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 remain 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 have 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: evaluation of social self-administration as an intervention for chronic pain, and transcriptomic analysis to identify gene expression changes as a result of social interaction. Future research will include miniscope endomicroscopy recordings to visualize cell activity within major brain regions, and comparison of cell ensemble activity between groups of mice will lead to the identification of structures encoding behavioral shifts caused by pain.

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 persistent pain beyond typical recovery window and serves little adaptive function. The negative emotional component inherent in chronic pain contributes to the development of comorbid psychiatric disorders such as depression, social aggression, and social withdrawal. Our research aims to understand the bidirectional relationship between pain and social behavior, by evaluating mechanical sensitivity and changes in social motivation, reward, and interaction following a neuropathic injury. Using social self-administration (SSA), pair-housed mice were placed in operant chambers and underwent voluntary lever press trials for the reward of social interaction with their cage mate. Mice also underwent mechanical hypersensitivity response assays called von Frey where increasing weights of plastic filament were applied to the hind paw. Following baseline von Frey testing and the acquisition of the SSA task, mice then received a spared nerve injury (SNI) to induce neuropathic pain. After surgery recovery, mice were returned to the lever press and von Frey trials at different post-operative windows. Pain sensitivity was determined by the filament weight in which the animal withdrew their paw during von Frey. Changes in social behavior were measured via changes in lever press frequency and interactions during trials. Behavior changes were quantified using Simple Behavior Analysis (SimBA) machine learning to classify interactions during social trials. Once the trials were completed, brain tissue from regions associated with reward and social neural circuitry was collected and investigated using transcriptomic methods. Our data found sexually divergent social adaptations and gene expression following chronic pain. 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.