Ketamine as Treatment for Cluster Headache: A Systematic Review of Literature and a Case Series.

INTRODUCTION: Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data. METHODS: In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients' experience of treatment success and quality of life. RESULTS: The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment. CONCLUSION: Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged.

This article discusses the potential use of ketamine for the treatment of cluster headache, a severe neurological condition that can have a significant impact on patients' quality of life. The authors conducted a systematic review of the existing literature on ketamine for the treatment of cluster headache. Additionally, they also presented their own cohort study of ten patients receiving ketamine infusions. The review of the literature revealed four reports with a total of 68 patients, all of which were uncontrolled case series. While the current literature suggests that ketamine may be effective in relieving cluster headache symptoms, the heterogeneity of treatment regimens and reported outcomes makes it difficult to draw definitive conclusions. The authors' own cohort study found that patients were very satisfied with ketamine treatment, indicating a potential benefit of this approach. However, due to the limited evidence available, further research, including randomized controlled trials, is needed to better understand the efficacy of ketamine in the treatment of cluster headaches.

The Dose-Response Relationship between Opioid Agonist Therapy and Alterations in Pain Pathways in Patients with Opioid Use Disorders: A Cross-Sectional Study.

INTRODUCTION: The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. OBJECTIVE: The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. METHODS: This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. RESULTS: A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. CONCLUSION: The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.

The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers-A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

Palmitoylethanolamide (PEA) is marketed as a "dietary food for special medical purposes". Its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects make PEA an interesting substance in pain management. However, the underlying analgetic mechanisms have not yet been investigated in humans. The aim of our study is to provide a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches. In this randomized, placebo-controlled, double-blinded crossover trial, 14 healthy volunteers were included. PEA (3 × 400 mg per day) or placebo were taken for 4 weeks. Our study investigated the mode of action of PEA using an established pain model, "Repetitive phasic heat application", which is well-suited to investigate analgesic and anti-hyperalgesic effects in healthy volunteers. Parameters for peripheral and central sensitization as well as for pain modulation were assessed. Repetitive heat pain was significantly decreased, and the cold pain tolerance was significantly prolonged after the PEA treatment. The pressure pain tolerance and the conditioned pain modulation were increased after the PEA treatment. The wind-up ratio and the average distance of allodynia were significantly decreased after the PEA treatment. The heat pain tolerance was significantly higher after the PEA treatment. The present study has demonstrated that PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms as well as in pain modulation.

Perioperative use of physostigmine to reduce opioid consumption and peri-incisional hyperalgesia: a randomised controlled trial.

BACKGROUND: Several studies have shown that cholinergic mechanisms play a pivotal role in the anti-nociceptive system by acting synergistically with morphine and reducing postoperative opioid consumption. In addition, the anti-cholinesterase drug physostigmine that increases synaptic acetylcholine concentrations has anti-inflammatory effects. METHODS: In this randomised placebo-controlled trial including 110 patients undergoing nephrectomy, we evaluated the effects of intraoperative physostigmine 0.5 mg h-1 i.v. for 24 h on opioid consumption, hyperalgesia, pain scores, and satisfaction with pain control. RESULTS: Physostigmine infusion did not affect opioid consumption compared with placebo. However, the mechanical pain threshold was significantly higher (2.3 [sd 0.3]) vs 2.2 [0.4]; P=0.0491), and the distance from the suture line of hyperalgesia (5.9 [3.3] vs 8.5 [4.6]; P=0.006), wind-up ratios (2.2 [1.5] vs 3.1 [1.5]; P=0.0389), and minimum and maximum postoperative pain scores at 24 h (minimum 1.8 [1.0] vs 2.4 [1.2]; P=0.0451; and maximum 3.2 [1.4] vs 4.2 [1.4]; P=0.0081) and 48 h (minimum 0.9 [1.0] vs 1.6 [1.1]; P=0.0101; and maximum 2.0 [1.5] vs 3.2 [1.6]; P=0.0029) were lower in the study group. Pain Disability Index was lower and satisfaction with pain control was higher after 3 months in the physostigmine group. CONCLUSIONS: In contrast to previous trials, physostigmine did not reduce opioid consumption. As pain thresholds were higher and hyperalgesia and wind-up lower in the physostigmine group, we conclude that physostigmine has anti-hyperalgesic effects and attenuates sensitisation processes. Intraoperative physostigmine may be a useful and safe addition to conventional postoperative pain control. CLINICAL TRIAL REGISTRATION: EudraCT number 2012-000130-19.

The Effect of Low-Level Light Therapy on Capsaicin-Induced Peripheral and Central Sensitization in Healthy Volunteers: A Double-Blinded, Randomized, Sham-Controlled Trial.

INTRODUCTION: Several clinical trials have demonstrated that low-level light therapy (LLLT), a method of photobiomodulation, is an effective analgetic treatment. However, the mechanism of action has not yet been finally clarified. In particular, unanswered questions include whether it only affects peripheral or whether it also affects the spinal or supraspinal level. This study aimed to evaluate the effect of low-level light therapy on primary and secondary hyperalgesia in a human pain model. METHODS: This study was planned as a randomized, sham-controlled, and double-blinded trial with repeated measures within subject design. Capsaicin was applied on both forearms of ten healthy volunteers to induce peripheral and central sensitization. One forearm was treated with low-level light therapy; the other served as sham control. RESULTS: Low-level light therapy significantly increased the mechanical pain threshold, heat pain threshold, and decreased pain intensity. CONCLUSIONS: Our data indicate that low-level light therapy is effective at reducing the heat and mechanical pain threshold in a human pain model, pointing to a significant modulating effect on peripheral and central sensitization. These effects-especially in the absence of reported side effects-make low-level light therapy a promising tool in pain management. The application of low-level light therapy to treat chronic pain should be considered for further clinical trials.

Impact of a new cryotherapy device on early rehabilitation after primary total knee arthroplasty (TKA): a prospective randomised controlled trial.

BACKGROUND: The aim of this prospective, randomised and single blinded study was to evaluate the efficiency and safety of a new cryotherapy device in patients undergoing unilateral, primary total knee arthroplasty (TKA). Our hypothesis was that patients administered to the new cryotherapy device would perform better than patients receiving a conventional standard cold therapy regimen. METHODS: Ninety-seven patients were randomised into two groups receiving either the cTreatment® (new cryotherapy device) or the standard cold therapy protocol (including cold pack application for six days after the surgical intervention). We evaluated the following endpoints consisting of range of motion (ROM), pain intensity, and knee girth on admission day and the second, fourth, and sixth post-operative day (POD). RESULTS: A statistically significant benefit of the new cryotherapy device was detected regarding the ROM on the sixth POD with an average gain of 7 degrees (p = 0.021). Pain in the numeric rating scale (NRS) score in motion was significantly lower in the cTreatment® group on the second POD (p = 0.034). There were no statistically significant differences between groups regarding the NRS in rest, patient controlled analgesia (PCA) consumption, and girth measurements. No adverse effects were observed in both study groups. CONCLUSION: The new computer-controlled cooling therapy device provides benefits in terms of early post-operative remobilisation with respect to ROM and pain, which might be attributed to a reduced inflammatory response, as well as reduced secretion and bleeding. The cTreatment® system appears to be a safe and efficient procedure.

The Effect of the Modified Lateral Suprascapular Block on Shoulder Function in Patients With Chronic Shoulder Pain.

BACKGROUND: Suprascapular nerve block (SSNB) is commonly used in pain therapy for patients with chronic shoulder pain. The effect of SSNB on shoulder function has, however, not been investigated so far. If in shoulder function, i.e. the range of motion is increased after application of the nerve block, it can be expected that subsequent physiotherapy, besides being less painful, is also more effective in terms of restoring shoulder mobility. OBJECTIVES: Our aim was to evaluate the effect of SSNB on shoulder function, in patients with chronic shoulder pain. PATIENTS AND METHODS: Patients were evaluated using the Constant-Murley Score (CMS) and number rating scale values for pain. The SSN was blocked using the Feigl approach, with 5 ml ropivacaine 0.5%. Shoulder function and pain were assessed 60 minutes and 24 hours after the block. RESULTS: Totally, 20 patients completed the study. The CMS and pain scores significantly improved after the block. CONCLUSIONS: The use of the modified lateral SSNB of Feigl significantly reduces pain and increases shoulder function, in chronic shoulder pain.

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery.

BACKGROUND: Octreotide acetate is an 8-amino-acids synthetic octapeptide analogue of somatostatin with much-enhanced duration of action and lower incidence of side effects. We assessed the utility of using intravenous octreotide as an adjuvant to opioid analgesia that might exert a post-operative opioid-sparing effect. METHODS: Forty-four patients were randomly allocated, to receive either a placebo or intraoperative octreotide 0.33 microg kg(-1)h(-1) intravenous infusion that was maintained in the post-operative period. Patients received for post-operative analgesia an intravenous piritramide patient controlled analgesia (PCA), set to deliver a piritramide 0.02 mgkg(-1) dose. RESULTS: Two-way ANOVA revealed significantly fewer (P=0.0003) mean+/-SD weighted piritramide dose requirements in the octreotide group (19.5+/-6.3 microg kg(-1)h(-1)) than in the control group (35.7+/-8.2 microg kg(-1)h(-1)). Dunnett's two-sided multiple-comparison post hoc test revealed a significant difference between the two groups during the first 22 post-operative hours, following which there were no differences between the two groups. There were no significant differences over time in the mean arterial pressure (P=0.722), heart rate (P=0.579) and respiratory rate (P=0.823) between the octreotide group (80+/-10mm Hg, 74+/-12, 14+/-2) and the control group (82+/-9 mm Hg, 76+/-11, 15+/-3), respectively. CONCLUSION: We demonstrated that perioperative octreotide intravenous infusion could be an adjuvant to opioid analgesia as it exerted a piritramide opioid-sparing effect. We encountered more systemic side effects such as nausea, abdominal discomfort, and diarrhea in the octreotide group than in the control group. Our findings could be beneficial to patients who cannot tolerate the adverse effects of opioids.

Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery.

BACKGROUND: The risk of preoperative anemia in patients undergoing heart surgery has not been described precisely. Specifically, the impact of low hemoglobin per se or combined with other risk factors on postoperative outcome is unknown. Thus, we determined the effects of low preoperative hemoglobin and comorbidities on postoperative adverse outcomes in patients with coronary artery bypass graft in a large comprehensive multicenter study. METHODS AND RESULTS: The Multicenter Study of Perioperative Ischemia investigated 5065 patients with coronary artery bypass graft at 70 institutions worldwide, collecting approximately 7500 data points per patient. In 4804 patients who received no preoperative transfusions, we determined the association between lowest preoperative hemoglobin levels and in-hospital cardiac and noncardiac morbidity and mortality and the impact of concomitant risk factors, assessed by EuroSCORE, on this effect. In patients with EuroSCORE < 4 (n=2054), only noncardiac outcomes were increased, whereas patients with EuroSCORE > or = 4 (n=2750) showed an increased incidence of all postoperative events, starting at hemoglobin < 11 g/dL. Low preoperative hemoglobin was an independent predictor for noncardiac (renal > cerebral; P<0.001) outcomes, whereas the increase in cardiac events was due to other factors associated with preoperative anemia. CONCLUSIONS: Anemic patients undergoing cardiac surgery have an increased risk of postoperative adverse events. Importantly, the extent of preexisting comorbidities substantially affects perioperative anemia tolerance. Therefore, preoperative risk assessment and subsequent therapeutic strategies, such as blood transfusion, should take into account both the individual level of preoperative hemoglobin and the extent of concomitant risk factors.