Elsevier

The Journal of Pain

Volume 22, Issue 5, May 2021, Pages 498-508
The Journal of Pain

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

https://doi.org/10.1016/j.jpain.2020.11.004Get rights and content
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Highlights

  • Knocking down TACAN in DRG cells increases mechanical nociceptive threshold.

  • TACAN plays a crucial role in inflammatory mechanical hyperalgesia.

  • Chemotherapy-induced peripheral neuropathy is not dependent on TACAN.

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.

Keywords

TACAN
mechanical nociceptive threshold
hyperalgesia
CIPN

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Disclosures: All authors report no financial interests or potential conflicts of interest. This study was funded by National Institutes of Health (NIH) grants CA250017 and AR075334.