Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture.

Survivors of sepsis often face long-term sequelae after intensive care treatment. Compared to the period of hospitalization, little is known about the ambulatory healthcare utilization in sepsis patients. The study evaluated healthcare utilization and associated costs of sepsis care including allied health professions after initial hospitalization. Methods: Secondary analysis was performed on data in 210 sepsis patients prospectively enrolled from nine intensive care study centers across Germany. Data was collected via structured surveys among their Primary care (Family-) physicians (PCPs) within the first month after discharge from ICU (baseline) and again at 6, 12 and 24 months after discharge, each relating to the period following the last survey. Costs were assessed by standardized cost unit rates from a health care system’s perspective. Changes in healthcare utilization and costs over time were calculated using the Wilcoxon rank-sum test. Results: Of the 210 patients enrolled, 146 (69.5%) patients completed the 24 months follow-up. In total, 109 patients were hospitalized within the first 6 months post-intensive care. Mean total direct costs per patient at 0–6 months were €17,531 (median: €6047), at 7–12 months €9029 (median: €3312), and at 13–24 months €18,703 (median: €12,828). The largest contributor to the total direct costs within the first 6 months was re-hospitalizations (€13,787 (median: €2965). After this first half year, we observed a significant decline in inpatient care costs for re-hospitalizations (p < 0.001). PCPs were visited by more than 95% of patients over 24 months. Conclusions: Sepsis survivors have high health care utilization. Hospital readmissions are frequent and costly. Highest costs and hospitalizations were observed in more than half of patients within the first six months post-intensive care. Among all outpatient care providers, PCPs were consulted most frequently. Clinical impact: Sepsis survivors have a high healthcare utilization and related costs which persist after discharge from hospital. Within outpatient care, possible needs of sepsis survivors as physiotherapy or psychotherapy seem not to be met appropriately. Development of sepsis aftercare programs for early detection and treatment of complications should be prioritized.

Background: Evidence-based psychological interventions for posttraumatic stress disorder (PTSD) are available in specialized settings, but adequate care in primary care is often lacking. The aim of this systematic review was to determine the effectiveness of psychological interventions for PTSD involving primary care physicians (PCPs) and to characterize these interventions as well as their providers. Method: A systematic review and meta-analyses of randomized controlled trials (RCTs). Primary outcome were symptoms of PTSD. Results: Four RCTs with a total of 774 patients suffering from PTSD symptoms were included, all applying cognitive behavioural based interventions. Three studies with psychological interventions being conducted by case managers were pooled in a meta-analysis. Interventions were not effective in the short term (0-6 months; SMD, − 0.1; 95% CI, − 0.24-0.04; I 2 = 0%). Only two studies contributed to the meta-analysis for long term (12-18 months) outcomes yielding a small effect (SMD, − 0.23; 95% CI, − 0.38-0.08; I 2 = 0%). Conclusions: Psychological interventions for PTSD in primary care settings may be effective in the long term but number and quality of included studies was limited so the results should be interpreted with caution.