Background and PurposeThe oxidant sensor transient receptor potential ankyrin 1 (TRPA1) channel expressed by Schwann cells (SCs) has recently been implicated in several models of neuropathic pain in rodents. Here we investigate whether the pro-algesic function of Schwann cell TRPA1 is not limited to mammals by exploring the role of TRPA1 in a model of chemotherapy-induced peripheral neuropathy (CIPN) in zebrafish larvae.Experimental ApproachWe used zebrafish larvae and a mouse model to test oxaliplatin-evoked nociceptive behaviours. We also performed a TRPA1 selective silencing in Schwann cells both in zebrafish larvae and mice to study their contribution in oxaliplatin-induced CIPN model.Key ResultsWe found that zebrafish larvae and zebrafish TRPA1 (zTRPA1)-transfected HEK293T cells respond to reactive oxygen species (ROS) with nociceptive behaviours and intracellular calcium increases, respectively. TRPA1 was found to be co-expressed with the Schwann cell marker, SOX10, in zebrafish larvae. Oxaliplatin caused nociceptive behaviours in zebrafish larvae that were attenuated by a TRPA1 antagonist and a ROS scavenger. Oxaliplatin failed to produce mechanical allodynia in mice with Schwann cell TRPA1 selective silencing (Plp1+-Trpa1 mice). Comparable results were observed in zebrafish larvae where TRPA1 selective silencing in Schwann cells, using the specific Schwann cell promoter myelin basic protein (MBP), attenuated oxaliplatin-evoked nociceptive behaviours.Conclusion and ImplicationsThese results indicate that the contribution of the oxidative stress/Schwann cell/TRPA1 pro-allodynic pathway to neuropathic pain models seems to be conserved across the animal kingdom.

Schwann cell transient receptor potential ankyrin 1 (TRPA1) ortholog in zebrafish larvae mediates chemotherapy‐induced peripheral neuropathy / Bellantoni, Elisa; Marini, Matilde; Chieca, Martina; Gabellini, Chiara; Crapanzano, Erica Lucia; Souza Monteiro de Araujo, Daniel; Nosi, Daniele; Roschi, Lorenzo; Landini, Lorenzo; De Siena, Gaetano; Pensieri, Pasquale; Mastricci, Alessandra; Scuffi, Irene; Geppetti, Pierangelo; Nassini, Romina; De Logu, Francesco. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - ELETTRONICO. - 181:(2024), pp. 4859-4873. [10.1111/bph.17318]

Schwann cell transient receptor potential ankyrin 1 (TRPA1) ortholog in zebrafish larvae mediates chemotherapy‐induced peripheral neuropathy

Bellantoni, Elisa;Marini, Matilde;Chieca, Martina;Souza Monteiro de Araujo, Daniel;Nosi, Daniele;Roschi, Lorenzo;Landini, Lorenzo;De Siena, Gaetano;Pensieri, Pasquale;Mastricci, Alessandra;Scuffi, Irene;Geppetti, Pierangelo;Nassini, Romina;De Logu, Francesco
2024

Abstract

Background and PurposeThe oxidant sensor transient receptor potential ankyrin 1 (TRPA1) channel expressed by Schwann cells (SCs) has recently been implicated in several models of neuropathic pain in rodents. Here we investigate whether the pro-algesic function of Schwann cell TRPA1 is not limited to mammals by exploring the role of TRPA1 in a model of chemotherapy-induced peripheral neuropathy (CIPN) in zebrafish larvae.Experimental ApproachWe used zebrafish larvae and a mouse model to test oxaliplatin-evoked nociceptive behaviours. We also performed a TRPA1 selective silencing in Schwann cells both in zebrafish larvae and mice to study their contribution in oxaliplatin-induced CIPN model.Key ResultsWe found that zebrafish larvae and zebrafish TRPA1 (zTRPA1)-transfected HEK293T cells respond to reactive oxygen species (ROS) with nociceptive behaviours and intracellular calcium increases, respectively. TRPA1 was found to be co-expressed with the Schwann cell marker, SOX10, in zebrafish larvae. Oxaliplatin caused nociceptive behaviours in zebrafish larvae that were attenuated by a TRPA1 antagonist and a ROS scavenger. Oxaliplatin failed to produce mechanical allodynia in mice with Schwann cell TRPA1 selective silencing (Plp1+-Trpa1 mice). Comparable results were observed in zebrafish larvae where TRPA1 selective silencing in Schwann cells, using the specific Schwann cell promoter myelin basic protein (MBP), attenuated oxaliplatin-evoked nociceptive behaviours.Conclusion and ImplicationsThese results indicate that the contribution of the oxidative stress/Schwann cell/TRPA1 pro-allodynic pathway to neuropathic pain models seems to be conserved across the animal kingdom.
2024
181
4859
4873
Goal 3: Good health and well-being
Bellantoni, Elisa; Marini, Matilde; Chieca, Martina; Gabellini, Chiara; Crapanzano, Erica Lucia; Souza Monteiro de Araujo, Daniel; Nosi, Daniele; Rosc...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1402540
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