Supersensitivity to
noradrenaline contributes to certain vascular disorders (e.g.,
hypertension) and chronic
neuropathic pain conditions (e.g.,
complex regional pain syndrome). We aimed to develop a procedure for inducing
adrenergic supersensitivity that could be used to investigate the role of
catecholamines in these clinical conditions. In the first study, three doses of
guanethidine were administered by iontophoresis to separate small patches of skin in the forearm of healthy human volunteers. Four to five hours later. the
vasoconstrictor response to the
adrenergic releasing agent
tyramine was inhibited in a dose-dependent manner by iontophoretic pretreatment with
guanethidine, indicating that
guanethidine had depleted endogenous
adrenergic stores. In a second study,
guanethidine and saline were administered by iontophoresis four times over approximately 2 weeks at separate sites in the forearm. One to two days after the final pretreatment, vasoconstriction to the iontophoresis of a weak dose of
noradrenaline was enhanced at sites pretreated with
guanethidine. To investigate the effect of
guanethidine pretreatment on
thermal hyperalgesia. the experimental sites were sensitized to heat by the topical application of 0.6%
capsaicin. Both before and after the application of
capsaicin, the heat-pain threshold and heat-
pain ratings to suprathreshold stimulation were similar at sites pretreated for 2 weeks with
guanethidine or saline. However, after the iontophoresis of
noradrenaline,
thermal hyperalgesia was greater at the
guanethidine-pretreated site than the saline pretreated site. These observations indicate that prolonged depletion of
adrenergic stores by
guanethidine induces
adrenergic supersensitivity in cutaneous vessels, and that
adrenergic supersensitivity enhances
thermal hyperalgesia in the presence of
noradrenaline.