Effects of peripheral antisympathetic treatments in the tail-flick, formalin and autotomy tests

Abstract

The effects of peripheral adrenergic depleting agents on the threshold for non-damaging heat pain (tail-flick test), inflammatory pain associated with tissue injury (formalin test) and chronic pain or dysesthesia associated with nerve lesions (autotomy test) were examined. Tail-flick latencies were increased by agents which deplete peripheral adrenergic transmitters - 6-hydroxydopamine (6-OHDA) and guanethidine - as well as by an agent which prevents the synthesis of noradrenalin [norepinephrine] - FLA63 [bis-(4-methyl-1-homopiperazinylthiocarbonyl)disulfide]. A combination of guanethidine and FLA63 also increased latencies, but no more than either treatment alone. Formalin pain scores were reduced by FLA63 + guanethidine and 6-OHDA, but not by guanethidine or FLA63 alone. The percentage of rats exhibiting autotomy was reduced minimally by 6-OHDA and guanethidine treatments which started the day of surgery, maximally by guanethidine treatments which started 4 days before surgery, and not at all by guanethidine treatments which started 4 days after surgery. The formalin and autotomy tests are interpreted in terms of the possible roles of adrenergic transmitters in stimulating and sensitizing damaged afferents immediately after injury. The tail-flick results, suggest adrenergic transmitters also act in lowering thresholds of normal peripheral receptor-fiber units. The relevance of the findings to the development of chronic pain are discussed.