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The analgesic properties of [alpha]2-agonists are well known. In experimental models, tumor necrosis factor (TNF)-[alpha] regulates adrenergic responses in the brain. Constitutive TNF-[alpha], in brain regions involved in pain perception, is decreased after the administration of clonidine. We investigated patients undergoing lower-extremity revascularization. Seven patients were treated with clonidine 0.2 mg per os (low), and three patients received 0.4 mg per os clonidine (high) before surgery. Eight patients received placebo and served as controls. Continuous spinal anesthesia was provided by insertion of a pliable catheter into the subarachnoid space. Baseline plasma and cerebrospinal fluid (CSF) samples were obtained before injection of local anesthetic. Samples were analyzed for TNF-[alpha] using a biologic assay. Systemic and central release of catecholamines were assessed by high-pressure liquid chromatography measurement of norepinephrine in plasma and CSF, vanillylmandelic acid and methoxy hydroxyl phenyl glycol in 24-h urinary excretion, respectively. Clonidine 0.2 mg pretreatment decreased TNF-[alpha] concentrations both in plasma and CSF. Patients receiving clonidine had lower pain visual analog scale scores and required less morphine compared with the Placebo group (P < 0.01). Preoperative administration of clonidine decreased catecholamine release in the periphery, as well as in the central nervous system. A smaller norepinephrine concentration in plasma and CSF, and less secretion of vanillylmandelic acid (P < 0.01) and methoxy hydroxyl phenyl glycol in the urine, were observed. Larger dose clonidine (0.4 mg) resulted in no detectable TNF-[alpha] in CSF. These results suggest that an interaction between TNF-[alpha] and the function of adrenergic neurons in the central nervous system may contribute to the sedative and analgesic effects of adrenergic agonists.

(C) 2001 International Anesthesia Research Society