PPAR[gamma] Agonists Attenuate Trigeminal Neuropathic Pain.Lyons, Danielle N. PhD; Zhang, Liping PhD; Danaher, Robert J. PhD; Miller, Craig S. DMD; Westlund, Karin N. PhDClinical Journal of Pain: Post Acceptance: May 16, 2017 doi: 10.1097/AJP.0000000000000509 Original Article: PDF Only Abstract The aim of this study is to investigate the role of peroxisome proliferator-activated receptor-gamma isoform (PPAR[gamma]), in trigeminal neuropathic pain utilizing a novel mouse trigeminal inflammatory compression (TIC) injury model. The study determined that the PPAR[gamma] nuclear receptor plays a significant role in trigeminal nociception transmission, evidenced by: (1) Intense PPAR[gamma] 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 PPAR[gamma] 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 PPAR[gamma] 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. This is the first study localizing PPAR[gamma] immunoreactivity throughout the brainstem trigeminal sensory nucleus caudalis (spV) and its increase three weeks after TIC nerve injury. This is also the first study to demonstrate that activation of PPAR[gamma] 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 PPAR[gamma] for treatment of patients suffering from orofacial neuropathic pain. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.