Loss of spinal mu-opioid receptor is associated with mechanical allodynia in a rat model of peripheral neuropathy

Pain. 2006 Jul;123(1-2):117-26. doi: 10.1016/j.pain.2006.02.017. Epub 2006 Mar 27.

Abstract

The present study investigated whether the loss of spinal mu-opioid receptors following peripheral nerve injury is related to mechanical allodynia. We compared the quantity of spinal mu-opioid receptor and the effect of its antagonists, such as naloxone and CTOP, on pain behaviors in two groups of rats that showed extremely different severity of mechanical allodynia 2 weeks following partial injury of tail-innervating nerves. One group (allodynic group) exhibited robust signs of mechanical allodynia after the nerve injury, whereas the other group (non-allodynic group) showed little allodynia despite having suffered the same nerve injury. In addition, we investigated the quantity of spinal mu-opioid receptor and the effect of its antagonists on pain behaviors after the rats had recovered from mechanical allodynia 16 weeks following nerve injury. Immunohistochemical and Western blot analyses at 2 weeks after nerve injury indicated that spinal mu-opioid receptor content was more reduced in the allodynic group compared to the non-allodynic group. Intraperitoneal naloxone (2 mg/kg, i.p.) and intrathecal CTOP (10 microg/rat, i.t.) administration dramatically induced mechanical allodynia in the non-allodynic group. However, as in naïve animals, neither the loss of spinal mu-opioid receptors nor antagonist-induced mechanical allodynia was observed in the rats that had recovered from mechanical allodynia. These results suggest that the loss of spinal mu-opioid receptors following peripheral nerve injury is related to mechanical allodynia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axotomy
  • Disease Models, Animal
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Injections, Intraperitoneal
  • Injections, Spinal
  • Male
  • Molecular Sequence Data
  • Naloxone / administration & dosage
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Neuralgia / etiology
  • Neuralgia / physiopathology*
  • Posterior Horn Cells / physiopathology
  • Pressure / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / physiology*
  • Somatostatin / administration & dosage
  • Somatostatin / analogs & derivatives
  • Somatostatin / pharmacology
  • Spinal Cord / physiopathology*
  • Spinal Nerves / injuries
  • Spinal Nerves / physiopathology*
  • Stress, Mechanical
  • Tail / innervation

Substances

  • Narcotic Antagonists
  • Oprm1 protein, rat
  • Receptors, Opioid, mu
  • phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
  • Naloxone
  • Somatostatin