The efficacy of morphine, pregabalin, gabapentin, and duloxetine on mechanical allodynia is different from that on neuroma pain in the rat neuropathic pain model

Anesth Analg. 2012 Jul;115(1):182-8. doi: 10.1213/ANE.0b013e31824f94ca. Epub 2012 Mar 13.


Background: It has been reported that <50% of neuropathic pain patients are satisfactorily treated with drugs. It is possible that this lack of efficacy of drugs on neuropathic pain might be due to the drugs prescribed, regardless of the origin of pain. We compared the efficacy of orally administered morphine, pregabalin, gabapentin, and duloxetine on mechanical allodynia with that on neuroma pain using the tibial neuroma transposition (TNT) model.

Methods: In the TNT model, the tibial nerve is transected, and the tibial nerve stump is transpositioned to the lateral aspect of the hindlimb. After TNT injury, mechanical allodynia and neuroma pain are observed. Morphine, pregabalin, gabapentin, and duloxetine were administered orally and were examined for the antiallodynic and antineuroma pain effects.

Results: Morphine, pregabalin, gabapentin, and duloxetine attenuated the level of mechanical allodynia in a dose-dependent manner. Morphine-but not pregabalin, gabapentin, and duloxetine-attenuated the neuroma pain. Morphine was less potent in neuroma pain than in mechanical allodynia. In the 2-drug-combination studies (morphine + pregabalin, morphine + duloxetine, and pregabalin + duloxetine), all drug combinations produced a synergistic effect on mechanical allodynia, but not on neuroma pain.

Conclusions: These data indicate that the potency of morphine and the efficacy of pregabalin, gabapentin, and duloxetine on mechanical allodynia are different from those on neuroma pain and that combination therapy is one of different therapeutic choices for the treatment of neuropathic pain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amines / administration & dosage
  • Amines / pharmacology*
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / pharmacology*
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Cyclohexanecarboxylic Acids / administration & dosage
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Duloxetine Hydrochloride
  • Gabapentin
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Neuralgia / physiopathology
  • Neuroma / complications*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pregabalin
  • Rats
  • Rats, Sprague-Dawley
  • Thiophenes / administration & dosage
  • Thiophenes / pharmacology*
  • Time Factors
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / pharmacology


  • Amines
  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Cyclohexanecarboxylic Acids
  • Thiophenes
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Morphine
  • Duloxetine Hydrochloride