Repeated administration of pioglitazone attenuates development of hyperalgesia in a rat model of neuropathic pain.
Recent studies indicate the central neuroimmune and neuroinflammation activation play a critical role in the pathological states of pain. Pioglitazone, a potent synthetic agonists of PPARgamma, has shown to control neuroinflammation in many nervous system-related disorders. The present study was designed to explore the effects of pioglitazone in treating neuropathic pain and its possible neuroimmune mechanisms in the neuropathic pain using lumbar 5 (L5) spinal nerve transection rat model. L5 spinal nerve transection was done to produce hyperalgesia in rats. Pioglitazone (2.5, 5, and 10 mg/kg) was orally administered daily for 14 days, beginning from 1 hour before nerve transection. Mechanical hyperalgesia was measured using Von-Frey filament tests before and after the surgery. Rats were then sacrificed on day 14 postsurgery. The mRNA of inflammatory cytokines such as tumor necrosis factor (TNF-alpha), interleukin (IL-1beta) and nuclear factor kappa B (NF-kappaB) activity in brain were detected using reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay. We found that pioglitazone (5 and 10 mg/kg) can markedly attenuate mechanical hyperalgesia produced by nerve transection, most significantly on the 14th day. The elevated TNF-alpha, IL-1beta, and NF-kappaB in brain were accordingly reduced. Our data could conclude that pioglitazone has ameliorative potential in attenuating the painful state associated with L5 nerve transection, which may further be attributed to inhibiting cerebral proinflammatory cytokines production and NF-kappaB activation in central nervous system.
Jia
Hongbin
H
Department of Anesthesiology, Jinling Hospital, Medicine School of Nanjing University, Nanjing, PR China.
Zhu
Shihai
S
Ji
Qing
Q
Hui
Kangli
K
Duan
Manlin
M
Xu
Jianguo
J
Li
Weiyan
W
D000818:Animals; D001921:Brain / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D000077205:Pioglitazone; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013127:Spinal Nerves / Q000601:surgery; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D053583:Interleukin-1beta; D016328:NF-kappa B; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077205:Pioglitazone