The central nucleus of the amygdala contributes to the production of morphine antinociception in the formalin test

Pain. 1995 Nov;63(2):141-152. doi: 10.1016/0304-3959(95)00027-P.


The rat paw formalin test is a model of prolonged pain due to mild tissue injury. There is some evidence suggesting that morphine does not produce antinociception in the formalin test via the brain-stem and spinal cord circuitry normally associated with antinociception. Furthermore, morphine appears to require an intact forebrain in order to function as an analgesic for formalin pain. In the 2 experiments reported here, we investigated the possibility that the central nucleus of the amygdala (Ce) contributes to the production of morphine antinociception (MA) in the formalin test. Nociception in this test occurs in 2 phases, with the 1st phase occurring 0-5 min after formalin injection and the 2nd phase beginning 10-15 min after injection and continuing for approximately 1 h. In Exp. 1, bilateral neurotoxic lesions of the Ce, but not lesions of the adjacent basolateral nucleus (BL), reliably attenuated MA (7 mg/kg morphine sulfate) during the 2nd phase of the formalin test without affecting baseline nociception. These results were obtained regardless of whether the rating scale method or flinch-frequency method of nociceptive scoring was used. During the 1st phase, Ce lesions reliably attenuated MA as measured by the flinch-frequency method, but not as measured by the rating scale method. In Exp. 2, Ce lesions also reliably attenuated the antinociception produced by 12 mg/kg morphine sulfate during the 2nd phase of the formalin test. Antinociception appeared to be almost completely re-instated, however, if the dose of morphine was raised to 20 mg/kg. The results indicate that neurons originating from the Ce contribute to the production of MA during the 2nd phase, and possibly the 1st phase, of the formalin test, especially at relatively lower doses of morphine. This suggests that in addition to coordinating conditioned antinociceptive responses, the amygdala may be a component of endogenous antinociceptive circuitry. These and other issues are discussed with reference to the spino-ponto-amygdaloid nociceptive pathway, and the proposed role of the amygdala in the mediation of defense reactions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amygdala / drug effects
  • Amygdala / pathology
  • Amygdala / physiology*
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Brain Mapping
  • Formaldehyde / pharmacology*
  • Hindlimb
  • Injections
  • Male
  • Morphine / pharmacology*
  • N-Methylaspartate / pharmacology
  • Nociceptors / drug effects*
  • Pain Measurement
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Analgesics, Opioid
  • Formaldehyde
  • N-Methylaspartate
  • Morphine