Effects of Early Life Stress or Inflammation on Spinal Dorsal Horn Neuronal Responses to Perineal Mechanical Stimulation in Male Mice

This study characterized responses of dorsal horn neurons to perineal mechanical stimulation in adult male C57Bl/6J mice after neonatal maternal separation (NMS) or neonatal pelvic inflammation (NPI). For NMS, pups were removed from their home cage 4 hrs daily on P1-P21; controls were left undisturbed. For NPI, pups were anesthetized on P12 and Zymosan A (10 mg/ml, 20 ul) was injected into the pelvic floor musculature (Zymo); controls were exposed to anesthesia (Anes). At 12-15 weeks of age, mice were anesthetized and prepared for in vivo spinal recordings. Single-unit extracellular recordings were discriminated from background, converted into uniform pulses, and saved to computer as peristimulus-time histograms. Von Frey filaments (15-180 g) were applied to the perineum and evoked activity was calculated as total activity during 10-sec stimulus minus spontaneous activity in 10-sec prior to stimulus. Responses to non-noxious input and to a heterotopic noxious conditioning stimulus (HCNS) were determined for each neuron (Type I inhibited >20%, all others Type II). A total of 23 control and 17 NMS neurons were recorded. Chi-square showed no difference in the proportions of wide dynamic range (WDR) and nociceptive specific (NS) neurons between groups. Linear regression showed no difference in the slopes for WDR or NS neurons between groups. The proportion of Type I neurons was significantly reduced by NMS (Chi-square, p<0.05). A total of 9 Anes and 17 Zymo neurons were recorded. Chi-square showed no difference in the proportions of WDR and NS neurons, but the slopes for WDR (p<0.05) and NS (p<0.01) neurons were different between groups. NPI did not change the proportions of Type I neurons (Chi-square, NS). Early life stress and inflammation differentially affect subpopulations of dorsal horn neurons responsive to UBD. Changes in gain and the effect of HNCS reflect alterations in spinal transmission consistent with development of hypersensitivity.