Lipopolysaccharide‐Induced Inflammation does not Alter Spinal Cord Excitability in Female or Male mice

Abstract

Peripheral inflammation can alter the excitability of dorsal horn interneurons and increase flexor reflex strength (Dubner & Ruda, 1992), but the effect of peripheral inflammation on the stretch reflex is not as well understood. Our lab has preliminary evidence that 18 hrs of systemic inflammation induced with lipopolysaccharide (LPS; a bacterial coat protein) causes a blunted response to muscle vibration in mouse muscle spindle afferents, the sensory neurons in the stretch reflex. This would suggest that muscle stretch reflex strength following LPS would be decreased if there were no changes in spinal cord excitability. To test the hypothesis that LPS induced systemic inflammation alters spinal cord excitability, we measured the H reflex, or electrical analog of the stretch reflex, in mice receiving an injection of LPS (0.5 mg/kg) or saline (200 μl) 18 hrs before experimentation. Mice were anesthetized with an intraperitoneal injection of ketamine (100mg/kg) and xylazine (10mg/kg). The sciatic nerve was exposed and stimulated with bipolar tungsten electrodes at current strengths from H wave threshold (T) to 8T (20 × 0.1 ms pulses at 0.1Hz). Bipolar recording electrodes were placed in the 4th dorsal interossei muscle and the results compared between adult male (n=9) and female (n=10) mice given LPS or saline (n=10 for both). We measured the maximum M wave amplitude (Mmax), H wave amplitude (Hmax), and latency of both waves. The percentage of motor neurons activated by electrical stimulation of the muscle spindle afferents (Group Ia) was measured by the ratio of Hmax/Mmax. Increased spinal cord excitability would be reflected in a larger Hmax/Mmax, regardless of any concurrent changes in muscle spindle afferent excitability. No difference in Hmax/Mmax was observed with LPS treatment in either sex (M control = 0.27 +/− 0.08; M LPS = 0.26 +/− 0.08; F control = 0.31 +/− 0.19; F LPS = 0.33 +/− 0.13). Similarly, no change in latency of the H wave was observed with LPS treatment in either sex (M control = 6.9 +/−1.1 ms; M LPS = 6.2 +/− 0.8 ms; F control = 6.1 +/− 1.2 ms; F LPS = 5.9 +/− 0.6 ms). Our results indicate that spinal cord excitability of the stretch reflex is unchanged following LPS treatment. Future studies will determine whether stretch reflex strength is decreased following LPS as would be expected since sensory input is decreased but spinal cord excitability is unchanged.Support or Funding InformationThis work was supported by a CSUPERB New Investigator grant (KAW).