Neuronal Cell Mechanisms of Pain

Pain is a distressful feeling that is frequently caused by intense or damaging chemical, thermal or mechanical stimuli. It can also occur without tissue damage or injury, although the patient makes reference to it. Pain is one of the body's most important communication tools, and a protective mechanism by which the body responds to noxious or harmful stimuli. The cascade of molecular events that culminate in the experience of pain in an individual is a complex neural phenomenon in which inordinate (excess) noxious peripheral stimuli are processed.

The work discussed comprehensively the current knowledge and the mechanistic understanding that underlies pain and analgesia, as well as the clinical correlations.

The strategy for the narrative review was carried out in works published in journals and other materials using original research articles, review articles, case reports, and standard pharmacology and pain text books. Electronic databases viz. scopus, science direct, pubmed, medline, and directory of open access journals were searched for relevant articles. Research works on the mechanisms of pain were identified for selection. Articles and works identified were those written in English and published between the period (1999 - 2020). Literature searches also included the scanning of references of journal articles.

Over one hundred and seventy-five journal articles and other works were identified. Many of the studies had the same titles. Eleven materials consulted were non-journal articles and text books, while 22 articles were extracted and reviewed after screening of the titles and abstracts, and in consonance with the selection criteria.The multi-stage biochemical and physiological processes transform nociceptive information (excess energy) generated from the primary afferent nerve fibres (first order neurones) - nociceptors (C-fibres and Aδ-fibres) in the periphery into electrical energy or pain impulses. The electrical impulses are then conducted by the axons of the first order neurones and terminate (or synapse) with intrinsic dorsal horn neurones (the first relay station in the transmission of nociceptive signals from the periphery to the brain), and the upper part of the spinal cord (substantia gelatinosa), from where axons of the second order neurones in the Rexed laminae receive the primary afferent input, and further propagate the signals to the higher brain centres (e.g., sub-cortical and cortical structures) by crossing the midline at the anterior white commissure to the contralateral (opposite) side of the spinal cord via the spinothalamic tracts and other ascending pathways (e.g., spinoreticular and spinomesencephalic tracts). The second order neurones synapse in the ventral posterolateral nucleus of the thalamus, from where third order neurones arise and transmit the nociceptive signals to various anatomical regions of the cortex. The third order neurones project via the posterior limb of the internal capsule to terminate in the ipsilateral (on the same side) post-central gyrus (primary somatosensory cortex). The generation, transduction, transmission and ascent of these neuronal impulses to the higher centres are modulated by the descending control pain pathway (otherwise known as the efferent analgesic system), which is both inhibitory and facilitatory in function, and ultimately results in the experience of pain. Terminal nerve endings located at sites of tissue injury (or inflammation) exhibit exaggerated neuronal responses that cause increased cell membrane excitability, a condition referred to as peripheral sensitisation, as well as a heightened activity of the pain circuitry and pain signal processing in the central nervous system. These phenomena are responsible for the abnormal transmission of pain impulses and experience (e.g., hyperalgesia and allodynia) that accompany certain clinical conditions.

Clinical pain is a serious public health concern, and has a multiplicity of causes. The mechanistic understanding of pain is a step-wise complex biological event, which has provided insight to explore better therapeutic options with a view to improving the quality of life and living in individuals with clinical pain conditions.