SUMMARY1. Presynaptic inhibition of muscle spindle I a afferents by afferents from the same and other muscles has been studied in the human lower limb. The experiments have utilized conditioning of test monosynaptic reflexes by vibration of both the test and other muscles.2. The pattern of inhibition invariably includes autogenetic actions.3. There are powerful effects from flexor to extensor Ia afferents. Actions from flexor to flexor, and from extensor to extensor, are weaker. Actions from extensors to flexors are very weak.4. The strength of presynaptic inhibition from one muscle type to another weakens as the muscles considered become more anatomically distant.5. The inhibition studied both by vibration and by electrical conditioning stimulation of nerves becomes weaker during voluntary isometric contraction of the test muscle. It is strongest at rest and during antagonist contraction.6. Evidence is provided suggesting that descending control is the primary cause of this modulation of inhibition during contraction.7. Stimulation of afferents in cutaneous nerves reduces group I presynaptic inhibition of I a afferents.

SUMMARYTransmission in a pathway mediating presynaptic inhibition of soleus I a afferent terminals was assessed from the reduction of soleus muscle H reflex amplitude brought about by a short conditioning vibration pulse applied to the anterior tibialis muscle. In a group of young subjects (aged between 21 and 37 years) the mean reduction in reflex size with the limb relaxed was to 29-2 % of control, whereas in a group of older subjects (aged between 59 and 74 years) the reduction was significantly less, to 55 0% of control (P < 0 001, Student's t test). In the younger group the amount of presynaptic inhibition elicited was inversely related to the plantar-flexor torque produced by tonic contraction of gastrocnemius-soleus; often at higher torques no reduction in reflex size was seen. In contrast the older group showed only a slight reduction in presynaptic inhibition with increasing torque, so that at torques of 5 and 7 Nm the amount of presynaptic inhibition elicited was similar in the younger and older groups. The older subjects were not able to sustain the higher torques produced by the younger subjects. These results suggest that the control of transmission in this spinal pathway changes with increasing age.

In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrogoniometer was used to assess muscle tone at knee extensors, applying Wartenberg Further statistical analysis showed a strong within patient linear correlation between plasma concentrations and antispastic action at 4 and 8 mg doses (p = 0-014 and 0'004 respectively), but only weak between patient correlations. The analysis of the dose-plasma concentration relation showed results consistent with linear pharmacokinetics. The comparison of changes in the R2 ratio with concomitant Ashworth scores showed a significant correlation between the two. It is concluded that there are linear correlations between single doses, plasma concentrations, and antispastic action of tizanidine. Because of the strong within patient but weak between patient correlation between plasma concentrations and antispastic action of tizanidine the effective doses should be determined individually. (9 Neurol Neurosurg Psychiatry 1994;57: 1355-1359 Tizanidine (SirdaludO) is a centrally active a, adrenergic receptor agonist with potent myotonolytic action.l The substance was shown to suppress selectively polysynaptic spinal reflexes while sparing the monosynaptic reflexes.5 Clinical investigations have consistently shown an antispastic effect of tizanidine that was associated with little undue muscle weakness,69 sometimes associated with an improvement in paresis.10 There is, however, little information on the correlation between the antispastic effect and plasma concentrations of tizanidine. ' We report data on the correlations between single doses, plasma concentrations, and antispastic action of tizanidine in patients with spasticity due to multiple sclerosis, by means of an objective quantitative method and a clinical scale for the assessment of spasticity. Methods PATIENT SELECTIONSeventeen patients were entered into the study, but one patient was excluded from further analysis because the baseline severity of spasticity decreased during the study to below that stipulated in the protocol. There were 13 women and four men, mean age 43 (range 24-58) years. All patients had definite multiple sclerosis, diagnosed by clinical criteria and paraclinical investigations. Spasticity had been present for a mean of 70 (range 12-180) months and had been stable for a mean of 17 (range 2-48) months. Extensor spasticity reaching a minimum score of 2 on the Ashworth scale in at least one leg and remaining stable for at least one month was required as an entry criterion. All patients had a baseline score of either 2 or 3 on knee extensors, none had a score of 4, and none of them were bedridden. Patients receiving any drugs with antispastic action, those with significant systemic diseases, local complications, an exacerbation of the disease, or abnormalities in laboratory tests ...

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SUMMARY1. Autogenetic inhibition from contraction receptors was measured by eliciting contractions of the soleus muscle in the decerebrate cat. Inhibitory feedback was detected when the tension increment f, produced by stimulating motor fibres in the presence of a background reflex contraction, was smaller than the tension d elicited by the same stimulus in the absence of reflex action. Tendon vibration was applied throughout to clamp primary spindle afferents at a constant firing rate, thereby preventing spindle unloading from disfacilitating the reflex contraction.2. The reduction in tension d-f varied roughly linearly with the size of the tension stimulus f. Feedback gain was proportional to d-f/f, i.e. the ratio of inhibited tension to stimulus tension. It was computed by averaging over several measurements obtained with stimuli of different sizes, and ranged between 0 and 0-88 in ten animals. The average gain, 0 39, implies that voluntary muscle force is reduced by approximately 27 % through the direct inhibition of a-motoneurones from homonymous contraction receptors.3. Inhibitory feedback gain did not appear to co-vary with the background reflex contraction. When measured without vibration, however, a positive covariance did emerge, suggesting that this is due to unloading of muscle spindles, either by extrafusal muscle shortening or by inhibition of fusimotor neurones.4. Inhibited tension varied linearly with the estimated increment in Ib afferent firing. On the assumption that group I b afferents carried the entire inhibitory signal, inhibitory feedback gain measured with vibration was used to predict the size of the gain if vibration had not been applied. Feedback gain calculated in this way was reduced by still did not vary with reflex tension.5. In one animal with signs of brain stem trauma, feedback gain was increased to around six. It is argued that inhibitory feedback in the intact animal can rise to comparable values, as a result both of convergence of signals from different muscles and of supraspinal facilitation.