Drug
self-administration methods were used to test the hypothesis that rats would self-medicate with a
cannabinoid CB(2) agonist to attenuate a
neuropathic pain state.
Self-medication of the CB(2) agonist (R,S)-AM1241, but not vehicle, attenuated mechanical
hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle
self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241
self-administration did not alter paw withdrawal thresholds in
sham-operated or naive animals. The percentage of active lever responding was similar in naive groups self-administering vehicle or (R,S)-AM1241. The CB(2) antagonist
SR144528 blocked both antiallodynic effects of (R,S)-AM1241
self-medication and the percentage of active lever responding in neuropathic (but not naive) rats. Neuropathic and
sham groups exhibited similar percentages of active lever responding for (R,S)-AM1241 on a fixed ratio 1 (FR1) schedule. However, neuropathic animals worked harder than shams to obtain (R,S)-AM1241 when the schedule of reinforcement was increased (to FR6). (R,S)-AM1241
self-medication on FR1, FR3, or FR6 schedules attenuated nerve injury-induced
mechanical allodynia. (R,S)-AM1241 (900μg intravenously) failed to produce
motor ataxia observed after administration of the mixed CB(1)/CB(2) agonist WIN55,212-2 (0.5mg/kg intravenously). Our results suggest that
cannabinoid CB(2) agonists may be exploited to treat
neuropathic pain with limited
drug abuse liability and central nervous system side effects. These studies validate the use of drug
self-administration methods for identifying nonpsychotropic
analgesics possessing limited abuse potential. These methods offer potential to elucidate novel
analgesics that suppress spontaneous
neuropathic pain that is not measured by traditional assessments of evoked
pain.