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Open Access 01-12-2008 | Research

HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity

Authors: Samer R Eid, Eric D Crown, Eric L Moore, Hongyu A Liang, Kar-Chan Choong, Shelley Dima, Darrell A Henze, Stefanie A Kane, Mark O Urban

Published in: Molecular Pain | Issue 1/2008

Abstract

Background

Safe and effective treatment for chronic inflammatory and neuropathic pain remains a key unmet medical need for many patients. The recent discovery and description of the transient receptor potential family of receptors including TRPV1 and TRPA1 has provided a number of potential new therapeutic targets for treating chronic pain. Recent reports have suggested that TRPA1 may play an important role in acute formalin and CFA induced pain. The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain.

Results

The in vitro potencies of HC-030031 versus cinnamaldehyde or allyl isothiocyanate (AITC or Mustard oil)-induced TRPA1 activation were 4.9 ± 0.1 and 7.5 ± 0.2 μM respectively (IC₅₀). These findings were similar to the previously reported IC₅₀ of 6.2 μM against AITC activation of TRPA1 [1]. In the rat, oral administration of HC-030031 reduced AITC-induced nocifensive behaviors at a dose of 100 mg/kg. Moreover, oral HC-030031 (100 mg/kg) significantly reversed mechanical hypersensitivity in the more chronic models of Complete Freunds Adjuvant (CFA)-induced inflammatory pain and the spinal nerve ligation model of neuropathic pain.

Conclusion

Using oral administration of the selective TRPA1 antagonist HC-030031, our results demonstrated that TRPA1 plays an important role in the mechanisms responsible for mechanical hypersensitivity observed in inflammatory and neuropathic pain models. These findings suggested that TRPA1 antagonism may be a suitable new approach for the development of a potent and selective therapeutic agent to treat both inflammatory and neuropathic pain.

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Title: HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity
Authors: Samer R Eid
Eric D Crown
Eric L Moore
Hongyu A Liang
Kar-Chan Choong
Shelley Dima
Darrell A Henze
Stefanie A Kane
Mark O Urban
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2008
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-4-48

Keynote webinar | Spotlight on medication adherence

Springer Medicine

HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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