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

Ivan J M Bonet; Dionéia Araldi; Oliver Bogen; Jon D Levine

doi:10.1016/j.jpain.2020.11.004

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

Journal article

Peer reviewed

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

Ivan J M Bonet, Dionéia Araldi, Oliver Bogen and Jon D Levine

The journal of pain, Vol.22(5), pp.498-508

05/01/2021

DOI: 10.1016/j.jpain.2020.11.004

PMID: 33232830

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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 E , 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.

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

Neuralgia - etiology

Neuralgia - physiopathology

Oxaliplatin - adverse effects

Paclitaxel - adverse effects

Pain Threshold - physiology

Rats

Rats, Sprague-Dawley

Details

Title: Subtitle: Involvement of TACAN, a Mechanotransducing Ion Channel, in Inflammatory But Not Neuropathic Hyperalgesia in the Rat
Creators: Ivan J M Bonet - University of California, San Francisco
Dionéia Araldi - University of California, San Francisco
Oliver Bogen - University of California, San Francisco
Jon D Levine - Departments of Medicine and Oral & Maxillofacial Surgery, and Division of Neuroscience, UCSF Pain and Addiction Research Center, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, California. Electronic address: Jon.Levine@ucsf.edu
Resource Type: Journal article
Publication Details: The journal of pain, Vol.22(5), pp.498-508
DOI: 10.1016/j.jpain.2020.11.004
PMID: 33232830
ISSN: 1526-5900
eISSN: 1528-8447
Grant note: R01 CA250017 / NCI NIH HHS R01 AR063312 / NIAMS NIH HHS R01 AR075334 / NIAMS NIH HHS
Language: English
Date published: 05/01/2021
Academic Unit: Neuroscience and Pharmacology
Record Identifier: 9985177942102771

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