Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of either IL-10 signaling or δOR triggered relapsing pain. Overall, our findings, from electrophysiology, genetic manipulation, flow cytometry, pharmacology, and behavioral approaches, indicate that remission of pain is not simply a return to the naïve state. Instead, remission is an adapted homeostatic state associated with lasting pain vulnerability resulting from persisting neuroimmune interactions within the nociceptive system. Broadly, this sheds light on the elusive mechanisms underlying recurrence a common aspect across various chronic pain conditions.

Factor IX complex for the treatment of severe bleeding after cardiac surgery.

BACKGROUND: Previous reports have been published on the use of recombinant Factor VIIa for intractable bleeding after cardiac surgery; however, there is limited information on the use of Factor IX Complex in this population. METHODS: A retrospective cohort study of adult patients who underwent cardiac surgery and experienced severe postoperative bleeding, defined as a mean chest tube output ≥300 mL/h. Primary outcomes were changes in chest tube output and blood product usage pre- and post-Factor IX Complex administration. RESULTS: Eleven patients received Factor IX Complex for severe postoperative bleeding. The mean dose of Factor IX Complex was 35 (13-52) units/kg. Chest tube output was significantly reduced after Factor IX Complex administration (mean pre-Factor IX Complex 381 ± 49 mL/h, mean post-Factor IX Complex 151 ± 38 mL/h; P = 0.003). Blood product usage decreased after Factor IX Complex but was not statistically significant (mean pre-Factor IX Complex 373 ± 81 mL/h, mean post-Factor IX Complex 212 ± 48 mL/h; P = 0.669). Adverse events included 1 pulmonary embolism (postoperative day 43) and 2 episodes of acute renal failure requiring dialysis (postoperative days 2 and 5). CONCLUSIONS: In this small group of patients, Factor IX Complex effectively controlled severe bleeding after cardiac surgery preventing the need for re-exploration.

Impact of a clinical pharmacy admission medication reconciliation program on medication errors in "high-risk" patients.

BACKGROUND: Medication errors are common upon hospital admission. Clinical pharmacist involvement in medication reconciliation is effective in identifying and rectifying medication errors. However, data is lacking on the economic impact, time requirements, and severity of errors resolved by clinical pharmacists. OBJECTIVE: To determine the incidence of unintended admission medication discrepancies resolved by clinical pharmacists. Secondary objectives were to determine the type of discrepancies, potential severity, proximal cause, and economic impact of this clinical pharmacy program. METHODS: This was a single-center, prospective, observational study conducted at a major teaching medical institution. Following institutional review board approval, data collection was conducted over a 4-week period (August 22, 2011, to September 16, 2011). Descriptive statistical methods were performed for all data analyses. RESULTS: A total of 517 patients involving 5006 medications were included in this study. More than 25% (n = 132) of patients had at least 1 error associated with a medication ordered on hospital admission. Pharmacists resolved a total of 467 admission medication errors (3.5 ± 2.3 errors/patient). The most common type of medication error resolved was medication omission (79.6%). In regard to severity, 46% of medication errors were considered significant or serious. Overall, the mean total time was 44.4 ± 21.8 minutes per medication reconciliation. This clinical pharmacy program was estimated to carry a net present value of $5.7 million over 5 years. CONCLUSION: Clinical pharmacist involvement within a multidisciplinary health care team during the admission medication reconciliation process demonstrated a significant improvement in patient safety and an economic benefit.

Tonic Meningeal Interleukin-10 Upregulates Delta Opioid Receptor to Prevent Relapse to Pain.

Chronic pain often alternates between transient remission and relapse of severe pain. While most research on chronic pain has focused on mechanisms maintaining pain, there is a critical unmet need to understand what prevents pain from re-emerging in those who recover from acute pain. We found that interleukin (IL)-10, a pain resolving cytokine, is persistently produced by resident macrophages in the spinal meninges during remission from pain. IL-10 upregulated expression and analgesic activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of IL-10 signaling or δOR triggered relapse to pain in both sexes. These data challenge the widespread assumption that remission of pain is simply a return to the naïve state before pain was induced. Instead, our findings strongly suggest a novel concept that: remission is a state of lasting pain vulnerability that results from a long-lasting neuroimmune interactions in the nociceptive system.