PMID- 36494916 OWN - NLM STAT- MEDLINE DCOM- 20230405 LR - 20230503 IS - 1476-5381 (Electronic) IS - 0007-1188 (Linking) VI - 180 IP - 9 DP - 2023 May TI - Non-neuronal TRPA1 encodes mechanical allodynia associated with neurogenic inflammation and partial nerve injury in rats. PG - 1232-1246 LID - 10.1111/bph.16005 [doi] AB - BACKGROUND AND PURPOSE: 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. 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 were analysed in cultured rat Schwann cells. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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. CI - (c) 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. FAU - De Logu, Francesco AU - De Logu F AUID- ORCID: 0000-0001-8360-6929 AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - De Siena, Gaetano AU - De Siena G AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Landini, Lorenzo AU - Landini L AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Marini, Matilde AU - Marini M AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Souza Monteiro de Araujo, Daniel AU - Souza Monteiro de Araujo D AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Albanese, Valentina AU - Albanese V AD - Department of Environmental and Prevention Sciences - DEPS, University of Ferrara, Ferrara, Italy. FAU - Preti, Delia AU - Preti D AD - Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara, Italy. FAU - Romitelli, Antonia AU - Romitelli A AUID- ORCID: 0000-0003-2495-8769 AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Chieca, Martina AU - Chieca M AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Titiz, Mustafa AU - Titiz M AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Iannone, Luigi F AU - Iannone LF AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Geppetti, Pierangelo AU - Geppetti P AUID- ORCID: 0000-0003-3797-8371 AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. FAU - Nassini, Romina AU - Nassini R AUID- ORCID: 0000-0002-9223-8395 AD - Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230107 PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (TRPA1 Cation Channel) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) RN - UKW89XAX2X (hydroxypropyl methacrylate) RN - 0 (Reactive Oxygen Species) RN - 0 (Transient Receptor Potential Channels) RN - 0 (TRPA1 protein, human) RN - 0 (Trpa1 protein, mouse) RN - 0 (Trpa1 protein, rat) SB - IM MH - Humans MH - Rats MH - Mice MH - Animals MH - Hyperalgesia MH - TRPA1 Cation Channel MH - Neurogenic Inflammation MH - Calcitonin Gene-Related Peptide/metabolism MH - Reactive Oxygen Species MH - *Transient Receptor Potential Channels MH - *Peripheral Nervous System Diseases OTO - NOTNLM OT - Schwann cells OT - TRPA1 OT - nerve injury OT - neurogenic inflammation OT - oxidative stress EDAT- 2022/12/11 06:00 MHDA- 2023/04/05 06:42 CRDT- 2022/12/10 01:03 PHST- 2022/11/11 00:00 [revised] PHST- 2022/07/30 00:00 [received] PHST- 2022/12/03 00:00 [accepted] PHST- 2023/04/05 06:42 [medline] PHST- 2022/12/11 06:00 [pubmed] PHST- 2022/12/10 01:03 [entrez] AID - 10.1111/bph.16005 [doi] PST - ppublish SO - Br J Pharmacol. 2023 May;180(9):1232-1246. doi: 10.1111/bph.16005. Epub 2023 Jan 7.