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Open Access 01-12-2011 | Research

Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain

Authors: Yasutaka Kakiuchi, Jun Nagai, Mari Gotoh, Harumi Hotta, Hiromu Murofushi, Tomoyo Ogawa, Hiroshi Ueda, Kimiko Murakami-Murofushi

Published in: Molecular Pain | Issue 1/2011

1. Abstract

Background

Cyclic phosphatidic acid (cPA) is a structural analog of lysophosphatidic acid (LPA), but possesses different biological functions, such as the inhibition of autotaxin (ATX), an LPA-synthesizing enzyme. As LPA is a signaling molecule involved in nociception in the peripheral and central systems, cPA is expected to possess analgesic activity. We characterized the effects of cPA and 2-carba-cPA (2ccPA), a chemically stable cPA analog, on acute and chronic pain.

Results

(1) The systemic injection of 2ccPA significantly inhibited somato-cardiac and somato-somatic C-reflexes but not the corresponding A-reflexes in anesthetized rats. (2) 2ccPA reduced sensitivity measured as the paw withdrawal response to electrical stimulation applied to the hind paws of mice through the C-fiber, but not Aδ or Aβ. (3) In mice, pretreatment with 2ccPA dose-dependently inhibited the second phase of formalin-induced licking and biting responses. (4) In mice, pretreatment and repeated post-treatments with 2ccPA significantly attenuated thermal hyperalgesia and mechanical allodynia following partial ligation of the sciatic nerve. (5) In rats, repeated post-treatments with 2ccPA also significantly attenuated thermal hyperalgesia and mechanical allodynia following chronic sciatic nerve constriction.

Conclusions

Our results suggest that cPA and its stable analog 2ccPA inhibit chronic and acute inflammation-induced C-fiber stimulation, and that the central effects of 2ccPA following repeated treatments attenuate neuropathic pain.

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Title: Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain
Authors: Yasutaka Kakiuchi
Jun Nagai
Mari Gotoh
Harumi Hotta
Hiromu Murofushi
Tomoyo Ogawa
Hiroshi Ueda
Kimiko Murakami-Murofushi
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2011
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-7-33

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain

1. Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

1. Abstract

Background

Results

Conclusions

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