canadian researchers pointed out an excessive number oversimplifications and errors in the Melzak\/Wall theory\u2019s presentation of both the neural architecture of the spinal cord and the location and interaction of nerve fibers.\u00a0 Pel\u00e1ez was particularly unsettled by the claim that the nociceptive fiber can at once inhibit one neuron and stimulate another.\u00a0 In his view, inhibition cannot occur because the substances responsible for transmitting or blocking stimuli (identified sometime after the publication of the 1965 Science <\/em>article) cannot trigger contrary responses from the endings of a single neuron.<\/p>\n

The discovery of this likely error, along with evidence pointing to the adaptability of neurons, encouraged Pel\u00e1ez and Professor Shirley Taniguchi, a pharmacologist at the Albert Einstein College of Health Sciences, to create a neuro-computational model (described in the journal Neural Plasticity<\/em>, November, 2015) that allows for variations in neural sensitivity and interconnectedness in the face of stimuli.\u00a0 In 1996, researchers at the University of Bath in the UK, having devised a mathematical model to explain certain phenomena in connection with pain, had already observed variations in the sensitivity of neurons responding disproportionately to changes in the intensity of stimuli.<\/p>\n

According to Pel\u00e1ez, pain triggered by tactile stimuli\u2014such as that found in certain varieties of dysesthesia\u2014can occur when nerve fibers transmitting mechanical stimuli lose a layer of their lining and, consequently, interpret signals more slowly (similar to aversive-stimuli fibers), thereby confusing the medullary neurons as to the signal\u2019s origin.\u00a0 \u201cThere are several other hypotheses for explaining hypersensitivity to pain,\u201d says Thiago Cunha, a professor and pharmacologist at the Ribeir\u00e3o Preto School of Medicine (FMRP-USP).\u00a0 According to Cunha, there is evidence suggesting that interneurons can lose their capacity for target selectivity\u2014or even die\u2014allowing signals to travel more easily through pathways to the brain.\u00a0 Another hypothesis raises the possibility of a reduction in the function or levels of the GABA neurotransmitter (which inhibits nerve stimuli), or that GABA-receptors malfunction and stimulate the neurons that they would normally inhibit.<\/p>\n

After developing and publishing his own pain gate theories, Pel\u00e1ez went on to discuss his approach with biomedical researchers, respond to the bewilderment that arose over his mathematical interpretation of biological phenomena, and, finally, demonstrate how his work could be useful.\u00a0 According to Taniguchi, with whom he co-wrote his Neural Plasticity <\/em>article, Pel\u00e1ez\u2019s new approach explains how drugs like gabapentin (which inhibits neural sensation) work. \u00a0According to their theory, Taniguchi and Pel\u00e1ez suggest that phantom pain can be controlled by administering gabapentin immediately following amputation and before medullar neurons become hypersensitive and release pain signals despite the absence of actual stimuli.<\/p>\n

Scientific articles<\/em>
\nMELZACK, R. and WALL, P. D. Pain mechanisms: a new theory<\/a>.\u00a0 Science<\/strong>.\u00a0 V. 150, no. 3699.\u00a0 1965.
\nMOAYEDI, M. and DAVIS, K. D. Theories of pain: from specificity to gate control<\/a>.\u00a0 Journal of Neurophysiology<\/strong>.\u00a0 V. 109, no.\u00a0 2013.
\nPEL\u00c1EZ, F.\u00a0 J. R.\u00a0and TANIGUCHI, S.\u00a0 The Gate Theory of pain revisited: Modeling different pain conditions with a parsimonious neurocomputational model<\/a>.\u00a0 Neural Plasticity<\/strong>.\u00a0 V. 752807.\u00a0 2015.
\nMENDELL, L. M. Constructing and deconstructing the gate theory of pain<\/a>.\u00a0 Pain<\/strong>.\u00a0 V. 155, no. 2.\u00a0 2014.<\/p>\n","protected":false},"excerpt":{"rendered":"Adaptations lead to new insights into phantom pain","protected":false},"author":17,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[159],"tags":[247,250],"coauthors":[5968],"class_list":["post-218293","post","type-post","status-publish","format-standard","hentry","category-science","tag-medicine","tag-neuroscience"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/218293","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/17"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=218293"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/218293\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=218293"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=218293"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=218293"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=218293"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}