Supersensitivity to Ach in Muscles After Prolonged Nerve Block

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Abstract
The sensitivity of skeletal muscle membrane to cholinergic drugs is normally restricted to the end-plate region. Following the interruption of the motor nerve, extra-junctional regions of the muscle fibres become sensitive to ACh (Axelsson & Thesleff, 1959). Factors which may contribute to the spread of the ACh sensitivity are (I) interruption of transport down the motor axons and toward the muscle of some substances which inhibit the supersensitivity; (II) interruption of the spontaneous release of ACh from the nerve terminals; (III) prolonged electrical and mechanical inactivity in the muscle fibres. For each of these factors there are investigators who regard it as the predominant one (see references in L0MO & Rosenthal, 1972, and in Robert & Oester, 1970, b). One of the experimental approaches designed to test possibility (III) was to inhibit electrical activity, while sparing anatomical integrity, in motor nerves for periods of time equal to those required for the ACh supersensitivity to develop following denervation. The technique used by the two groups of workers mentioned was to place anaesthetic-impregnated silicone cuffs around the muscle nerves for periods of up to 14 days. The results of Robert & Oester (1970, a) suggested that absence of activity in nerves and muscles did not cause ACh sensitivity to develop, whereas the more recent results of L0MO & Rosenthal (1972) indicated the opposite. The two sets of results could not really be compared because rabbits were used by the first group and rats by the second, and lidocaine base was used by the first, and mainly marcaine hydrochloride by the second mentioned authors. The possibility existed therefore that the inconsistent results were due either to a specificity in the responsiveness to nerve anaesthesia in the two species of rodents or to a specificity of action of the local anaesthetics contained in the nerve cuffs. Another possibility was that the contradictory conclusions were reached because of differences in the methods used to appraise the effectiveness of the anaesthetic action and of the ACh sensitivity of the muscles. It was decided therefore to repeat the experiments in such a way that the mentioned factors would be excluded.