Modulation of nociception by social factors in rodents: Contribution of the opioid system

Rationale: The opioid system is involved in the regulation of several behavioral and physiological responses, controlling pain, reward, and addictive behaviors. Opioid administration, depending on drugs and doses, usually affects sociability reducing interactions between conspecifics, whereas some affiliative behaviors such as sexual activity, social grooming, and play behavior increase the endogenous opioid activity. Objectives: The possible interaction between endogenous opioids released during socio/sexual behavior and their analgesic effect on pain response is reviewed in the rodent literature. Results: Direct evidence for socially mediated opioid changes resulting in increase in nociceptive threshold derives from studies exploring the effects of defeat experiences, social isolation, maternal, sexual behavior, and social reunion among kin or familiar animals in laboratory rodents. Indirect evidence for endogenous activation of the opioid system, possibly affecting pain sensitivity, derives from studies investigating the relevance of natural social reward using the conditioned place preference protocols or analyzing ultrasonic vocalizations associated to positive affective contexts. Finally, genetic and epigenetic factors that affect the opioid system during development are reported to be involved in modulating the response to social stimuli as well as nociception. Conclusions: All studies highlight the relevance of affiliative contact behavior between conspecifics that is responsible for the activation of the endogenous mu-opioid system, inducing nociceptive threshold increase.