PPARγ Agonists Attenuate Trigeminal Neuropathic Pain

Danielle N. Lyons, Liping Zhang, Robert J. Danaher, Craig S. Miller, Karin N. Westlund

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Objectives: The aim of this study is to investigate the role of peroxisome proliferator-activated receptor-gamma isoform (PPARγ), in trigeminal neuropathic pain utilizing a novel mouse trigeminal inflammatory compression (TIC) injury model. Results: The study determined that the PPARγ nuclear receptor plays a significant role in trigeminal nociception transmission, evidenced by: 1) Intense PPARγ immunoreactivity is expressed 3 weeks after TIC nerve injury in the spinal trigeminal caudalis, the termination site of trigeminal nociceptive nerve fibers. 2) Systemic administration of a PPARγ agonist, pioglitazone (PIO), attenuates whisker pad mechanical allodynia at doses of 300 mg/kg i.p. and 600 mg/kg p.o. 3) Administration of a PPARγ antagonist, GW9662 (30 mg/kg i.p.), prior to providing the optimal dose of PIO (300 mg/kg i.p.) blocked the analgesic effect of PIO. Discussion: This is the first study localizing PPARγ immunoreactivity throughout the brainstem trigeminal sensory spinal nucleus (spV) and its increase three weeks after TIC nerve injury. This is also the first study to demonstrate that activation of PPARγ attenuates trigeminal hypersensitivity in the mouse TIC nerve injury model. The findings presented here suggest the possibility of utilizing the FDA approved diabetic treatment drug, PIO, as a new therapeutic that targets PPARγ for treatment of patients suffering from orofacial neuropathic pain.

Original languageEnglish
Pages (from-to)1071-1080
Number of pages10
JournalClinical Journal of Pain
Issue number12
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.


  • PPARγ
  • immunoreactivity
  • mechanical threshold
  • mice
  • spV
  • trigeminal inflammatory compression (TIC) injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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