Nociceptive sensitivity in rats under chronic unpredictable mild stress following administration of innate immune response receptor blocker

Objective. To analyze nociceptive sensitivity in rats under chronic unpredictable mild stress (CUMS) following pre-administration of innate immune response receptor blocker. Material and methods. The study was conducted on adult male Wistar rats. To investigate the effects of prolonged stress exposure, a CUMS model was applied for 1—4 weeks. Prior to CUMS, the animals were administered either 1% dimethyl sulfoxide or selective Toll-like receptor 4 (TLR4) antagonist via intraperitoneal injection. Perceptual component was assessed by tail-withdrawal response latency, emotional component — by vocalization threshold. Results. In early stages of CUMS (1—2 weeks), prior systemic administration of a TLR4 blocker prevents attenuation of perceptual component of nociception in animals caused by repeated stressors. In delayed period (3 weeks), TLR4 blocker injection is followed by weakened perceptual component of nociception relative to that in animals exposed to isolated stressors. Intensity of emotional component of nociceptive sensitivity in later stages (3 weeks) of repeated stressors under prior TLR4 blocker administration is lower than baseline state, as well as compared to animals subjected to isolated CUMS. Emotional component of nociceptive sensitivity did not increase in delayed phase of CUMS (4 weeks) after prior TLR4 blocker administration. Conclusion. Our data can inspire new approaches to identifying new targets for drug aimed at preventing or correcting stress-induced changes in pain sensitivity.