Jichu yixue yu linchuang (Sep 2023)
Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ
Abstract
Objective To explore the analgesic effect and underlying mechanisms of dexmedetomidine(DEX) with spared nerve injury(SNI) rat model. Methods Forty-eight SD rats were randomly divided into control group, SNI group, DEX group and DEX+GW9662 group, with 12 rats in each. From first day to 14th days after SNI surgery, rats in DEX group were intra-thecally injected with 2 μg/kg (10 μL) of dexmedetomidine,rats in DEX group were intrathecally injected with 2 μg/kg of dexmedetomidine+300 μg of PPAR-γ inhibitor (GW9662), while rats in control and SNI groups were intrathecally injected with equal volume of solvent. At day 1 before operation, day 3, 7, 14 after operation, paw withdrawal threshold and thermal withdrawal latency were detected to evaluate the painintensity. At post-operative day 14,immunofluorescence staining was used to detect the expression of Iba-1 in spinal dorsal horn, Western blot was used to detect the expression of Iba-1 and PPAR-γ in ipsilateral spinal dorsal horn, ELISA was used to detect the levels of IFN-γ and IL-6 in ipsilateral spinal dorsal horn. Results On postoperative day 7 and 14, compared with control group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn were enhanced in SNI group(P＜0.05). Compared with SNI group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn decreased in EDX group(P＜0.05). Compared with DEX group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal increased in DEX+GW9662 group(P＜0.05). Conclusions Dexmedetomidine obviously inhibits pain sensitization of SNI rats. The underlying analgesic mechanism may be related to the up-regulation of PPAR-γ in spinal dorsal horn.
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