Involvement of TACAN, a Mechanotransducing Ion Channel, in Inflammatory But Not Neuropathic Hyperalgesia in the Rat.

Abstract

TACAN (Tmem120A), a mechanotransducing ion channel highly expressed in a subset of nociceptors, has recently been shown to contribute to detection of noxious mechanical stimulation. In the present study we evaluated its role in sensitization to mechanical stimuli associated with preclinical models of inflammatory and chemotherapy-induced neuropathic pain (CIPN). Intrathecal administration of an oligodeoxynucleotide antisense (AS-ODN) to TACAN mRNA attenuated TACAN protein expression in rat dorsal root ganglia (DRG). While TACAN AS-ODN produced only a modest increase in mechanical nociceptive threshold, it markedly reduced mechanical hyperalgesia produced by intradermal administration of prostaglandin E2, tumor necrosis factor alpha, and low molecular weight hyaluronan, and systemic administration of lipopolysaccharide, compatible with a prominent role of TACAN in mechanical hyperalgesia produced by inflammation. In contrast, TACAN AS-ODN had no effect on mechanical hyperalgesia associated with CIPN produced by oxaliplatin or paclitaxel. Our results provide evidence that TACAN plays a role in mechanical hyperalgesia induced by pronociceptive inflammatory mediators, but not CIPN, compatible with multiple mechanisms mediating mechanical nociception, and sensitization to mechanical stimuli in preclinical models of inflammatory versus CIPN. PERSPECTIVE: We evaluated the role of TACAN, a mechanotransducing ion channel in nociceptors, in preclinical models of inflammatory and CIPN. Attenuation of TACAN expression reduced hyperalgesia produced by inflammatory mediators but had not chemotherapeutic agents. Our findings support the presence of multiple mechanotransducers in nociceptors.

• Authors: Ivan J M Bonet, Dionéia Araldi, Oliver Bogen, Jon D Levine
• Journal: The journal of pain (J Pain) Vol. 22 Issue 5 Pg. 498-508 (05 2021) ISSN: 1528-8447 [Electronic] United States
• PMID: 33232830 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Ion Channels
• Oxaliplatin
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (adverse effects)
• Disease Models, Animal
• Ganglia, Spinal (physiology)
• Hyperalgesia (physiopathology)
• Inflammation (complications)
• Ion Channels (pharmacology)
• Male
• Mechanotransduction, Cellular (physiology)
• Neuralgia (chemically induced, etiology, physiopathology)
• Oxaliplatin (adverse effects)
• Paclitaxel (adverse effects)
• Pain Threshold (physiology)
• Rats
• Rats, Sprague-Dawley