Abstract
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.
Highlights
Systemic and local inflammation alter both peripheral and central nervous system function
Eighteen hours post LPS injection, both male and female mice lost a significant amount of weight compared to SAL controls (SAL: 0.03 Æ 0.07 g, n = 73; LPS: À1.98 Æ 0.09 g, n = 74; 2 factor ANOVA, main effect of condition P < 0.001; main effect of sex P = 0.79; sex 9 condition interaction P = 0.93; Table 1)
We found only minor changes in muscle spindle afferent mechanosensation in male mice and no changes in the spinal cord integration of Group Ia afferent sensory information following 18 h of LPS-induced systemic inflammation
Summary
Systemic and local inflammation alter both peripheral and central nervous system function. LPS activates immune and glial cells, causing the release of cytokines and reactive oxygen species, contributing to nociceptor sensitization and maintenance of inflammatory pain (Maier et al 1993; Cunha et al 2005; Binshtok et al 2008; Silva 2010; Ji et al 2016). Inflammation is known to alter central nervous system excitability, contributing to hyperalgesia (Dubner and Ruda 1992; Watkins et al 1995), an increased risk of seizures (Riazi et al 2008), and decreased performance on memory tasks (Arai et al 2001; Chen et al 2008)
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