Sympathetic Neurotransmitters Decrease Muscle Spindle Afferent Response to Muscle Stretch

Proprioception is the ability to sense body position and motion in space. The primary proprioceptors are the Group Ia and II muscle spindle afferents that innervate the muscle spindle and comprise the sensory arm of the muscle stretch reflex. In‐vivo animal studies have shown that increased sympathetic outflow decreases dynamic and static stretch sensitivity of muscle spindle afferents. However, the direct effect of sympathetic neurotransmitters on muscle spindle afferent stretch sensitivity is not well understood. We hypothesized that the addition of sympathetic neurotransmitters would cause a decrease in responsiveness of muscle spindle afferents via direct action in the muscle spindle. To test this hypothesis, we used an in‐vitro mouse muscle nerve preparation to record muscle spindle afferent firing rates during stretch. The muscle was stretched once every three minutes to 5% resting length for 4 s. Muscle spindle afferent firing rates were determined during the plateau phase of stretch and compared before and after drug addition. Instantaneous firing frequency during a static muscle stretch was measured at different time intervals: beginning of stretch (0.5 seconds into the hold phase or Initial Static Time (IST)) and end of stretch (3.5 seconds into the hold phase or Final Static Time (FST)). All values are expressed as a percentage of the average of 6 pre‐drug baseline responses (BL) and compared to no drug control mice stretched for the equivalent time. Exposure to 100μM norepinephrine (n=6, IST=54.18% BL, FST=37.70% BL) significantly decreased the response to stretch as compared to no drug control animals (n=12, IST=90.82% BL, FST=91.50% BL; p<0.05 One‐way ANOVA w Tukey’s post‐hoc to control). The addition of epinephrine decreased muscle spindle afferent firing, however only significantly at the lower dose of 30μM (n=6, IST=76.90% BL, FST=73.20% BL; p<0.05). The α1 adrenergic receptor agonist, phenylephrine, was used to test the hypothesis that the decrease seen following norepinephrine was due to binding at the α1 adrenergic receptor. No statistically significant decrease was found following phenylephrine administration, however, the sample size used was small (n=3, IST=96.70% BL, FST=96.98% BL). These results show direct effects of sympathetic neurotransmitters on muscle spindle afferent stretch sensitivity and support the hypothesis that sympathetic innervation of the muscle spindle plays an important role in modulating stretch responsiveness. Future studies will use optogenetic techniques to stimulate the sympathetic neurons to determine whether physiologically relevant release of sympathetic neurotransmitters controls muscle spindle afferent sensitivity.Support or Funding InformationThis work was supported by NIH SC3 GM127195 (KAW) and NIH R25 GM071381 (AS and SV).