Neuropathic-like Nociception and Spinal Cord Neuroinflammation Are Dependent on the TRPA1 Channel in Multiple Sclerosis Models in Mice

Diéssica Padilha Dalenogare; Daniel Souza Monteiro de Araújo; Lorenzo Landini; Mustafa Titiz; Gaetano De Siena; Francesco De Logu; Pierangelo Geppetti; Romina Nassini; Gabriela Trevisan

doi:10.3390/cells12111511

Neuropathic-like Nociception and Spinal Cord Neuroinflammation Are Dependent on the TRPA1 Channel in Multiple Sclerosis Models in Mice

Cells. 2023 May 30;12(11):1511. doi: 10.3390/cells12111511.

Authors

Diéssica Padilha Dalenogare¹, Daniel Souza Monteiro de Araújo², Lorenzo Landini², Mustafa Titiz², Gaetano De Siena², Francesco De Logu², Pierangelo Geppetti², Romina Nassini², Gabriela Trevisan¹

Affiliations

¹ Graduated Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil.
² Clinical Pharmacology Unit, Department of Health Sciences, University of Florence, 50139 Florence, Italy.

Abstract

Background: Transient receptor potential ankyrin 1 (TRPA1) activation is implicated in neuropathic pain-like symptoms. However, whether TRPA1 is solely implicated in pain-signaling or contributes to neuroinflammation in multiple sclerosis (MS) is unknown. Here, we evaluated the TRPA1 role in neuroinflammation underlying pain-like symptoms using two different models of MS. Methods: Using a myelin antigen, Trpa1⁺^/+ or Trpa1^-^/- female mice developed relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) (Quil A as adjuvant) or progressive experimental autoimmune encephalomyelitis (PMS)-EAE (complete Freund's adjuvant). The locomotor performance, clinical scores, mechanical/cold allodynia, and neuroinflammatory MS markers were evaluated. Results: Mechanical and cold allodynia detected in RR-EAE, or PMS-EAE Trpa1⁺^/+ mice, were not observed in Trpa1^-^/- mice. The increased number of cells labeled for ionized calcium-binding adapter molecule 1 (Iba1) or glial fibrillary acidic protein (GFAP), two neuroinflammatory markers in the spinal cord observed in both RR-EAE or PMS-EAE Trpa1⁺^/+ mice, was reduced in Trpa1^-^/- mice. By Olig2 marker and luxol fast blue staining, prevention of the demyelinating process in Trpa1^-^/- induced mice was also detected. Conclusions: Present results indicate that the proalgesic role of TRPA1 in EAE mouse models is primarily mediated by its ability to promote spinal neuroinflammation and further strengthen the channel inhibition to treat neuropathic pain in MS.

Keywords: allodynia; astrocyte; microglia; neuroinflammation; oligodendrocyte; pain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Encephalomyelitis, Autoimmune, Experimental* / metabolism
Female
Hyperalgesia / drug therapy
Mice
Multiple Sclerosis* / metabolism
Neuralgia* / drug therapy
Neuroinflammatory Diseases
Nociception
Spinal Cord / metabolism
TRPA1 Cation Channel / metabolism
Transient Receptor Potential Channels* / metabolism

Substances

TRPA1 Cation Channel
Transient Receptor Potential Channels

Grants and funding

Fellowships from the Conselho Nacional de Desenvolvimento Científico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) are also acknowledged. Diéssica Padilha Dalenogare fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [process #88882.428089/2019-01] and Programa Institucional de Internacionalização CAPES [process #88887.374020/2019-00]. G.T. is the recipient of a fellowship from the CNPq [process #303531/2020-7], L’ORÉAL–ABC–UNESCO Para Mulheres na Ciência, 2016 and Prêmio Capes de Teses–Ciências Biológicas II, CAPES, 2014 [process #23038.006930/2014/59]. G.T. is the recipient of a research grant from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [process #21/2551-0001935-2]. This work was also supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 835286) (P.G.).