The sensation of acute pain is fundamental to survival, indicating tissue damage that motivates an animal to engage in adaptive protective behaviors. Chronic pain, however, is pain that persists beyond the typical recovery window and serves little adaptive function. Due to the negative affective component inherent in chronic pain, it has been shown to contribute to the development of comorbid psychiatric disorders such as depression, social aggression, and social withdrawal. Our research aims to understand how acute and chronic pain affects social reward, motivation, and behavior. Our experiments used social self-administration (SSA), where pair-housed mice were placed in operant chambers and underwent voluntary lever press trials for the reward of social interaction with their cagemate. Following the acquisition of the SSA task, male and female mice then received a spared nerve injury (SNI) to induce neuropathic pain. Following recovery from the SNI surgery, experimental mice were returned to the lever press trials at different post-operative windows to simulate acute and persistent pain windows. Changes in social behavior were measured via changes in lever press frequency and interactive behavior during trials. Our data shows that male and female mice who underwent SSA trials immediately following nerve ligation maintained normal levels of social interaction. In contrast, female experimental animals that began SSA at a delayed time point, simulating persistent pain, lever pressed significantly less for a social partner compared to their respective control group. Conversely, male experimental animals at the delayed time point displayed high lever pressing behavior for a social partner. This data points towards divergent social adaptations following pain due to the sex of the experimental mice. Future experiments will further delineate these sex-specific adaptations following a traumatic injury. This research can inform social intervention as an adjunct or alternative treatment to pharmacological pain intervention and its comorbidities.

Social interactions in humans have shown to improve pain outcomes and diminish the development of mechanical hypersensitivity (allodynia) following injury. This effect is known as social buffering of pain; however, the underlying mechanisms are not well understood. Prior preclinical studies focused on forced social interactions between unfamiliar mice, lacking translational value to patients. To fill this gap, our research explores how volitional social behavior shifts pain sensitivity and affect following a neuropathic injury. Volitional interaction is key to socialization as individuals usually socialize because they want to, not due to force, which makes studying how mice voluntarily interact with each other important. To determine how volitional social interaction impacts both sensory and affective (emotional) components of pain, we use male and female mice who have received a spared nerve injury (SNI). Trained in social self-administration, mice learn to lever-press to engage with a familiar conspecific. Mice are then tested in von Frey where thin plastic filaments of increasing weights are applied to the mouse hind paw before and after SNI. These filaments do not cause pain, rather elicit a pain response of withdrawing the paw. To determine sensory sensitivity, the weight when the animal's paw is withdrawn is recorded as percent change from baseline. To determine changes in affective pain, the amount of time the animals hold their paw up, following withdrawal, is recorded as percent change from baseline. We found that male and female mice show significant attenuation in their mechanical hypersensitivity following volitional social interaction compared to mice deprived of volitional social interaction. Males show even less mechanical sensitivity, indicating that males may be more impacted by social analgesia than females. Understanding the divergent responses between male and female mice and the role of volitional social interaction in pain modulation, offers potential avenues for developing novel therapeutic strategies.

The mechanisms guiding the sensory detection of pain and the subsequent sensitization of damaged tissue to mechanical and thermal stimuli are relatively well understood. However, mechanisms guiding the transformation of nociception into the negative feelings associated with pain remains largely unknown. This affective component, notably in chronic pain, translates into an intense emotional impact on patients and can contribute to the development of comorbid psychiatric disorders. The elderly population has a propensity to be socially isolated and face exacerbated effects of chronic pain. In 2021, an estimated 20.9% of U.S adults suffer from chronic pain with persons over 65 years of age having the greatest propensity of acquiring the disease. Due to this, clinical intervention models call for a more holistic approach to pain intervention that incorporates lifestyle and nutritional factors, extending beyond pharmacological treatments. One of these promising non-pharmacological interventions is positive social interaction, which has been shown to alleviate pain and suffering. Several studies show that humans who maintain strong social bonds recover from injuries faster than people without them. However, it has not yet been evaluated the extent to which this phenomenon occurs in geriatric animals and its relative efficacy as a social intervention to alleviate chronic pain in injured mice. My project seeks to gauge whether social intervention can alleviate chronic pain symptoms in aged mice and to unveil the underlying mechanisms guiding these successful non-pharmacological treatments. I will achieve this through two aims: an evaluation of social self administration as an intervention for chronic pain, and histological analysis to identify gene expression changes as a result of social interaction. Future research will include mini-scope endomicroscopy recordings to visualize communication among major brain regions, and comparison of cell ensemble activity between groups of mice will lead to the identification of relevant neural ensembles and molecules.