Peripheral hyperalgesia in experimental neuropathy: mediation by alpha 2-adrenoreceptors on post-ganglionic sympathetic terminals

Pain. 1995 Mar;60(3):317-27. doi: 10.1016/0304-3959(94)00141-z.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Disease Models, Animal
  • Female
  • Hyperalgesia / physiopathology*
  • Nerve Endings / physiology*
  • Norepinephrine / pharmacology
  • Pain Threshold
  • Peripheral Nervous System Diseases / physiopathology*
  • Pilot Projects
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-2 / physiology*
  • Sciatic Nerve / physiology
  • Sympathectomy, Chemical
  • Sympathetic Fibers, Postganglionic / drug effects*


  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-2
  • Norepinephrine