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. 2024 Dec;181(23):4859-4873.
doi: 10.1111/bph.17318. Epub 2024 Sep 5.

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

Elisa Bellantoni  1 , Matilde Marini  1 , Martina Chieca  1 , Chiara Gabellini  2 , Erica Lucia Crapanzano  2 , Daniel Souza Monteiro de Araujo  1 , Daniele Nosi  3 , Lorenzo Roschi  4 , Lorenzo Landini  1 , Gaetano De Siena  1 , Pasquale Pensieri  1 , Alessandra Mastricci  1 , Irene Scuffi  1 , Pierangelo Geppetti  1   5   6 , Romina Nassini  1 , Francesco De Logu  1
Affiliations

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

Elisa Bellantoni et al. Br J Pharmacol. 2024 Dec.

Abstract

Background and purpose: The 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 approach: We 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 results: We 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 implications: These 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.

Keywords: Schwann cells; nociceptive behaviours; oxaliplatin; oxidative stress; transient receptor potential ankyrin 1 (TRPA1).

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References

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