Effect of naloxone on primary and secondary hyperalgesia induced by the human burn injury model

Opioid antagonists may change the responses in models of experimental hyperalgesia. This indicates a possible involvement of the endogenous opioid system in these models. The aim of the present study was to evaluate whether activation of the endogenous opioid system could be demonstrated in the human burn injury model of cutaneous hyperalgesia, using an intravenous challenge with the non-selective opioid antagonist naloxone.

We studied 25 healthy male volunteers aged 20-31 yrs in a randomised, double-blind, triple crossover design. A 25x50 mm rectangular burn injury was produced on the calf on 3 separate days, at least 1 week apart. Subjects received an intravenous bolus dose of naloxone 0.4 mg, 10 mg or placebo 3 h after induction of the burn injury.

Primary and secondary hyperalgesia was induced by the burn injury. Naloxone did not affect any of the measured variables: heat pain detection threshold in non-injured or injured tissue, pain produced by short or prolonged noxious heat in non-injured or injured tissue, secondary hyperalgesia elicited by pin prick or stroke, or pain produced by short or prolonged noxious mechanical stimulation in non-injured tissue. No significant adverse effects of naloxone were encountered.

Activation of an endogenous opioid response following induction of hyperalgesia in human volunteers by a burn injury could not be demonstrated with an intravenous naloxone challenge. These findings suggest that the endogenous opioid response is not a confounding factor in this model.