Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain.

Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit a smaller nucleus accumbens volume, which persists in the chronic phase, compared to healthy controls. The smaller accumbens volume was also observed in a separate cohort of chronic low-back pain patients and was associated with dynamic changes in functional connectivity. At baseline, subacute back pain patients showed altered local nucleus accumbens connectivity between putative shell and core, irrespective of the risk of transition to chronic pain. At follow-up, connectivity changes were observed between nucleus accumbens and rostral anterior cingulate cortex in the patients with persistent pain. Analysis of the power spectral density of nucleus accumbens resting-state activity in the subacute and chronic back pain patients revealed loss of power in the slow-5 frequency band (0.01 to 0.027 Hz) which developed only in the chronic phase of pain. This loss of power was reproducible across two cohorts of chronic low-back pain patients obtained from different sites and accurately classified chronic low-back pain patients in two additional independent datasets. Our results provide evidence that lower nucleus accumbens volume confers risk for developing chronic pain and altered nucleus accumbens activity is a signature of the state of chronic pain.

Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen.

OBJECTIVE: To evaluate intravenous (IV) acetaminophen (APAP) vs oral APAP use as adjunctive analgesics in cholecystectomy patients by comparing associated hospital length of stay (LOS), hospital costs, opioid use, and rates of nausea/vomiting, respiratory depression, and bowel obstruction. METHODS: We conducted a retrospective analysis of the Premier Database (January 2012 to September 2015) including cholecystectomy patients who received either IV APAP or oral APAP. Differences in LOS, hospitalization costs, mean daily morphine equivalent dose (MED), and potential opioid-related adverse events were estimated. Multivariable logistic regression was performed for the binary outcomes and instrumental variable regressions, using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for continuous outcomes. Models were adjusted for patient demographics, clinical risk factors, and hospital characteristics. RESULTS: Among 61,017 cholecystectomy patients, 31,133 (51%) received IV APAP. Subjects averaged 51 and 57 years of age, respectively, in the IV and oral APAP cohorts. In the adjusted models, IV APAP was associated with 0.42 days shorter LOS (95% CI = -0.58 to -0.27; p < .0001), $1,045 lower hospitalization costs (95% CI = -$1,521 to -$569; p < .0001), 2 mg lower average daily MED (95% CI = -3 mg to -0.9 mg; p = .0005), and lower rates of respiratory depression (odds ratio [OR] = 0.89, 95% CI = 0.82-0.97; p = .006), and nausea and vomiting (OR = 0.86, 95% CI = 0.86-0.86; p < .0001). CONCLUSIONS: In patients having cholecystectomy, the addition of IV APAP to perioperative pain management is associated with shorter LOS, lower costs, reduced opioid use, and less frequent nausea/vomiting and respiratory depression compared to oral APAP. These findings should be confirmed in a prospective study comparing IV and oral APAP.