Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord

Pain. 2005 Sep;117(1-2):77-87. doi: 10.1016/j.pain.2005.05.035.


In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat peripheral neuropathic pain models the presynaptic inhibitory effect of the mu opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory postsynaptic currents (EPSCs) and miniature EPSCs in superficial dorsal horn neurons is substantially reduced, but only in those spinal cord segments innervated by injured primary afferents. The two nerve injury models also reduce the postsynaptic potassium channel opening action of DAMGO on lamina II spinal cord neurons, but again only in segments receiving injured afferent input. The inhibitory action of DAMGO on ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons is also reduced in affected segments following nerve injury. MOR expression decreases substantially in injured dorsal root ganglion neurons (DRG), while intact neighboring DRGs are unaffected. Decreased activation of MOR on injured primary afferent central terminals and the second order neurons they innervate may minimize any reduction by opioids of the spontaneous pain mediated by ectopic input from axotomized small diameter afferents. Retention of MOR expression and activity in nearby non-injured afferents will enable, however, an opioid-mediated reduction of stimulus-evoked and spontaneous pain carried by intact nociceptor afferents and we find that intrathecal DAMGO (1000 ng) reduces mechanical hypersensitivity in rats with SNL. Axotomy-induced changes in MOR may contribute to opioid- insensitive components of neuropathic pain while the absence of these changes in intact afferents may contribute to the opioid sensitive components.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Blotting, Northern / methods
  • Disease Models, Animal
  • Electric Stimulation / methods
  • Electrophoretic Mobility Shift Assay / methods
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Enzyme Activation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Functional Laterality
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurofilament Proteins / metabolism
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology*
  • Pain Measurement / methods
  • Pain Threshold / physiology
  • Patch-Clamp Techniques / methods
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / metabolism*
  • Peripheral Nervous System Diseases / physiopathology*
  • Physical Stimulation / methods
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism*
  • Spinal Cord* / metabolism
  • Spinal Cord* / pathology
  • Spinal Cord* / physiopathology
  • Synapses / drug effects
  • Synapses / pathology
  • Synapses / physiology*


  • Analgesics, Opioid
  • Neurofilament Proteins
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • neurofilament protein H
  • Extracellular Signal-Regulated MAP Kinases