Opioid facilitation of rewarding electrical brain stimulation is suppressed in rats with neuropathic pain

Anesthesiology. 2011 Mar;114(3):624-32. doi: 10.1097/ALN.0b013e31820a4edb.


Introduction: Opioids are powerful analgesics, but are also common drugs of abuse. Few studies have examined how neuropathic pain alters the pharmacology of opioids in modulating limbic pathways that underlie abuse liability.

Methods: Rats with or without spinal nerve ligation (SNL) were implanted with electrodes into the left ventral tegmental area and trained to lever press for electrical stimulation. The effects of morphine, heroin, and cocaine on facilitating electrical stimulation of the ventral tegmental area and mechanical allodynia were assessed in SNL and control subjects.

Results: Responding for electrical stimulation of the ventral tegmental area was similar in control and SNL rats. The frequency at which rats emitted 50% of maximal responding was 98.2 ± 5.1 (mean ± SEM) and 93.7 ± 2.8 Hz in control and SNL rats, respectively. Morphine reduced the frequency at which rats emitted 50% of maximal responding in control (maximal shift of 14.8 ± 3.1 Hz), but not SNL (2.3 ± 2.2 Hz) rats. Heroin was less potent in SNL rats, whereas cocaine produced similar shifts in control (42.3 ± 2.0 Hz) and SNL (37.5 ± 4.2 Hz) rats.

Conclusions: Nerve injury suppressed potentiation of electrical stimulation of the ventral tegmental area by opioids, suggesting that the positive reinforcing effects are diminished by chronic pain. Given concerns regarding prescription opioid abuse, developing strategies that assess both analgesia and abuse liability within the context of chronic pain may aid in determining which opioids are most suitable for treating chronic pain when abuse is a concern.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Brain / physiology*
  • Cocaine / pharmacology
  • Dose-Response Relationship, Drug
  • Electric Stimulation*
  • Electrodes, Implanted
  • Heroin / pharmacology
  • Hyperalgesia / physiopathology
  • Hyperalgesia / psychology
  • Ligation
  • Male
  • Morphine / pharmacology
  • Neuralgia / psychology*
  • Pain Measurement / drug effects
  • Pressure
  • Rats
  • Rats, Inbred F344
  • Reward*
  • Self Stimulation
  • Spinal Nerves / injuries
  • Ventral Tegmental Area / physiology


  • Analgesics, Opioid
  • Heroin
  • Morphine
  • Cocaine