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.

Background and purpose Migraine represents one of the major causes of disability worldwide and is more prevalent in women, it is also related to anxiety symptoms. Stress is a frequently reported trigger in migraine patients, such as sound stress, but the underlying mechanisms are not fully understood. However, it is known that patients with migraine have higher levels of plasma inflammatory cytokines and calcitonin gene-related peptide (CGRP). Stress mediated by unpredictable sound is already used as a model of painful sensitization, but migraine-like behaviors and sexual dimorphism have not yet been evaluated. This study characterized the nociception and anxiety-related symptoms after the induction of unpredictable sound stress in mice. Experimental approach C57BL/6 mice (20-30 g) were exposed to unpredictable sound stress for 3 days. Mainly, after 7 days of the last stress session mice developed hind paw, periorbital mechanical allodynia, grimacing pain behavior, anxiety-like, and reduced exploratory behavior. Key results These nociceptive and behavioral alterations detected in this model were shown mostly in female stressed mice. Besides, 7th-day post-stress nociception, these behaviors were consistently abolished by CGRP receptor antagonist olcegepant (BIBN4096BS, 100mg/kg by intraperitoneal route) until 3 h after treatment in stressed mice. In addition, we demonstrated an increase in levels of IL-6 and TNF-α and CGRP levels in stressed mice plasma, with female with higher levels when compared to male mice. Conclusions and implications This stress paradigm allows further preclinical investigation of mechanisms contributing to migraine pain, which appear to be distinct in male and female mice.