The mode of action of analgesic drugs in adjuvant arthritic rats as an experimental model of chronic inflammatory pain: possible central analgesic action of acidic nonsteroidal antiinflammatory drugs.

The analgesic activities of intracerebroventricular (icv) administrations of some analgesic drugs, morphine, indomethacin, diclofenac, aminopyrine and acetaminophen, were studied in comparison with those of systemic administrations in normal rats and adjuvant arthritic rats. A method for the measurement of analgesic potency in normal rats and adjuvant arthritic rats were developed using the vocalization response as an indicator of pain resulting from electrical stimulation. The systemic and/or icv administered indomethacin and diclofenac produced much more potent analgesic action in adjuvant arthritic rats than in normal rats. Morphine, aminopyrine and acetaminophen given by the two routes showed roughly the same analgesic effect in both types of rats. Simultaneous systemic and icv administrations of indomethacin and/or diclofenac showed an additive effect in normal rats, but showed a synergistic effect rather than a simple additive effect in adjuvant arthritic rats. Those of morphine, aminopyrine and acetaminophen showed only additive effects in both types, except for that of aminopyrine in normal rats. Moreover, the brain and serum levels of non-metabolized indomethacin and aminopyrine were measured after the normal and adjuvant arthritic rats were systemically given these drugs. In adjuvant arthritic rats, the icv effective dose of indomethacin was the same as the brain level of non-metabolized indomethacin after the systemic administration. The effective dose of indomethacin administered icv in the normal rats was 17 times higher than the brain level of non-metabolized indomethacin administered systemically. The icv effective dose of aminopyrine was 4-4.5 times higher than the level of the brain concentration of non-metabolized drug in both types of rats.(ABSTRACT TRUNCATED AT 250 WORDS)