title: Spinal neuroimmune activation inhibited by repeated administration of pioglitazone in rats after L5 spinal nerve transection.
abstract: Neuroimmune activation contributes to the generation and maintenance of neuropathic pain after peripheral nerve injury. Peroxisome proliferator activated receptor gamma (PPAR-γ) agonists have potential neuroprotection. The current study aimed to determine the effects of a PPAR-γ agonist pioglitazone on mechanical hyperalgesia and neuroimmune activation in a rat model of neuropathic pain induced by L5 spinal nerve transection (SNT). Thirty-two rats were equally randomized into 4 groups: sham operation with vehicle; L5 SNT with vehicle or pioglitazone; or L5 SNT with pioglitazone and a PPAR-γ antagonist GW9662. Pioglitazone or vehicle was administered 1h before operation and continued daily to day 14 after operation. The paw pressure threshold (PPT) was measured before operation and on days 3, 7, 14 after operation. Glial fibrillary acidic protein (GFAP) expression, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 levels, and nuclear factor-kappa B (NF-κB) activity in the lumbar spinal cord were determined on day 14 after operation. The results displayed pioglitazone improved the mechanical hyperalgesia, and attenuated the astrocyte and NF-κB activation and the inflammatory cytokine upregulation in nerve-injured rats, which might be reversed by GW9662. In conclusion, pioglitazone ameliorates the mechanical hyperalgesia induced by L5 SNT via inhibiting the spinal neuroimmune activation in rats, suggesting spinal PPAR-γ signaling pathway may be involved in the pathogenesis of mechanical hyperalgesia.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Jia
authors.forename: Xing-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Qiu
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liu
authors.forename: Jin-Chun
authors.initials: JC
authors.lastname: Shen
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015213:Neuroimmunomodulation; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047495:PPAR gamma / Q000819:agonists*; D017288:Pain Threshold; D000077205:Pioglitazone; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries*; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014110:Touch
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone