A few decades ago the task of developing "subtype" specific VGSC-blocking drugs would have been unrealistic, given our limited understanding of the complex interplay behind nociceptor
Neurogenic inflammation is defined as a peripheral inflammatory response that is mediated antidromically through nociceptors
. (9) This phenomenon is caused by the release of proinflammatory mediators peripherally via antidromic mechanisms to create a localized inflammatory response in the receptive field of the affected nociceptor
Furthermore, the definition suggests that pain is always subjective: "It is unquestionably a sensation in a part or parts of the body, but it is also always unpleasant and therefore also an emotional experience." The definition also includes "Activity induced in the nociceptor
and nociceptive pathways by a noxious stimulus is not pain, which is always a psychological state, even though we may well appreciate that pain most often has a proximate physical cause." The definition of pain is important because it emphasizes that pain is a multidimensional problem and thus the ultimate cure for pain must target all underlying pathophysiology and contributing psychosocial factors.
signals back down the spinal cord, through descending axons, to modulate the sensitivity of nociceptor
Neuropathic mechanisms that might be at work in PIFP include nociceptor
sensitization, phenotypic changes and ectopic activity from the nociceptors
, central sensitization possibly maintained by ongoing activity from initially damaged peripheral tissues, sympathetic abnormal activity, alteration of segmental inhibitory control, or hyperactivity or hypoactivity of descending controls.
stimulation triggers action potentials in sensory nerve fibres that transmit impulses to the dorsal horn of the spinal cord.
Several studies have indicated that the mechanisms of neuropathic pain originate from an increase in primary afferent nociceptor
firing; consequently, this may cause ectopic discharge, or because of decreases the inhibition of neuronal activity and an alternation of the central process .
Torebjork, "Psychophysical evidence of nociceptor
sensitization in vulvar vestibulitis syndrome," Pain, vol.
Afferent activity in nociceptor
fibres dislodges the central magnesium ion from the NMDA receptor, therefore allowing calcium influx into the cell.
To verify the analgesic effect, a sensibility test was conducted by lightly pressing a needle to the lip of each fish, where nociceptor
fibres are usually found (Sneddon, 2003).
Psychophysical evidence of nociceptor
sensitization in vulvar vestibulitis syndrome.