Elisa Bellantoni, Matilde Marini, Martina Chieca, Chiara Gabellini, Erica Lucia Crapanzano, Daniel Souza Monteiro de Araujo, Daniele Nosi, Lorenzo Roschi, Lorenzo Landini, Gaetano De Siena, Pasquale Pensieri, Alessandra Mastricci, Irene Scuffi, Pierangelo Geppetti, Romina Nassini, Francesco De Logu
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引用次数: 0
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.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.