Studies on the central antinociceptive action of cholinomimetic agents

The inhibition of nociceptive reactions by cholinomimetic agents was studied in mice, rats and rabbits using systemic, intraventricular and intracerebral drug application. Tertiary amines (oxotremorine, arecoline and RS 86) as well as a quaternary ammonium compound (carbachol) were used. Various nociceptive reactions showed considerable differences in sensitivity. However, no clear-cut relation to the proposed level of integration of these reactions in the CNS could be found. Carbachol, which hardly passes the blood-brain barrier, was found after systemic administration to be ineffective against nociception but highly effective when injected intraventricularly in rats and rabbits. Oxotremorine too revealed a high antinociceptive activity when injected in this way. This points to a periventricular site of the antinociceptive action of cholinomimetics. Intracerebral microinjection of cholinomimetics into various brain structures of rats was very effective when injection was made into certain diencephalic and mesencephalic areas, but was much less effective when applied to the caudate nucleus. Similarities and differences between the antinociceptive action of cholinomimetics and morphine-like analgesics are discussed in view of the hypothesis that both groups of substances interfere with different links of periventricular nociceptive systems.