Non‐neuronal TRPA1 encodes mechanical allodynia associated with neurogenic inflammation and partial nerve injury in rats

Autor: Francesco De Logu, Gaetano De Siena, Lorenzo Landini, Matilde Marini, Daniel Souza Monteiro de Araujo, Valentina Albanese, Delia Preti, Antonia Romitelli, Martina Chieca, Mustafa Titiz, Luigi F. Iannone, Pierangelo Geppetti, Romina Nassini
Rok vydání: 2023
Předmět:
Zdroj: British Journal of Pharmacology. 180:1232-1246
ISSN: 1476-5381
0007-1188
DOI: 10.1111/bph.16005
Popis: The pro-algesic transient receptor potential 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 activators, but not those associated with tissue inflammation or nerve injury. Here, in rats, we explored the TRPA1 role in mechanical allodynia associated with stimulation of peptidergic primary sensory neurons (neurogenic inflammation) and moderate (partial sciatic nerve ligation, pSNL) or severe (chronic constriction injury, CCI) sciatic nerve injury.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 were analysed in cultured rat Schwann cells.Hind paw mechanical allodynia (HPMA), but not acute nociception, evoked by local injection of capsaicin or allyl isothiocyanate, the TRP vanilloid 1 (TRPV1) or the TRPA1 activators was mediated by CGRP released from peripheral sensory nerve terminals. CGRP-evoked HPMA was sustained by a 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.As found in mice, TRPA1 mediates mechanical allodynia associated with neurogenic inflammation and moderate nerve injury in rats. The channel contribution to mechanical hypersensitivity is a common feature in rodents and might be explored in humans.
Databáze: OpenAIRE
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