Rats in which the sciatic nerve is partially transected develop
hyperalgesia which is relieved by
sympathectomy. We carried out experiments using this model of experimental
peripheral neuropathy to examine the peripheral mechanisms underlying sympathetically maintained
pain.
Subcutaneous injection of
noradrenaline (NA) into the affected paw exacerbated the
hyperalgesia but had no effect in control animals. Injection of the non-specific alpha-
adrenergic blocker phentolamine and the alpha 2-adrenergic blocker
yohimbine significantly relieved the
hyperalgesia, while injection of the alpha 1-adrenergic blocker
prazosin had no effect. Peripheral injection of the alpha 2-adrenergic agonist
clonidine had no significant effect, while injection of the alpha 1-adrenergic agonist
phenylephrine produced slight exacerbation of
mechanical hyperalgesia.
Hyperalgesia was eliminated by peripheral injection of
indomethacin into the affected paw. Following a
chemical sympathectomy,
hyperalgesia was eliminated and injection of NA into the hyperalgesic paw had no effect on pain thresholds. We concluded that NA exacerbates
hyperalgesia in this experimental model by acting on alpha 2-adrenoreceptors which are located on post-ganglionic sympathetic terminals. Our results are consistent with the proposal (Levine et al. 1986) that activation of these adrenoreceptors brings about an increased release of
prostaglandins which sensitises nociceptors.