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
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Article info
Publication history
Published online: November 20, 2020
Accepted:
November 13,
2020
Received in revised form:
November 9,
2020
Received:
August 7,
2020
Footnotes
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.
Identification
Copyright
© 2020 by United States Association for the Study of Pain, Inc.
