Physiology of Pain

By Prof. Vajira Weerasinghe



     A thorough understanding of the physiological basis of pain is essential for planning proper management strategies for patients with acute or chronic pain.

     The scientific study of pain starts with its definition. The English word 'pain' probably derives from Old French (peine), Latin (poena - meaning punishment pain), or Ancient Greek (poine - a word more related to penalty), or a combination of all three. Since the perception and tolerance of pain varies widely from individual to individual, ‘pain’ is a difficult word to define. As it is a very individual experience, only the person who is experiencing pain can describe it properly. Patients use different words to describe pain and they have their own description of pain. It is customary to find many words in each language, which describe the experience of pain. However, an international definition is necessary to have a consensus among those interested in carrying out research work and for those involved in pain management.

     The current IASP (International Association for the Study of Pain) definition of pain states that “pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”

     Pain is primarily defined as a sensation, which is termed “nociception.” This implies that there are stimuli, receptors and a well-defined ascending sensory pathway for pain. However, pain is not just a sensation but it has a strong emotional component, which makes it unpleasant.

     It is a subjective experience and is protective in nature. Experience of pain is modified by developmental, behavioral, personality and cultural factors. Pain is a symptom rather than a sign. However, painful experiences are associated with signs such as crying, sweating, increased heart rate, raised blood pressure and behavioral changes.


Nociception and Pain Pathway

     Pain is usually described as fast pain and slow pain. This is due to the type of fiber, which transmits pain impulses. Fast pain is carried by thin myelinated A delta fiber which has a conduction velocity of about 20 m/s whereas, slow pain is carried by unmyelinated C fiber which has a conduction velocity of about 1-2 m/s. Fast pain is acute, pricking in nature, well localized and of short duration. On the other hand, slow pain is chronic and throbbing in nature, poorly localized and of long duration. Sometimes pain can be felt even when there are no stimuli, e.g. phantom limb pain in an amputee. On the other hand, there could be situations when pain is not felt even when a noxious stimulus is present, e.g. a soldier in a battlefield or a sportsman in an arena. Pain can also be due to a stimulus, which does not usually provoke pain, e.g. touch. This phenomenon is known as allodynia. 

     There are three types of pain, viz. nociceptive pain, neuropathic pain and psychogenic pain. Nociceptive pain is due to noxious stimuli activating pain nerve endings, thus causing an action potential to travel through the ascending pain pathways. Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the nervous system. If there is no definitive stimulus or definitive lesion, psychogenic pain will result.

     Practically any stimulus, if it is too strong, could cause pain. This will apply to physical stimuli (e.g. pressure), electrical, thermal (cold or hot) or chemical stimuli (e.g. H+, lactic acid, K+, histamine, bradykinin, acetylcholine and proteolytic enzymes). Prostaglandins are important chemicals in relation to visceral pain. They cannot directly stimulate pain nerve endings, however, they increase the sensitivity (or decrease the threshold) of pain nerve endings for other nociceptive stimuli.

      There are no specialized receptors for pain. Free nerve endings are sensitive to pain stimuli. Free nerve endings are distributed everywhere (in both somatic and visceral tissues).

     Nerve pathways carrying pain signals enter the spinal cord through dorsal roots. The first synapse is present in the dorsal horn of the spinal cord at an area known as substantia gelatinosa. Then the second order neurons ascend up through the lateral spinothalamic tracts to the central areas giving rise to pain perception. Unlike other general sensations, pain perception occurs at different levels. The thalamus is an important centre of pain perception. The lesions of the thalamus produce severe type of pain known as ‘thalamic pain.’ The sensory cortex is necessary only for the localization of pain. Other subcortical areas, which are important for pain perception, are the reticular formation, the limbic areas and the hypothalamus.


Descending Pain Modulatory System

     Several lines of experimental evidence have shown the presence of a descending pain modulatory system. The discovery of morphine receptors in certain areas in the brainstem has indicated that there should be endogenous opioid peptides present internally to modulate the ascending pain signal. In other words, there are internally generated analgesic chemicals present in our body to naturally counteract the pain signal. Some of the examples of these opioid peptides are endorphines, enkephalins and dynorphins. The discovery of opioid peptides as pain modulators and the descending pathway associated with them revolutionized the way we conceived the mechanism of central processing of a pain signal.

     The original descending pathway discovered, was from the periaqueductal grey nucleus of the midbrain to the nucleus raphe magnus of the medulla and then down to the substantia gelatinosa of the spinal cord. Subsequently, many other descending pathways, which modulate (mainly inhibits) the ascending pain signal, were discovered. Although original research studies showed opioid peptides such as enkephalins to be the neurotransmitters in these pathways, later, even non-opioid substances were known to be involved in these pathways. At present, we consider that there is a powerful descending pain modulatory system, which could modulate the pain signal as it ascends up. Therefore, the final pain perception depends on the interaction between the ascending pain impulse transmitting tracts and the descending pain modulatory (inhibitory) tracts. This could form the basis of explanation for many situations where pain is felt (or not felt). For example, a soldier in the battlefield with noxious stimuli activating his pain nerve endings may not feel pain at all. On the other hand, there may be situations where pain could occur when there are no related noxious stimuli or ascending pain signal (e.g. phantom limb pain). Therefore, pain perception is different to any other general sensation.


Gate Control Theory

     Although this picture is adequate to explain many of the situations where pain perception occurs, there are still other situations where explanations cannot be formulated. One such situation is how pain could be relieved very quickly, for example, by massaging a painful area. In order to explain this situation, we have to resort to pain theories which were used before opioids were discovered. Most of the pain theories are now outdated, however, one such theory is still applicable and is known as the “Gate control theory.” This theory was first put forward by P.D. Wall and R. Melzack in 1965. This explains how pain can be relieved very quickly by a neural mechanism. According to this theory, there is an interaction between the inputs of pain fibers and touch fibers at the spinal cord level in the form of a ‘gating mechanism.’ When the pain fiber alone is stimulated, gate will be opened and the pain is felt. However, when the pain and the touch fibers are stimulated together, gate will be closed and the pain is not felt. This theory, when it was first described, became very popular and provided the basis for various methods of pain relief such as massaging a painful area, applying irritable substances to a painful area (counter-irritation), Transcutaneous Electrical Nerve Stimulation (TENS) and even acupuncture. However later, the proponents of the gate control theory could not substantiate the mechanism of how this interaction occurs. However, recent discoveries of pain pathway such as finding of wide dynamic range cells have proved this theory is correct in explaining how pain could be relived very quickly using a neural mechanism.



      The above description of physiological mechanisms of pain shows that pain is not just a sensation but also a more complex phenomenon; it can be blocked at many places; chemicals play an important role in causing pain as well as in reducing pain, and neural mechanisms also play a role in pain interactions. This complex nature of pain perception makes it a very difficult entity to control.



Justin DM, ed. Pain 2005-An updated Review: Refresher course syllabus. Seattle: IASP Press; 2005.

Melzack R, Wall P. The Challenge of Pain. New York: Basic Books; 1983.

Mogil J, ed. Pain 2010-An Updated Review: Refresher Course Syllabus. Seattle: IASP Press; 2010.

Patel NB. Physiology of Pain. In:  Kopf A, Patel NB, editors. Guide to Pain Management in Low-Resource Settings. Seattle: IASP press; 2010.




Sri Lanka Association for the Study of Pain

The Sri Lankan Chapter of the International Association for the Study of Pain

© January 2014. Sri Lanka Association for the Study of Pain (SLASP). All Rights Reserved.

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̃ Pain: An Overview

̃ Physiology of Pain

̃ Pharmacological Management of Pain

̃ Neuropathic Pain

̃ Abdominal Pain

̃ Orofacial Pain: An Overview

̃ Pain: Psychological Correlates

̃ Assessment of Pain

̃ Management of Acute Post-Surgical Pain

̃ Management of Pain in Obstetrics

̃ Management of Musculoskeletal Pain and Chronic Pain Syndromes

̃ Management of Pain in Children

̃ Management of Pain in Neonates

̃ Management of Acute Pain in Trauma

̃ Management of Cancer Pain

̃ Management of Headache




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