Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury
Takehiko MaedaNorikazu KiguchiYuka KobayashiMasanobu OzakiShiroh Kishioka
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2008 Volume 108 Issue 3 Pages 341-347

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Abstract

To clarify the role of peroxisome proliferator activated receptor γ (PPARγ) in neuropathic pain, we examined the effect of pioglitazone, a PPARγ agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 – 25 mg/kg, p.o.) once daily. PPARγ was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/kg, i.p.), a PPARγ antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-α and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARγ stimulation.

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© The Japanese Pharmacological Society 2008
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