Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline in a rat model of neuropathic pain

In the present study, we sought to determine whether administration of caff eine, a non-selective adenosine receptor antagonist, would affect the therm al antihyperalgesic efficacy of acute amitriptyline in a rat model of neuro pathic pain. Rats were rendered neuropathic by unilateral tight ligation of the fifth and sixth lumbar spinal nerves, and tested for thermal hyperalge sia using a focused beam of light. Systemic administration of caffeine (1.5 -7.5 mg/kg), at the same time as amitriptyline, blocked the thermal antihyp eralgesic effect of 10 mg/kg amitriptyline. The greatest degree of block ex erted by caffeine was observed with 3.75 mg/kg (100% block), a dose that ha d no observable intrinsic effect. Spinal administration of amitriptyline (6 0 mu g) exhibited a mild antihyperalgesic effect that was unaffected by pre treatment with intrathecal caffeine (100 mu g). Peripheral administration o f amitriptyline into the neuropathic paw (under brief anesthesia) produced an antihyperalgesic effect at both 30 and 100 nmol, with a greater effect b eing observed at 100 nmol. Coadministration of caffeine (1500 nmol) partial ly antagonized the effects of both doses of amitriptyline. The results of t his study suggest that the thermal antihyperalgesic effect of acute amitrip tyline in this model may involve enhancement of an endogenous adenosine ton e. This involvement is important in light of the widespread consumption of caffeine, which may potentially act to reduce the benefits of amitriptyline in the treatment of neuropathic pain. (C) 2000 Elsevier Science B.V. All r ights reserved.