Considerable progress has been made in understanding the molecular and physiological intricacies behind
nociceptor firing.
Convergence of neural tracts is a basic architectural construct of the nervous system and the dorsal horn is where
nociceptors of somatic and visceral origin are known to converge.
In particular, scientists believe that
nociceptor cells release the peptide to trigger the cord nerve cells that pass pain signals on to the brain.
Nociceptor signals, following acute injury, undergo complex processing in the dorsal horn of the spinal cord (as explained by Melzack and Wall's gate control theory (12)).
TRPV4 is also involved in the osmolar detection of
nociceptor enhancing the production of prostaglandin E2 that is a hyperalgesic inflammatory mediator; thus, the role of TRPV4 is diverse and also is a pain signaling transducer [30].
The vulvar allodynia that is elicited by mechanical and thermal (heat and cold) low threshold stimuli is probably associated with local peripheral sensitization of both polymodal C-mechanoheat
nociceptors and normally mechanoinsensitive C-nociceptors [33-35].
The anti-inflammatory action in the peripheral tissues occurs through antagonising the release of inflammatory mediators such as histamine, cytokines and serotonin which in turn excite
nociceptors. [31]
The ability of fish to feel pain is sustained by the presence of
nociceptors (delta A and C fibres) identical to those of mammals, connected to a comparative brain structure (Sneddon, 2003).
Peripheral sensitization of
nociceptors has been demonstrated as a possible mechanism of vulvodynia.
How this multitude of cascades mediates
nociceptor sensitization and pain is only beginning to be understood.
[2] Current studies regarding KOA pain mechanism mostly focus on the following three aspects: (i) synovial inflammation: pro-inflammatory cytokines such as histamine, prostaglandins, leukotriene, neuropeptides may activate
nociceptor to induce pain; (ii) ostealgia: subchondral bone and marrow vessels and nerves exposure caused by KOA articular surface cartilage denudation may also lead to pain; (iii) decreased pain threshold: chronic pain in KOA demonstrates a decreased pain threshold, which can give rise to an increased pain intensity by pain stimulation in the same intensity (hyperalgesia) and even by non-painful stimulation (allodynia).
There are two divided models of PHN: the "irritable
nociceptor" model and "deafferentation" model.
This redundancy is evident at a danger detection level, whereby a range of receptors are responsive to stimuli in the noxious range, (22) at a spinal level, causing multiple pathways and modulatory interneurons to contribute to spinal
nociceptor discharge, (60) and at a brain level, where multiple feelings and systems can drive protective behavior.
High-concentration capsaicin activates TRPV1 channels by overstimulating the
nociceptors, resulting in the defunctionalization of the
nociceptor nerve fibers and thereby reducing spontaneous nerve activity, leading to a loss of responsiveness.
