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

Pain. 1999 Feb;79(2-3):135-41. doi: 10.1016/s0304-3959(98)00185-7.


The development of alpha-adrenergic sensitivity in cutaneous nociceptors has been postulated as a mechanism for sympathetically maintained pain (SMP). In order to characterize the adrenergic receptors involved, we investigated the effects of intraplantar administration of alpha1-(prazosin) and alpha2-(yohimbine) adrenergic antagonists and systemic injection of phentolamine, a non-specific alpha-adrenergic blocker, on allodynic/hyperalgesic behavior 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. Mechanical hyperalgesia was quantified with von Frey hairs applied either for 3 s or 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 response incidence of paw withdrawal to a given von Frey hair. Mechanical thresholds on the ipsilateral paw decreased significantly after ligation and were stable over the following 3 weeks. Intradermal administration of yohimbine 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 adrenergic interaction between sympathetic efferent and somatic afferent fibers does not play a critical role for the maintenance of mechanical hyperalgesia in this model for neuropathic pain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists / administration & dosage
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / physiopathology*
  • Injections, Intradermal
  • Ligation
  • Male
  • Pain Measurement / drug effects
  • Phentolamine / administration & dosage
  • Phentolamine / pharmacology
  • Prazosin / administration & dosage
  • Prazosin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Nerves / drug effects
  • Spinal Nerves / physiopathology
  • Yohimbine / administration & dosage
  • Yohimbine / pharmacology


  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Yohimbine
  • Prazosin
  • Phentolamine