Effects of clonidine on bilateral pain behaviors and inflammatory response in rats under the state of neuropathic pain.
This study was conducted to investigate the effects of clonidine on bilateral pain behaviors and inflammatory responses in neuropathic pain induced by partial sciatic nerve ligation (PSNL), and to better understand whether the antinociception of clonidine was related to α(2)-adrenoceptor mechanisms. Rats were divided randomly into five groups: sham-operation with saline, i.p.; PSNL with clonidine (0.2mg/kg) or saline, i.p.; PSNL with yohimbine (2mg/kg) followed by clonidine (0.2mg/kg), i.p.; and PSNL with naloxone (0.3mg/kg) followed by clonidine (0.2mg/kg), i.p. On post-operative days 1, 3, 7, 14, and 21, both ipsilateral and contralateral pain behaviors were measured. In rats receiving antagonists, bilateral behavioral changes were measured on day 14. Bilateral paw pressure threshold and paw withdrawal latencies were measured, and the extent of glial activation was dertermined by measuring macrophage antigen complex-1 (Mac-1) and glial fibrillary acidic protein (GFAP). Additionally, the levels of tumor necrosis factor α (TNF-α) and interleukin (IL)-6 were determined. PSNL induced bilateral behavioral hyperalgesia, with the ipsilateral level displaying a higher extent of behavior changes than the contralateral side. In addition, the glial activation markers and cytokine production were augmented bilaterally. Clonidine caused significant attenuation of bilateral mechanical allodynia and thermal hyperalgesia, accompanied by inhibition of glial activation and the expression of cytokines. The effects of clonidine were blocked by the α(2)-adrenoceptor antagonist yohimbine and partially reversed by the μ-opioid receptor antagonist naloxone. These data suggest that the bilateral antinoceptive effects of clonidine might mediate through immunomodulation by acting on α(2)-adrenoceptor in rats undergoing neuropathic pain.