Non-neuronal TRPA1 encodes mechanical allodynia evoked by neurogenic
inflammation and partial nerve injury in rats
Abstract
Background and Purpose. The proalgesic transient receptor potential
(TRP) ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary
sensory neurons, has been implicated in various pain models in mice.
However, evidence in rats indicates that TRPA1 conveys nociceptive
signals elicited by channel agonists but not those associated with
tissue inflammation or nerve injury. Here, in rats, we explored the
TRPA1 role in mechanical allodynia associated with neurogenic
inflammation and moderate (partial sciatic nerve ligation, pSNL) or
severe (chronic constriction injury, CCI) sciatic nerve injury.
Experimental Approach. Acute nociception and mechanical hypersensitivity
associated with neurogenic inflammation and sciatic nerve injury (pSNL
and CCI) were investigated in rats with TRPA1 pharmacological antagonism
or genetic silencing. TRPA1 presence and function was analyzed in
cultured rat Schwann cells. Key Results. Hind paw mechanical allodynia
(HPMA), but not acute nociception, evoked by local injection of the TRP
vanilloid 1 (TRPV1) agonist, capsaicin, or the TRPA1 agonist, allyl
isothiocyanate, was mediated by calcitonin gene related peptide (CGRP)
released from peripheral nerve terminals. CGRP-evoked HPMA was sustained
by a reactive oxygen species (ROS)-dependent TRPA1 activation, probably
in Schwann cells. HPMA evoked by pSNL, but not that evoked by CCI, was
mediated by ROS and TRPA1 without the involvement of CGRP. Conclusions
and Implications. As found in mice, TRPA1 mediates mechanical allodynia
associated with neurogenic inflammation and moderate nerve injury in
rats. The channel implication in mechanical hypersensitivity following
inflammation and partial nerve damage is a common rodent feature and
might be explored in humans.