A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.

Chronic primary pain conditions (CPPCs) affect over 100 million Americans, predominantly women. They remain ineffectively treated, in large part because of a lack of valid animal models with translational relevance. Here, we characterized a CPPC mouse model that integrated clinically relevant genetic (catechol-O-methyltransferase; COMT knockdown) and environmental (stress and injury) factors. Compared with wild-type mice, Comt+/- mice undergoing repeated swim stress and molar extraction surgery intervention exhibited pronounced multisite body pain and depressive-like behavior lasting >3 months. Comt+/- mice undergoing the intervention also exhibited enhanced activity of primary afferent nociceptors innervating hindpaw and low back sites and increased plasma concentrations of norepinephrine and pro-inflammatory cytokines interleukin-6 (IL-6) and IL-17A. The pain and depressive-like behavior were of greater magnitude and longer duration (≥12 months) in females versus males. Furthermore, increases in anxiety-like behavior and IL-6 were female-specific. The effect of COMT genotype × stress interactions on pain, IL-6, and IL-17A was validated in a cohort of 549 patients with CPPCs, demonstrating clinical relevance. Last, we assessed the predictive validity of the model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were effective in spared nerve injury and complete Freund's adjuvant models, respectively, but failed in clinical trials. Yet, pain in the CPPC model was alleviated by the beta-3 adrenergic antagonist SR59230A. Thus, the CPPC mouse model reliably recapitulates clinically and biologically relevant features of CPPCs and may be implemented to test underlying mechanisms and find new therapeutics.

A Tailored SMS Text Message-Based Intervention to Facilitate Patient Access to Referred Community-Based Social Needs Resources: Protocol for a Pilot Feasibility and Acceptability Study.

BACKGROUND: Health care providers are increasingly screening patients for unmet social needs (eg, food, housing, transportation, and social isolation) and referring patients to relevant community-based resources and social services. Patients' connection to referred services is often low, however, suggesting the need for additional support to facilitate engagement with resources. SMS text messaging presents an opportunity to address barriers related to contacting resources in an accessible, scalable, and low-cost manner. OBJECTIVE: In this multi-methods pilot study, we aim to develop an automated SMS text message-based intervention to promote patient connection to referred social needs resources within 2 weeks of the initial referral and to evaluate its feasibility and patient acceptability. This protocol describes the intervention, conceptual underpinnings, study design, and evaluation plan to provide a detailed illustration of how SMS technology can complement current social needs screening and referral practice patterns without disrupting care. METHODS: For this pilot prospective cohort study, this SMS text message-based intervention augments an existing social needs screening, referral, and navigation program at a federally qualified health center. Patients who received at least one referral for any identified unmet social need are sent 2 rounds of SMS messages over 2 weeks. The first round consists of 5-10 messages that deliver descriptions of and contact information for the referred resources. The second round consists of 2 messages that offer a brief reminder to contact the resources. Participants will evaluate the intervention via a survey and a semistructured interview, informed by an adapted technology acceptance model. Rapid qualitative and thematic analysis will be used to extract themes from the responses. Primary outcomes are implementation feasibility and patient acceptability. Secondary outcomes relate to intervention effectiveness: self-reported attempt to connect and successful connection to referred resources 2 weeks after the initial referral encounter. RESULTS: The study received regulatory approval in May 2021, and we anticipate enrolling 15-20 participants for this initial pilot. CONCLUSIONS: This protocol presents detailed implementation methods about a novel automated SMS intervention for social care integration within primary care. By sharing the study protocol early, we intend to facilitate the development and adoption of similar tools across different clinical settings, as more health care providers seek to address the unmet social needs of patients. Study findings will provide practical insights into the design and implementation of SMS text message-based interventions to improve social and medical care coordination. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37316.