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Introduction: Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. Methods: A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS—needle electrodes) and transcutaneous (tVNS—surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. Results: A total of n= 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges’ g/mean difference of − 1.95 (95% confidence interval [CI]: − 3.94 to 0.04, p= 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (− 5.40 [− 8.94; − 1.85] vs. − 1.00 [− 1.55; − 0.44]; p= 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with − 0.70 [− 2.34; 0.93] (p= 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated. Conclusion: This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes.

The injection of low-dose opioids (mainly buprenorphine or sufentanil) to different sympathetic ganglia has been termed “ganglionic local opioid analgesia” (GLOA). This form of therapy has been successfully used for numerous, often protracted diseases that severely impair the patient’s quality of life, such as trigeminal neuralgia. For example, as part of a multimodal approach for pain management, GLOA at the superior cervical ganglion should be considered for pain treatment in patients suffering from trigeminal neuralgia with high pre-procedural pain scores.

Introduction: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice. Methods: The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate. Results: A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment. Discussion: Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions. Conclusions: l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst. Graphical Abstract:

CT-guided coeliac plexus neurolysis is considered effective at controlling pain in patients with intra-abdominal malignancies. Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control.

In patients with intra-abdominal malignancy-related abdominal pain, CT-guided coeliac plexus neurolysis is a safe and effective procedure. It can provide long-lasting significant relief of background pain and breakthrough cancer pain. As part of a multimodal approach, coeliac plexus neurolysis should be considered as an earlier option for pain management in patients with intractable abdominal cancer pain.

Dysphagia is common in intensive care unit (ICU) patients, yet it remains underrecognized and often unmanaged despite being associated with life-threatening complications, prolonged ICU stays and hospitalization.

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today's scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.

Intermittent hypoxic–hyperoxic training (IHHT) may complement a multimodal training intervention (MTI) for improving cognitive function and exercise tolerance in geriatric patients.

Transdermal buprenorphine has been shown to be effective in managing moderate-to-severe cancer pain and severe pain that is unresponsive to nonopioid analgesics. In clinical trials, it provided better pain relief than placebo, despite a higher consumption of rescue analgesia by placebo patients. Analgesia was rated as satisfactory or better by 90% of patients in a long-term follow-up study and 94.6% considered the buprenorphine matrix patch to be user friendly. Transdermal buprenorphine is well tolerated; most adverse events are transient local reactions to the patch or systemic effects typical of treatment with opioids. Even in opioid-experienced volunteers, buprenorphine does not cause respiratory depression at doses up to 70-times higher than those used for analgesia. No problems have been encountered when switching from another opioid to transdermal buprenorphine, or in combining the buprenorphine patch with intravenous morphine or tramadol for breakthrough pain. There is a growing body of evidence that transdermal buprenorphine may be particularly useful for managing neuropathic pain. Most notably, it appears to be effective in treating hyperalgesic states and syndromes characterized by pronounced central sensitization.

ABSTRACTObjective:The objective of this post-marketing surveillance study was to collect effectiveness and safety data on the labelled use of buprenorphine transdermal patches (Transtec*) under routine clinical conditions. *Transtec is a registered trademark of Grünenthal GmbH, Aachen, GermanyResearch design and methods:For this open, observational study, patients with moderate to severe cancer or non-cancer pain requiring treatment with an opioid analgesic were recruited at hospitals, outpatient clinics and general practitioners’ practices in Germany. Buprenorphine transdermal patches (35 µg/h, 52.5 µg/h or 70 µg/h) were prescribed at physicians’ discretion in accordance with the product's Summary of Product Characteristics (SmPC). Patients assessed their pain relief as ‘very good’, ‘good’, ‘satisfactory’, ‘poor’ or ‘no effect’. Investigators were instructed to report all adverse events throughout the observation period. On completion, effectiveness and tolerability were evaluated for the overall study population, cancer and non-cancer patients, and patients < 70 years and ≥ 70 years. Other analyses assessed pain relief with respect to previous opioid treatment and increased patch strength, and in patients who remained on their original dose. The total observation time was 9 months, and the average individual documented treatment time was 60.8 days.Results:A total of 13 179 patients were evaluated; 3690 (28%) with cancer pain and 9489 (72%) with non‐cancer pain. The most frequent diagnoses in non‐cancer patients were musculoskeletal disorders (77%) and neuropathy (23%). In the great majority of cases (78%), treatment was started with the 35 µg/h patch. The initial dose needed to be increased subsequently only in about 18% of subjects. Buprenorphine transdermal patches provided effective, sustained and dose-dependent analgesia in patients with cancer and non‐cancer pain, irrespective of the patients’ age or pain syndromes. Whereas good or very good pain relief was documented only for 6% of the patients with the initial assessment, this percentage increased to 71% at the first follow‐up and 80% at the final assessment. Fewer than 5% of subjects discontinued treatment owing to unsatisfactory pain relief. Altogether, adverse events were documented for 2874 patients (22%), whereas a relationship with transdermal buprenorphine (adverse drug reactions) was assumed for only 10% (2220 adverse drug reactions in 1330 patients). The tolerability profile was as expected for an opioid and did not vary to a relevant extent with either the patient's age or the cause of pain (cancer or non‐cancer). No evidence emerged of any previously unknown side effects.Conclusions:Buprenorphine transdermal patches are well tolerated and effective in the treatment of chronic cancer and non‐cancer pain, irrespective of the patients’ age. There was no clinically relevant development of tolerance.

A neonate with chromosomal 9 abnormality and omphalocele received a lumbar epidural catheter after laparotomy. Several attempts were needed to establish this catheter. Bleeding occurred from the operative wound after surgery. Using an epidural infusion with ropivacaine 0.1% for 48 h postoperative pain relief was sufficient. Four days after epidural catheter removal, dysfunction of the sacral parasympathetic nerves was noted. Motor and sensor function of the lower limbs were unaffected. Magnetic resonance imaging showed a localized intraspinal haematoma in the lower lumbar region.

The aim of this randomised double-blind study was to assess the analgesic efficacy of intraarticular neostigmine applied postoperatively following arthroscopic procedures of the knee joint. Patients, aged 19 to 70 years, were randomised into two groups. Group I received 500 μg of neostigmine + 10 ml NaCl intraarticularly at the end of surgery, prior to the arthroscope being removed. Group II received 10 ml of physiologic saline intraarticularly. Pain scores were assessed postoperatively using the visual analogue scale (0=no pain, 10=unbearable pain at rest or with activity). In addition, side effects and sedation scores were recorded. Vital signs and the above scores were recorded before the first analgesic request and at 1, 2, 3, 6, 9, 12, 18 and 24 hours postoperatively. For rescue medication patients received a loading dose of morphine hydrochloride postoperatively, followed by patient controlled analgesia.

The case of a 680 g premature baby who developed massive spontaneous liver haemorrhage during laparotomy for necrotizing enterocolitis is reported. The infant survived due to rapid and massive fluid administration, including transfusion of large volumes of blood and blood products, in combination with high dose inotropic support and the surgical use of packing with thrombostatic sponges. Good venous access, including two central venous lines, turned out to be very useful.