British Journal of Pain最新文献

Background: Preliminary research indicates that psychedelics may hold promise as analgesic agents. This study investigated the potential analgesic effects of lysergic acid diethylamide (LSD) microdosing on pain tolerance and subjective pain perception in healthy participants.

Methods: Utilizing a randomised, placebo-controlled design, participants received 15 μg of LSD or placebo over four administrations. Pain tolerance was assessed using the Cold Pressor Task (CPT), along with subjective ratings of painfulness, unpleasantness, and stress.

Results: No analgesic effects of LSD were found on any of these measures in the whole sample. LSD increased blood pressure and subjective ratings of drug experience on administration days. Blood pressure was positively correlated to pain tolerance in the LSD group, whereas subjective drug experience was not. To explore whether the absence of analgesic effects of LSD could be explained by ceiling effects observed in CPT performance, post-hoc analyses were conducted in a smaller subsample of individuals that did not show ceiling effects at baseline. This post-hoc analysis suggested that LSD increased pain tolerance and reduced unpleasantness, but only after the first dose.

Conclusions: Overall, the present study provided no evidence for analgesic effects of 15 µg LSD. Post-hoc analyses only revealed a marginal analgesic effect of LSD in a subsample of participants. The dose used in this study may be below the threshold dose that is needed to produce a solid and consistent analgesic effect. Future research with larger, appropriately selected samples and higher doses is recommended to further elucidate LSD's analgesic effects and its application in clinical settings.

Introduction: Sensory discrimination training has demonstrated improvements in two-point discrimination and pain reduction in people with chronic pain. We tested the feasibility and acceptability of a novel Sensory Training System (STS) device in the homes of people with Type 1 Complex Regional Pain Syndrome (CRPS).

Methods: Participants meeting CRPS diagnostic criteria were invited to use the STS for a minimum of 30 minutes per day for 30 days. Device usage data were captured by the STS. Assessments at baseline and after 30 days were: two-point discrimination ability, pain intensity and interference, sensitivity and emotions towards CRPS limb. Qualitative interviews were conducted at the end of the study to capture participants' feedback on the device.

Results: A total of 10 participants (female n = 7) completed the study. Participants' mean age was 56.4 years (range: 24-78 years), and mean disease duration was 9.37 years (range: 4.25-26.5). Eight had lower limb CRPS. The mean STS device use was 27.3 ± 3.4 days and mean daily usage of training games was 00:27:11 ± 00:07:52 (hh:mm:ss). No patterns or trends were evident between device usage and outcome data.

Conclusion: This feasibility study of a home-based STS for people with CRPS revealed key areas for improvement in the device's hardware and software and outlined the challenges of development and testing during the COVID-19 pandemic, while also capturing valuable usability insights from participant feedback. Key recommendations include early and ongoing collaboration with users, securing sufficient funding, ensuring correct device setup by participants, conducting interim analysis, and using online tools to enhance participant experience and data collection.

Study registration: The study was registered with ISRCTN registry on 28^th May 2021 (https://doi.org/10.1186/ISRCTN89099843).

Background and objective: Painful diabetic neuropathy (PDN) is a common complication of diabetes, characterized by significant pain and functional impairment. Gabapentin and duloxetine are standard treatments. This study compared their efficacy in alleviating pain, improving clinical global impression of change (CGIC), reducing sleep interference, enhancing response rates, and assessing safety.

Methods: A systematic review and meta-analysis was conducted following PRISMA guidelines. A search of Embase, Medline, ScienceDirect, Scopus, Web of Science, and Cochrane databases through May 2024 identified randomized controlled trials comparing gabapentin and duloxetine for PDN. Risk of bias was assessed using the Cochrane RoB2 tool. Data on pain, CGIC, sleep interference, responder rates, and adverse events were analyzed using a random-effects model, with results presented as standardized mean differences and risk ratios with 95% confidence intervals.

Results: Six RCTs with 526 patients (44% female) were included. There was no significant difference between duloxetine and gabapentin in relieving pain (SMD = -0.16, 95% CI [-0.36, 0.03], p = .10, I² = 66%). No significant differences were observed in the overall effect of CGIC (MD = 0.01, 95% CI [-0.07, 0.09], p = .79, I² = 0%), or sleep interference (MD = -0.07, 95% CI [-0.36, 0.23], p = .67, I² = 39%); However, duloxetine showed superiority at week 1 for CGIC (MD = 0.56, 95% CI [0.18, 0.94], p = .003), and week 8 for sleep interference (MD = -0.40, 95% CI [-0.79, -0.01], p = .04, I² = 0%), while gabapentin was superior at week 1 in sleep interference (MD = 0.75, 95% CI [0.11, 1.39], p = .02). No significant differences were observed in responder rates or adverse events.

Conclusion: Gabapentin and duloxetine are effective for PDN, with distinct advantage at different time points. Personalized treatment is recommended, and future research should assess long-term efficacy in diverse populations.

Objectives: A significant driver of low back pain (LBP) is adaptations to endogenous pain modulation (EPM). Exercise modulates pain through various mechanisms, however, there is a lack of information on its relation to EPM. The objective of this study was to evaluate the feasibility of a protocol investigating if changes in EPM occurs after exercise therapy.

Methods: Participants were recruited from an ongoing randomized controlled trial comparing graded activity to motor control exercises. Participants attended 2 in person sessions pre and post intervention to assess pain pressure threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM) and exercise induced hypoalgesia (EIH). Feasibility outcomes included attrition, recruitment rate, exercise adherence, protocol burden and consistency. In total, 36 (53%) eligible participants enrolled and completed baseline assessments.

Results: A-priori thresholds for feasibility were met for attrition 32/36 (89%), recruitment rate (53% of eligible participant enrolled and 36 recruited in 6 months), exercise adherence (93.8%) and satisfaction with assessment protocols (bothersome 88.9%, future participation 97.2%), apart from discomfort with assessment (58.3%). Participants reported that the CPM caused the most discomfort. There was a trend for an increase in low back PPT, no change in TS, and a decrease in CPM and thumbnail PPT at follow up. The results demonstrated that the protocol is feasible for all pre-specified outcomes.

Discussion: This article presents a protocol for EPM using PPT, TS, CPM and EIH that is feasible in a clinical trial for LBP. A future study is needed to further investigate EPM changes after exercise therapy in this population.

Background: Knee osteoarthritis (OA) is the most common form of OA. Patients with mild-to-moderate OA, who do not respond to conservative treatment or yet warrant joint replacement, represent a significant clinical challenge. Genicular Arterial Embolisation (GAE) is a promising interventional radiological technique for OA. However, data highlight a consistent subset of patients that do not respond to GAE, despite a successful procedure. Pain Catastrophising (PC) represents a set of cognitive/affective biases to pain, linked to maladaptations in the descending pain modulatory system and has been frequently identified as a predictor of clinical outcomes. Purpose: This study aimed to investigate whether baseline pain catastrophising is associated with treatment outcomes following GAE, and to explore its neural correlates using resting-state functional magnetic resonance imaging (rs-fMRI). Research Design: A prospective, longitudinal cohort design was employed for this study. Study Sample: Thirty patients with mild-to-moderate knee OA scheduled for GAE completed a presurgical assessment including psychometric profiling and quantitative sensory testing. A neuroimaging subset of 17 patients, who met MRI safety criteria, also completed rs-fMRI. Data Collection: Participants completed outcome assessments at 6 weeks, 3 months, and 12 months post-GAE. Pain Catastrophising Scale (PCS) scores were analysed in relation to treatment outcomes and to whole-brain voxel-wise functional connectivity using the dorsolateral prefrontal cortex (DLPFC) as a seed region. PCS scores were included as regressors in rs-fMRI analyses. Results: Pain Catastrophising was associated with a myriad of psychological/lifestyle baseline variables, such as depression, anxiety and poor sleep. Surprisingly, high pain catastrophisers demonstrated the best improvements, with PC scores predicting higher reductions in pain at 6-weeks (R² = .18, p = .024), 3-months (R² = .37, p < .001) and 1-year (R² = .18, p = .027). Resting-state analyses revealed that catastrophising was associated with higher connectivity between the DLPFC and areas of the brain associated with pain processing, suggesting more frequent engagement of top-down modulatory processes. Conclusions: These results highlight that, interestingly, patients who catastrophise may benefit most from GAE. Potential explanations for this are discussed within. Overall, this data indicates GAE is an effective treatment for knee OA, and may be valuable at managing pain for high catastrophisers, who often fare worse in more invasive surgical procedures.

Pain is cited as a fundamental rationale behind the campaign for 'assisted dying' (assisted suicide and euthanasia). However, current legislative proposals for England and Wales before the Westminster Parliament are silent on pain and on suffering. For patients to have real choice, they must be able to access the care they need, not feel coerced into viewing an early death as their only option. Yet current palliative care provision is dependent on voluntary donations, with severe deficits in some areas that urgently need to be addressed.

Objective: In this study, a meta-analysis was conducted to characterize the therapeutic benefits of repetitive transcranial magnetic stimulation (rTMS) on musculoskeletal (MSK) pain and potential factors affecting the effect.

Methods: A comprehensive search was performed in PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov for randomized and sham-controlled trials published from inception to 13 March 2024. We conducted this meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Based on the heterogeneity among studies, fixed effects or random-effects model was used for the effective analysis of rTMS on pain, quality of life, and depression.

Results: A total of 23 eligible randomized controlled trials (RCTs) comprising 1158 patients were included in our systematic search. The analysis showed effect sizes of -0.94 (95% CI: -1.30 to -0.59), indicating that real rTMS was better than sham stimulation in reducing pain (p < 0.01). Also, rTMS reduced depression scores and improved follow-up effects and the quality of life of MSK pain patients. In the subgroup analysis, stimulation frequency, intensity, and session frequency were important factors affecting the therapeutic effect.

Conclusions: Our review demonstrated that rTMS had the potential to relieve pain and depression, enhance the quality of life for patients with MSK pain. Stimulation frequency, intensity, and session frequency were important factors affecting the therapeutic effect.

Background: Opioids can heighten sensitivity to noxious stimuli, leading to opioid-induced hyperalgesia (OIH). Despite the frequent use of high opioid doses in ICU settings, the presence of OIH following ICU stays remains undocumented.

Methods: This prospective observational study aimed to assess OIH presence and its clinical implications in post-ICU patients. Adults with confirmed Sars-CoV-2 infection hospitalized in the ICU for over 48 h were included, with opioid dosage recorded. At ICU discharge, 11 quantitative sensory tests (QSTs) were conducted at two non-painful sites, and pain presence, intensity, and characteristics were assessed at discharge and 4 months later.

Results: Analysis of 41 patients (20 opioid-treated, 21 controls) revealed significantly higher hyperalgesia levels in the opioid-treated group across six tests at both sites, including cold pain thresholds, heat and cold tolerance thresholds, duration of tolerance to a 47°C stimulus, and thermal and mechanical temporal summation.

Conclusions: Our findings underscore the importance of QST in early OIH detection, identifying thermal tolerance thresholds and thermal/mechanical temporal summation tests as sensitive indicators. Subclinical hyperalgesia in ICU patients on opioids heightens susceptibility to chronic pain development, emphasizing the need for vigilant opioid monitoring and adjustment in ICU care.

Cancer pain is one of the most severe components of the symptom burden among cancer patients, especially those with advanced or metastatic disease. Palliative interventions are necessary to alleviate cancer pain and reduce opioid-related side effects, thereby minimizing patient suffering. Radiosurgery has been effectively used to target the medial thalamus and the hypophysis for the treatment of chronic pain syndromes. These two areas are critical for pain modulation and control, and their precise targeting with radiosurgery and its non-invasive nature can provide relief for patients suffering from cancer-related intractable pain. Our previous work with single target irradiation of the hypophysis revealed promising pain relief in terminal cancer patients, albeit more suited for hormone-mediated tumours or bone-derived pain rather than complex mixed pain syndromes. Given that, we previously introduced the concept of triple-target irradiation (hypophysis + both thalami) in a small report of terminally ill cancer patients. Here, we report a larger case series of terminally ill patients (n = 8) with complex cancer pain treated with a triple-target approach, with radiation doses generally considered low or non-ablative (90 Gy), in contrast to the usual single-target, ablative approach comprising higher doses. We noted a substantial decrease in VAS scores and the medications needed to manage pain across all patients, experiencing minimal to no side effects. Our findings indicate that a minimally invasive triple-target method, utilising low radiation doses, effectively alleviates pain, lowers medication dependency, and enhances the quality of life with few side effects. Furthermore, additional research is essential to optimise pain relief and ensure long-term effectiveness.

Background: Perioperative opioid stewardship programs are increasingly being introduced to guide responsible use around the time of surgery to reduce opioid-related harm to patients. However, patient experiences of perioperative opioid stewardship programs are underexplored.

Methods: We designed a mixed methods study to explore patients' experiences of perioperative opioid stewardship in the post-operative period following spine surgery. We performed evaluative action research, combining quality improvement and ethnographic methodologies. Our quantitative methods were retrospective medical record review and targeted survey research. Our qualitative methods were online focus groups. The quantitative data were analysed using descriptive statistics, chi-square, and rank sum testing. The focus group data underwent inductive thematic analysis.

Results: Our spine surgery cohort for the four-month study period included 101 patients. The median total discharge opioid dispensed was 75 mg [interquartile range 75-150 mg], with 30% of patients prescribed modified release opioids on discharge. A subset of patients (N = 14) participated in the online focus groups. The key themes that emerged from these sessions were (1) Supportive care delivery and rescue mechanisms were universally important to patient participants, providing great reassurance during their recovery; (2) Participants commonly believed opioid analgesia had an important role in recovery following spine surgery. Some patients were keen to dispose of surplus opioids whilst others intended to retain them; (3) Opioid analgesia access was variable, but established community prescriber relationships were important for post-discharge opioid re-prescription, and (4) The key future improvement suggestions included routine post-discharge contact and enhanced communication options back to the hospital if needed.

Discussion and conclusions: Our mixed methods approach provided rich insights into the pain and opioid analgesia experiences of patients following spine surgery. These insights are useful when seeking to optimise perioperative opioid stewardship programs including better meeting the needs of patient consumers. Limitations included potential response and selection bias for the online focus groups towards younger, higher socioeconomic status patients.