Clonidine suppresses plasma and cerebrospinal fluid concentrations of TNF-alpha during the perioperative period

The analgesic properties of alpha (2)-agonists are well known. In experimen tal models, tumor necrosis factor (TNF)-alpha regulates adrenergic response s in the brain. Constitutive TNF-alpha, in brain regions involved in pain p erception, is decreased after the administration of clonidine. We investiga ted patients undergoing lower-extremity revascularization. Seven patients w ere 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 pla cebo and served as controls. Continuous spinal anesthesia was provided by i nsertion of a pliable catheter into the subarachnoid space. Baseline plasma and cerebrospinal fluid (CSF) samples were obtained before injection of lo cal anesthetic. Samples were analyzed for TNF-alpha using a biologic assay. Systemic and central release of catecholamines were assessed by high-press ure liquid chromatography measurement of norepinephrine in plasma and CSF, vanillylmandelic acid and methoxy hydroxyl phenyl glycol in 24-h urinary ex cretion, respectively. Clonidine 0.2 mg pretreatment decreased TNF-alpha co ncentrations both in plasma and CSF. Patients receiving clonidine had lower pain visual analog scale scores and required less morphine compared with t he Placebo group P < 0.01). Preoperative administration of clonidine decrea sed catecholamine release in the periphery, as well as in the central nervo us system. A smaller norepinephrine concentration in plasma and CSF, and le ss secretion of vanillylmandelic acid (P < 0.01) and methoxy hydroxyl pheny l glycol in the urine, were observed. Larger dose clonidine (0.4 mg) result ed in no detectable TNF-alpha in CSF. These results suggest that an interac tion between TNF-alpha and the function of adrenergic neurons in the centra l nervous system may contribute to the sedative and analgesic effects of ad renergic agonists.