Changes in morphine reward in a model of neuropathic pain

Behav Pharmacol. 2013 Jun;24(3):207-13. doi: 10.1097/FBP.0b013e3283618ac8.


In addition to sensory disturbances, neuropathic pain is associated with an ongoing and persistent negative affective state. This condition may be reflected as altered sensitivity to rewarding stimuli. We examined this hypothesis by testing whether the rewarding properties of morphine are altered in a rat model of neuropathic pain. Neuropathic pain was induced by chronic constriction of the common sciatic nerve. Drug reward was assessed using an unbiased, three-compartment conditioned place preference (CPP) paradigm. The rats underwent two habituation sessions beginning 6 days after surgery. Over the next 8 days, they were injected with drug or vehicle and were confined to one CPP compartment for 30 min. On the following test day, the rats had access to all three compartments for 30 min. Consistent with the literature, systemic administration of morphine dose-dependently increased the CPP in pain-naive animals. In rats with neuropathic pain, however, the dose-dependent effects of morphine were in a bell-shaped curve, with a low dose of morphine (2 mg/kg) producing a greater CPP than a higher dose of morphine (8 mg/kg). In a separate group of animals, acute administration of morphine reversed mechanical allodynia in animals with neuropathic pain at the same doses that produced a CPP. The increased potency of systemic morphine to produce a CPP in animals with neuropathic pain suggests that the motivation for opioid-induced reward is different in the two states.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / therapeutic use*
  • Analysis of Variance
  • Animals
  • Conditioning, Operant / drug effects*
  • Disease Models, Animal
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology
  • Male
  • Morphine / therapeutic use*
  • Neuralgia / drug therapy*
  • Neuralgia / physiopathology
  • Neuralgia / psychology*
  • Pain Threshold / drug effects
  • Rats
  • Rats, Long-Evans
  • Reward*
  • Time Factors


  • Analgesics, Opioid
  • Morphine