α1-Adrenoceptors augment thermal hyperalgesia in mildly burnt skin

The effect of the α1-adrenoceptor agonist phenylephrine on sensitivity to heat was investigated at three sites of mild burn injury in the cutaneous forearm of 19 healthy participants. Two of the sites were pre-treated with the α1-antagonist terazosin, to determine whether the effect of phenylephrine was mediated by α1-adrenoceptors. Terazosin was administered before the burn injury at one site, and after the burn injury at the other site. In another 15 participants, the nociceptive effect of the α2-adrenoceptor agonist clonidine was investigated with and without prior treatment with the α2-antagonist rauwolscine. Drugs were introduced into the skin by iontophoresis, and burns were induced by heating the skin to 48 °C for 2 min. Heat pain thresholds to a temperature ramp (0.5 °C/s), and heat pain ratings to a thermal stimulus (45 °C, 7 s), were determined before and after the administration of each drug. Thermal hyperalgesia provoked by phenylephrine was inhibited by terazosin administered after the burn injury, but not by terazosin administered before the burn injury. However, neither α2-adrenoceptor stimulation nor blockade affected sensitivity to heat in the mildly burnt skin. These findings suggest that stimulation of cutaneous α1-adrenoceptors increased the excitability of heat-sensitized nociceptive afferents. As terazosin was more effective when administered in burnt skin, an inflammatory response induced by the burn injury may have facilitated access of adrenergic agents to α1-adrenoceptors.