Pharmacological elevations of AEA in an arthritic rat were shown to suppress hypersensitivity of afferent nociceptors
and elevated pain thresholds by a process containing CB1 and TRPV1 channels (15).
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.
These changes promote the reduction of activation threshold and amplify the response of nociceptors
that innervate the damaged tissue (Woolf, 2010).
In transduction, nociceptors
containing special molecular proteins respond to noxious modalities, such as thermal, mechanical, or chemical stimuli, and trigger nerve impulses in the nociceptive nerve fibers (nerves dedicated to pain sensation).
When an injury occurs in a body of a vertebrate, specialized receptors, known as nociceptors
, are responsible to detect the damage.
More specifically, the ophthalmic division (V1) of the trigeminal nerve innervates dural and pial blood vessel nociceptors
that, when activated, cause a release of vasoactive neuropeptides such as substance P, calcitonin gene-related peptide, and neurokinin A which in turn cause increased cerebral blood flow, release of proinflammatory factors, and a reaction called neurogenic inflammation .
Heat pain activates AS or C nociceptors
depending on the intensity of the stimulus and whether the skin is heated at a rapid or a slow rate, respectively.
Nociceptive pain is pain that occurs from threatened or actual damage to non-neural tissue and is due to the activation of nociceptors
During this process there is a release of inflammatory mediators that sensitize peripheral nociceptors
, thus reducing the threshold of mechanic stimulation (28).
The gene encodes instructions for making a protein that helps pain-sensing nerve cells, called nociceptors
sensitizes peptidergic nociceptors
, leading to neuropathic pain with allodynia and hyperalgesia
Spinal wind-up is the spinal cord's expansion of signals from peripheral nociceptors
associated with C-fibers.