Mechanical hyperalgesia after spinal nerve ligation in rat is not reversedby intraplantar or systemic administration of adrenergic antagonists

The development of a-adrenergic sensitivity in cutaneous nociceptors has be en postulated as a mechanism for sympathetically maintained pain (SMP), In order to characterize the adrenergic receptors involved, we investigated th e effects of intraplantar administration of alpha(1)-(prazosin) and alpha(2 )-(yohimbine) adrenergic antagonists and systemic injection of phentolamine , a non-specific alpha-adrenergic blocker, on allodynic/hyperalgesic behavi or in an animal model thought to mimic SMP in humans. Peripheral neuropathy in rats was induced by tight ligation of the L5/L6 spinal nerves. Mechanic al hyperalgesia was quantified with von Frey hairs applied either for 3 s o r repetitively to the plantar surface of the hindpaw. Responses to the 3 s duration stimulus were used to determine the paw withdrawal threshold with the up-down paradigm and repetitive stimuli were used to determine the resp onse incidence of paw withdrawal to a given von Frey hair. Mechanical thres holds on the ipsilateral paw decreased significantly after ligation and wer e stable over the following 3 weeks. Intradermal administration of yohimbin e or prazosin did not significantly alleviate mechanical hyperalgesia in L5 /L6 ligated animals. Also systemic administration of phentolamine (1 and 5 mg/kg) did not alleviate the increased incidence of paw withdrawal in L5/L6 spinal nerve ligated animals. These results suggest that an alpha adrenerg ic interaction between sympathetic efferent and somatic afferent fibers doe s not play a critical role for the maintenance of mechanical hyperalgesia i n this model for neuropathic pain. (C) 1999 International Association for t he Study of Pain. Published by Elsevier Science B.V.