Lipopolysaccharide-induced inflammation does not alter muscle spindle afferent mechanosensation or sensory integration in the spinal cord of adult mice.

Inflammation is known to alter nervous system function, but its effect on muscle spindle afferent mechanosensation and sensory integration in the spinal cord has not been well studied. We tested the hypothesis that systemic inflammation induced by an intraperitoneal injection of the endotoxin lipopolysaccharide (LPS; 7.5 × 105 endotoxin units/kg 18 h before experiment) would alter muscle spindle afferent mechanosensation and spinal cord excitability to Group Ia input in male and female adult C57Bl/6 mice. LPS injection caused a systemic immune response, evidenced by decreased white blood cell, monocyte, and lymphocyte concentrations in the blood, increased blood granulocyte concentration, and body weight loss. The immune response in both sexes was qualitatively similar. We used an in vitro muscle-nerve preparation to assay muscle spindle afferent response to stretch and vibration. LPS injection did not significantly change the response to stretch or vibration, with the exception of small decreases in the ability to entrain to high-frequency vibration in male mice. Similarly, LPS injection did not alter spinal cord excitability to Group Ia muscle spindle afferent input as measured by the Hoffman's reflex test in anesthetized mice (100 mg/kg ketamine, 10 mg/kg xylazine). Specifically, there were no changes in M or H wave latencies nor in the percentage of motor neurons excited by electrical afferent stimulation (Hmax /Mmax ). Overall, we found no major alterations in muscle proprioceptor function or sensory integration following exposure to LPS at a dose and time course that causes changes in nociceptor function and central processing.

Piezo2 is the principal mechanotransduction channel for proprioception.

Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons showed severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of parvalbumin-expressing neurons that predominantly mark proprioceptors was dependent on Piezo2 expression in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings was markedly reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors.