Earlier observations show that social stress has a strong effect on the autonomic nervous system. Moreover, exposure to social stress may be associated with low-grade systemic inflammation and hyperalgesia. In the present study, we examined the role of key HPA axis regulators and circulating microRNAs (miRNAs) in these processes. The relationship between social stress, upregulation of circulating miRNAs and change in behavior was investigated using a resident-intruder paradigm. Long Evans rats were used as residents and Sprague Dawley rats were used as intruders. The intruder rats were exposed to dominant resident rats one hour daily for one week. Bodyweight- and behavior changes were measured in order to validate the paradigm. Blood samples were taken throughout the stress period and tissue harvesting was done post-mortem. Gene expression and miRNA levels were investigated using qPCR. Extracellular single cell recordings were used to study the effect of ACTH on spinal nociceptive signaling. THP-1 cells were transfected with miRNAs to examine their effect on cytokine release. Reduced weight gain was observed in the intruder rats exposed to social stress. Pituitary POMC and adrenal Nr3c1 mRNA were also downregulated. Single cell electrophysiological recordings showed that ACTH applied onto the dorsal horn reduced nociceptive signaling. Interestingly, social stress increased expression of miR-146a, miR-30c and miR-223 in plasma. In THP-1 cells, miR-223 transfection seem to increase TNF expression and release. Taken together, the present thesis showed that social stress affects HPA axis function, nociception and plasma miR-146a, miR-30c and miR-223 expression. How the miRNAs affect the immune system and the brain remains to be investigated.