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Pioglitazone attenuates tactile allodynia and thermal hyperalgesia in mice subjected to peripheral nerve injury.

Abstract
To clarify the role of peroxisome proliferator activated receptor gamma (PPARgamma) in neuropathic pain, we examined the effect of pioglitazone, a PPARgamma 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. PPARgamma 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 PPARgamma 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-alpha 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 PPARgamma stimulation.
AuthorsTakehiko Maeda, Norikazu Kiguchi, Yuka Kobayashi, Masanobu Ozaki, Shiroh Kishioka
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 108 Issue 3 Pg. 341-7 (Nov 2008) ISSN: 1347-8613 [Print] Japan
PMID19008646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 2-chloro-5-nitrobenzanilide
  • Analgesics
  • Anilides
  • Inflammation Mediators
  • Interleukin-6
  • PPAR gamma
  • Thiazolidinediones
  • Tumor Necrosis Factor-alpha
  • pioglitazone
Topics
  • Adipocytes (drug effects, metabolism)
  • Analgesics (pharmacology)
  • Anilides (pharmacology)
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal (drug effects, metabolism)
  • Hot Temperature
  • Hyperalgesia (etiology, metabolism, prevention & control)
  • Inflammation Mediators (metabolism)
  • Interleukin-6 (metabolism)
  • Ligation
  • Male
  • Mice
  • Mice, Inbred ICR
  • PPAR gamma (agonists, metabolism)
  • Pain Measurement
  • Posterior Horn Cells (drug effects, metabolism)
  • Sciatic Nerve (surgery)
  • Sciatic Neuropathy (complications, drug therapy, metabolism)
  • Thiazolidinediones (pharmacology)
  • Time Factors
  • Touch
  • Tumor Necrosis Factor-alpha (metabolism)

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