Interactions between the Nociceptin and Toll-like Receptor Systems.

Nociceptin and the nociceptin receptor (NOP) have been described as targets for treatment of pain and inflammation, whereas toll-like receptors (TLRs) play key roles in inflammation and impact opioid receptors and endogenous opioids expression. In this study, interactions between the nociceptin and TLR systems were investigated. Human THP-1 cells were cultured with or without phorbol myristate acetate (PMA 5 ng/mL), agonists specific for TLR2 (lipoteichoic acid, LTA 10 µg/mL), TLR4 (lipopolysaccharide, LPS 100 ng/mL), TLR7 (imiquimod, IMQ 10 µg/mL), TLR9 (oligonucleotide (ODN) 2216 1 µM), PMA+TLR agonists, or nociceptin (0.01-100 nM). Prepronociceptin (ppNOC), NOP, and TLR mRNAs were quantified by RT-qPCR. Proteins were measured using flow cytometry. PMA upregulated ppNOC mRNA, intracellular nociceptin, and cell membrane NOP proteins (all p < 0.05). LTA and LPS prevented PMA's upregulating effects on ppNOC mRNA and nociceptin protein (both p < 0.05). IMQ and ODN 2216 attenuated PMA's effects on ppNOC mRNA. PMA, LPS, IMQ, and ODN 2216 increased NOP protein levels (all p < 0.05). PMA+TLR agonists had no effects on NOP compared to PMA controls. Nociceptin dose-dependently suppressed TLR2, TLR4, TLR7, and TLR9 proteins (all p < 0.01). Antagonistic effects observed between the nociceptin and TLR systems suggest that the nociceptin system plays an anti-inflammatory role in monocytes under inflammatory conditions

ASA Status, NPPA/NPPB Haplotype and Coronary Artery Disease Have an Impact on BNP/NT-proBNP Plasma Levels.

Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically determined variability in the levels of these biomarkers has been described previously. In the perioperative setting, genetic contribution to NP plasma level variability has not yet been determined. A cohort of 427 patients presenting for non-cardiac surgery was genotyped for single-nucleotide polymorphisms (SNPs) from the NPPA/NPPB locus. Haplotype population frequencies were estimated and adjusted haplotype trait associations for brain natriuretic peptide (BNP) and amino-terminal pro natriuretic peptide (NT-proBNP) were calculated. Five SNPs were included in the analysis. Compared to the reference haplotype TATAT (rs198358, rs5068, rs632793, rs198389, rs6676300), haplotype CACGC, with an estimated frequency of 4%, showed elevated BNP and NT-proBNP plasma concentrations by 44% and 94%, respectively. Haplotype CGCGC, with an estimated frequency of 9%, lowered NT-proBNP concentrations by 28%. ASA classification status III and IV, as well as coronary artery disease, were the strongest predictors of increased NP plasma levels. Inclusion of genetic information might improve perioperative risk stratification of patients based on adjusted thresholds of NP plasma levels

Desire to Receive More Pain Treatment: A Relevant Patient-Reported Outcome Measure to Assess Quality of Post-Operative Pain Management? Results From 79,996 Patients Enrolled in the Pain Registry QUIPS from 2016 to 2019

Acute postoperative pain is frequently evaluated by pain intensity scores. However, interpretation of the results is difficult and thresholds requiring treatment are notwell defined. Additional patientreported outcome measures (PROMs) might be helpful to better understand individual pain experience and quality of pain management after surgery.We used data from the QUIPS pain registry for a cross-sectional study in order to investigate associations between the desire to receive more pain treatment (D2RMPT) with pain intensity ratings and other PROMs. Responses from 79,996 patientswere analyzed, of whom 10.7% reported D2RMPT. A generalized estimating equation Poisson model showed that women had a lower risk ratio (RR) to answer this question with “yes” (RR: .92, P < .001). Factors that increased the risk most were “maximal pain intensity ≥ 6/10 on a numerical rating scale” (RR: 2.48, P < .001) and “any pain interference” (RR: 2.48, P < .001). The largest reduction in risk was observed if patients were “allowed to participate in pain treatment decisions” (RR: .41, P < .001) and if they felt that they “received sufficient treatment information” (RR: .58, P < .001). Our results indicate that the (easily assessed) question D2RMPT gives additional information to other PROMs like pain intensity. The small proportion of patients with D2RMPT (even for high pain scores) opens the discussion about clinicians’ understanding of over- und under-treatment and questions the exclusive use of pain intensity as quality indicator. Future studies need to investigatewhether asking about D2RMPT in clinical routine can improve postoperative pain outcome. Perspective: This article presents characteristics of the patient-reported outcome measure “Desire to receive more pain treatment.” This measure could be used to apply pain treatment in a more individualized way and lead to improved treatment strategies and quality

Cost-effectiveness of the Perioperative Pain Management Bundle a registry-based study.

INTRODUCTION The Perioperative Pain Management Bundle was introduced in 10 Serbian PAIN OUT network hospitals to improve the quality of postoperative pain management. The Bundle consists of 4 elements: informing patients about postoperative pain treatment options; administering a full daily dose of 1-2 non-opioid analgesics; administering regional blocks and/or surgical wound infiltration; and assessing pain after surgery. In this study, we aimed to assess the cost-effectiveness of the Bundle during the initial 24 h after surgery. MATERIALS AND METHODS The assessment of cost-effectiveness was carried out by comparing patients before and after Bundle implementation and by comparing patients who received all Bundle elements to those with no Bundle element. Costs of postoperative pain management included costs of the analgesic medications, costs of labor for administering these medications, and related disposable materials. A multidimensional Pain Composite Score (PCS), the effectiveness measurement, was obtained by averaging variables from the International Pain Outcomes questionnaire evaluating pain intensity, interference of pain with activities and emotions, and side effects of analgesic medications. The incremental cost-effectiveness ratio (ICER) was calculated as the incremental change in costs divided by the incremental change in PCS and plotted on the cost-effectiveness plane along with the economic preference analysis. RESULTS The ICER value calculated when comparing patients before and after Bundle implementation was 181.89 RSD (1.55 EUR) with plotted ICERs located in the northeast and southeast quadrants of the cost-effectiveness plane. However, when comparing patients with no Bundle elements and those with all four Bundle elements, the calculated ICER was -800.63 RSD (-6.82 EUR) with plotted ICERs located in the southeast quadrant of the cost-effectiveness plane. ICER values differ across surgical disciplines. CONCLUSION The proposed perioperative pain management Bundle is cost-effective. The cost-effectiveness varies depending on the number of implemented Bundle elements and fluctuates across surgical disciplines

PROSPECT-Leitlinien für die onkologische Mammachirurgie: Hilfreiche Empfehlungen trotz vieler offener Fragen

Onkologische Brustchirurgie ist mit signifikantem akutem und chronischem postoperativem Schmerz assoziiert. Ein systematisches Review zu analgetischen Strategien wurde 2006 erarbeitet, jedoch bestehen seitdem zahlreiche neue analgetische Regime, insbesondere regionalanästhetische Techniken (z. B. Blöcke der pektoralen Nerven und Erector-spinae-Blöcke)

Pain-related functional interference in patients with chronic neuropathic postsurgical pain: an analysis of registry data.

Although chronic postsurgical pain (CPSP) is a major health care problem, pain-related functional interference has rarely been investigated. Using the PAIN OUT registry we evaluated patients' pain-related outcomes on the first postoperative day, and their pain-related interference with daily living (Brief Pain Inventory) and neuropathic symptoms (DN4: douleur neuropathique en 4 questions) at six months after surgery. Endpoints were pain interference total scores (PITS) and their association with pain and DN4 scores. Furthermore, possible risk factors associated with impaired function at M6 were analyzed by ordinal regression analysis with PITS groups (no to mild, moderate and severe interference) as a dependent three-stage factor. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Of 2,322 patients, 15.3% reported CPSP with an average pain score ≥3 (NRS 0-10). Risk for a higher PITS group increased by 190% (OR (95%-CI): 2.9 (2.7-3.2); p<0.001) in patients with, compared to without CPSP. A positive DN4 independently increased risk by 29% (1.3 (1.12-1.45), p<0.001). Pre-existing chronic pain (3.6 (2.6-5.1); p<0.001), time spent in severe acute pain (2.9 (1.3-6.4); p=0.008), neurosurgical back surgery in males (3.6 (1.7-7.6); p<0.001) and orthopedic surgery in females (1.7 (1.0-3.0); p=0.036) were the variables with strongest association with PITS. PITS might provide more precise information about patients' outcomes than pain scores only. As neuropathic symptoms increase PITS, a suitable instrument for their routine assessment should be defined