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

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 dysaesthesia 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 noradrenaline--FLA63. 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 that exhibited 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 results obtained in 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, however, suggest that adrenergic transmitters also act in lowering thresholds of normal peripheral receptor-fibre units. The relevance of the findings to the development of chronic pain are discussed.