Noradrenaline hyperalgesia is mediated through interaction with sympathetic postgahglionic neurone terminals rather than activation of primary afferent nociceptors

Abstract

In hyperalgesic states, observed commonly as a major symptom of tissue inflammation or after central or peripheral nerve injury, non-noxious stimuli produce pain and noxious stimuli are perceived as more painful than usual. The mechanisms underlying the generation of hyperalgesia are not known. In patients with causalgia (burning pain and severe hyperalgesia after a nerve injury) activation of sympathetic post-ganglionic neurones or application of noradrenaline to painful skin exacerbates pain and hyperalgesia¹ while sympathectomy may afford complete relief². One suggestion is that noradrenaline released from sympathetic post-ganglionic neurones increases the discharge of damaged small-diameter afferents^3,4 by a direct action on the primary afferents^5,6. Here we present a new model for noradrenaline-sensitive hyperalgesia and demonstrate that the site of action of noradrenaline is not on the primary afferents but rather is presynaptic on the sympathetic post-ganglionic terminals.