SUMMARYNeuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV inter-neuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.

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BACKGROUND:Abdominal gunshot wounds (GSWs) require rapid assessment and operative intervention to reduce the risk of death and complications. We sought to determine if time to the operating room (OR) might be a useful process measure for the assessment of trauma care quality. We evaluated the facility benchmark time to OR for patients with serious injury and whether this was associated with lower rates of complications and mortality. METHODS:We evaluated time to OR for adult patients with an abdominal GSW presenting in shock to American College of Surgeons Trauma Quality Improvement Program centers from 2015 to 2020. We calculated the 75th percentile time to the OR for each center and characterized centers as average, slow, or fast. We compared patient and facility characteristics across outlier status, as well as risk-adjusted complications and mortality using hierarchical multivariable logistic regression models. RESULTS:There were 4,027 patients in 230 centers that met the inclusion criteria. Mortality was 28%. There were 61 (27%) fast and 52 (23%) slow centers. The median time for slow centers was 83 minutes (68-94 minutes) compared with fast centers, 35 minutes (32-38 minutes). Injury Severity Score and emergency department vital signs were similar across centers. Fast hospitals had higher total case volumes, more cases per surgeon, and were more likely to be Level I centers. Patients cared for in these centers had similar riskadjusted rates of complications and mortality. CONCLUSION:Time to OR for patients with abdominal GSWs and shock might be a useful process measure to evaluate rapid decision making and OR access. Surgeon and center experience as measured by annual case volumes, coupled with a rapid surgical response required through Level I trauma center standards might be contributory. There was no association between outlier status and complications or mortality suggesting other factors apart from time to the OR are of greater significance.