[Alpha 2-adrenergic agonists. Use in chronic pain--a meta-analysis]

alpha(2)-adrenergic agonists, mimicking the action of the inhibitory transmitter norepinephrine, cause antinociception due to postsynaptic inhibition of spinothalamic projection neurons, presynaptic inhibition at the central nervous system termination of primary sensory nerves, presynaptic inhibition of brainstem noradrenergic neurons and a generalized decrease in central nervous system sympathetic efferent activity. There is a mutual potentiation of antinociceptive effects of clonidine and morphine. Clonidine is used in chronic pain states for treatment of neuropathic, neuralgic and deafferentiating pain. Based on a meta-analysis of the studies published in the years 1996-1996, the therapeutic efficacy of systematically administered clonidine was evaluated in chronic pain states. Out of 403 screened published studies, only 9 fulfilled the selection criteria. Besides three case reports with successful clonidine treatment, four placebo-controlled studies could be analyzed treating the following chronic pain states: chest pain despite normal coronary angiograms; painful diabetic neuropathy; postherpetic neuralgia; hyperalgia in patients with sympathetically maintained pain and chronic low back pain. Although three studies demonstrated statistically significant improvement in pain scores, the improvement in pain relief in these cases was slight. Long-term treatment was successful in a few responders over a period of 17 months. Hyperalgesia caused by sympathetically maintained pain was relieved by topical (transdermal) application of clonidine. Based on this evaluation a grade C recommendation is derived, which relates to responders. Successful treatment is expected only in pain states with increased sympathetic nervous system activity. Therefore, in chronic pain, treatment with systemic clonidine is of no significant value.