Neuromuscular Pharmacology: Drugs and Muscle Spindles

Abstract

This review is limited to a consideration of the direct and indirect actions of drugs on muscle spindle function. A detailed description of the various sensory endings, their characteristic responses to stimuli, and the function of these receptors in reflexes is outside the scope of this review. These topics have been discussed in a recent symposium (8) and other reviews (34,47,64,76,95).The mammalian muscle spindles are of particular interest since they contain the afferent ending for one of the basic reflexes, the stretch reflex. In addition to a complicated afferent system of one or more stretch sensitive endings, they possess specialized intrafusal muscle fibers which function as regulators of the sensitivity of the afferent receptor endings. The assess ment of drug effects upon these intrafusal fibers has, by necessity, been limited to indirect methods. Stimulation of the small, high threshold myeli nated fusimotor4 nerves innervating the intrafusal muscle fibers results in an increase in the frequency of discharge of spindle afferent nerves as well as an increase in the sensitivity to stretch of the sensory ending with, however, no alteration in gross muscle tension.It has not been proven that intrafusal neuromuscular (n-m) transmission is cholinergic but all data obtained to date are consistent with this assump tion. The endplates contain cholinesterase (30,31,32,75,89), transmission is blocked by extrafusal anticholinergic blocking agents (table I), and anti cholinesterases facilitate transmission (90) and antagonize tubocurarine block (54,55,80).Agents acting directly on spindles.-Tubocurarine, its dimethyl ether, and gallamine have been reported to block intrafusal n-m transmission ( Table 1). The intrafusal fibers appear to be less sensitive than the extrafusal; however, the difference in sensitivity is not great and it is difficult to block all extrafusal fibers and leave intrafusal n-m transmission unaffected (54, 55). Succinylcholine (SCh) rather selectively blocks extrafusal n-m trans-1 The survey of the literature pertaining to this review was concluded May 1962. S Abbreviations used in this chapter include: ACh (acetylcholine); nom (nerve muscle, neuro-muscular); SCh (succinylcholine).

Monitoring of head injury by myotatic reflex evaluation

“…In practice, central effects seem unlikely, as these agents tend not to cross the blood-brain barrier in significant quantities 13. However, non-depolarising blockade is known to extend to the intrafusal fibres of muscle spindles14; by unloading spindle receptors, this might theoretically reduce their sensitivity. For the reasons discussed above, a universal reduction in sensitivity to percussion would not affect TI 80 , but reduced sensitivity to vibration would reduce TI 80 .…”

Characteristics of knee joint receptors in the cat

“…They were slowly adapting and responded to joint movement, but in contrast to typical joint receptors all responded to succinylcholine chloride (0 1-0 2 mg i.v.). This drug excites muscle spindle afferent fibres (Smith, 1963). To test the possibility that spindle-like afferents might regularly be found in the posterior articular nerve, gross recordings were made from the nerve before and after administration of succinylcholine.…”

Rat Isolated Phrenic Nerve‐diaphragm Preparation for Pharmacological Study of Muscle Spindle Afferent Activity: Effect of Oxotremorine

“…There -has' been a considerable number of investigations on the influence of drugs on fusimotor functions and spindle afferent activity (for references, see Smith, 1963;Paintal, 1964;Matthews, 1964;1972). However, as far as mammalian muscle spindles are concerned the assessment of pharmacological experiments is hampered by the lack of a suitable isolated preparation which would allow an unequivocal differentiation between direct and systemic drug effects.…”