The process of nociceptionexplains how the body processes pain, and it begins when a stimulus stimulatesnociceptors, which are highly specialised primary sensory neurones foundprimarily in the skin, joints or organs such as the liver. The classification of nociceptorscan be derived into two categories; lightly myelinated A? fibers and unmyelinated C fibersand due to their difference in conduction velocity, the action potential of theA? fibers can travel at a rate ofaround 20m/s, whereas the C fibres conduct at slower speeds of around 2m/s(Fein 2014). C-fiber nociceptors respond poly-modally to thermal, mechanical,and chemical stimuli; and the A?-fiber nociceptors are of two types and respondto mechanical and mechano-thermal stimuli (Patel 2010).
(Lamont et al, 2000) explainhow A-fiber nociceptors are responsible for signaling ‘first pain,’ which canbe described as a ‘sharp, stinging, or pricking sensation’, it is also ‘localizedand transient, lasting only as long as the acute painful stimulus is activatingthe nociceptor’. In contrast, Lamont et al also explain that if a stimulus isof sufficient magnitude, C-fiber nociceptors are recruited and mediate ‘slowpain,’ which is ‘a more diffuse and persistent burning sensation extendingbeyond the termination of an acute painful stimulus’. The first stageof nociception is transduction, and is modulated by a number of chemicalsubstances produced when the cell is damaged. They influence the degree ofnerve activity and hence intensity of the pain sensation. The chemicalmediators released from the damaged cell include prostaglandin, serotonin whichis released from platelets and histamine released from mast cells (Patel 2010).The release of histamine as well as substance P causes vasodilation, aprotective mechanism which eventually promotes healing and protection againstinfection. An action potential is generated due to the presence of ion channelswhich are tuned to respond with a high threshold only to particular features of themechanical, thermal, and chemical environment (Ramsey et al, 2006). When thechannels are activated, depolarization of the membrane occurs due to voltagevoltage-dependent sodium and potassium channels and potassium ions.
The next stage is the transmission of pain, where the impulsetravels along the nociceptor axons to their cell bodies located in the dorsalroot ganglion in the spinal cord, and then to their central terminals in thedorsal horn, which is organized into different laminae. Lamina II is also known as thesubstantia gelatinosa and this extends from the trigeminal nucleus in themedulla, to the filum terminale at the caudal end of the spinal cord. (Steeds,2016). Most nociceptive A?- and C-fibres terminate superficially in laminaeI–II, with a smaller number reaching deeper laminae (Dickinson, 2008). Projectionneurons in the dorsal horn relay nociceptive inputs to higher centers in thebrain via five major ascending pathways, the main ascendingpathway being the spinothalamic tract located in the anterolateral whitematter of the spinal cord. Axons travelling in the lateral and medial spinothalamictracts terminate in their respective medial and lateral nuclei and from hereneurons project to the primary and secondary somatosensory cortices, theinsula, the anterior cingulate cortex and the prefrontal cortex, and theseareas are involved in the perception of pain.
Finally, the modulation of paininvolves changing or inhibiting transmission of pain impulses in the spinalcord. Excitatory neuropeptides including glutamate, aspartate andsubstance P can facilitate and amplify the pain signals in ascending projectionneurons. Similarly, endogenous (opioid, serotonergic and noradrenergic)descending analgesic systems serve to dampen the nociceptive response. Two important areas of thebrainstem are involved in reducing pain: the periaquaductal grey (PAG) and thenucleus raphe magnus (NRM), PAG (anti-nociceptor) neurons excite cells in theNRM that in turn project down to the spinal cord to block pain transmission bydorsal horn cells. Stimulation of the raphe nuclei produces a powerfulanalgesia and it is thought that the serotonin released by this stimulationactivates inhibitory interneurons even more powerfully than noradrenaline andthus blocks pain transmission