Effects of Cholinergic and Dopaminergic Agents on Pain and Morphine Analgesia Measured by Three Pain Tests

Exp Neurol. 1983 Jul;81(1):167-76. doi: 10.1016/0014-4886(83)90166-8.


The effects of several cholinergic and dopaminergic agents on pain and morphine analgesia were assessed using three pain tests. These tests--tail-flick, hot-plate, and Formalin--allow comparison of the effects of different noxious stimuli and different motor responses. Each pain test yielded a unique constellation of cholinergic and dopaminergic influences, suggesting that variation of stimulus and response parameters can change the functional expression of cholinergic and dopaminergic systems related to pain processing. Significant analgesia was observed in the Formalin test, compared with the saline control, after administration of choline (30 or 60 mg/kg), atropine (2 mg/kg), mecamylamine (2 mg/kg or 10 mg/kg), or apomorphine (0.3 or 8 mg/kg). No analgesic effects in this test were observed after atropine (10 mg/kg) or pimozide (0.125 or 0.5 mg/kg). In contrast, there was no evidence of analgesia produced by any of these drugs, in the doses given, in the hot-plate test, and only apomorphine (8 mg/kg) produced analgesia in the tail-flick test. When these cholinergic and dopaminergic agents were administered to rats after an injection of 2.5 mg/kg morphine, which by itself has been shown not to produce analgesia in any of the tests, a general pattern of facilitation was observed in the Formalin test but not in the tail-flick or hot-plate tests. Facilitation was produced by choline, atropine, mecamylamine, apomorphine, and pimozide (at 0.5 mg/kg but not 0.125 mg/kg). The data suggest that differences in the type of noxious stimulation and in the motor responses required in various pain tests are crucial in determining the observed pharmacologic profile of pain and opiate analgesia.

Publication types

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

MeSH terms

  • Animals
  • Drug Synergism
  • Formaldehyde / pharmacology
  • Male
  • Morphine / metabolism
  • Morphine / therapeutic use*
  • Pain / drug therapy*
  • Pain / metabolism
  • Parasympathomimetics / pharmacology*
  • Rats
  • Rats, Inbred Strains


  • Parasympathomimetics
  • Formaldehyde
  • Morphine