Guanethidine displaces
noradrenaline from sympathetic varicosities, and blocks sympathetic noradrenergic neurotransmission by inhibiting the release of
noradrenaline from depleted neural stores. The aim of this study was to determine whether depletion of
noradrenaline with
guanethidine would oppose
thermal hyperalgesia and/or electrically-evoked
pain in mildly-burnt skin.
Guanethidine was transferred by iontophoresis into a small patch of skin on the forearm of 35 healthy human subjects. The heat-pain threshold to a temperature gradient that increased at 0.5 degrees C/s was then measured at the
guanethidine site, a nearby saline-control iontophoresis site, and in untreated skin. In addition, participants rated
pain intensity to a 47 degrees C stimulus that was applied to each site for 7s. Shortly after the iontophoreses, sensitivity to heat was greater at the
guanethidine site than the two control sites, suggesting that ejection of
noradrenaline from sympathetic varicosities increased sensitivity to heat. One day later, when neural stores of
noradrenaline were depleted, sensitivity to heat did not differ between the
guanethidine and control sites. The
guanethidine pretreatment did not influence
thermal hyperalgesia induced by a mild
burn, but inhibited
pain evoked by electrical stimulation of the skin (0.2 mA direct current for 4 min). These findings indicate that ongoing sympathetic neural discharge does not normally influence
thermal hyperalgesia in inflamed skin, because depleting noradrenergic stores had no effect. However, electrically-evoked release of
noradrenaline may increase nociceptive sensations. Further clarification of this human
pain model could provide insights into the mechanism of
adrenergic hyperalgesia in certain
neuropathic pain syndromes.