-
Journal of Clinical Anesthesia Jun 2022Postoperative pain management in opioid users remains challenging. The perioperative administration of ketamine might lead to favourable pain outcomes in these patients. (Meta-Analysis)
Meta-Analysis Review
STUDY OBJECTIVE
Postoperative pain management in opioid users remains challenging. The perioperative administration of ketamine might lead to favourable pain outcomes in these patients.
STUDY DESIGN
A systematic review of randomised controlled trials (RCT) with meta-analysis and assessment of the quality of evidence by GRADE was performed.
SETTING
Perioperative pain treatment.
PATIENTS
Adult opioid users undergoing surgery.
INTERVENTIONS
Perioperative administration of ketamine.
MEASUREMENTS
Primary outcomes were postoperative acute pain at rest/during movement after 24 h and number of patients with ketamine-related adverse events.
MAIN RESULTS
Nine RCTs (802 patients with at least two weeks opioid-intake) were included. There is low-quality evidence that ketamine may slightly reduce postoperative pain during movement after 24 h (mean difference: -0.79; 95% confidence interval (CI): -1.22 to -0.36). Based on a very low-quality of evidence, we are uncertain on any effect of ketamine on pain at rest after 24 h and incidences of adverse events like hallucinations and confusion within 48 h. However, perioperative ketamine reduced cumulative mean opioid consumption by 97.3 mg (95%CI: -164.8 to -29.7) after 24 h and 186.4 mg (95%CI: -347.6 to -25.2) after 48 h. The relative risks (RR) for opioid-related adverse events were significantly different for sedation within 24 h (RR: 0.54; 95%CI 0.37 to 0.78).
CONCLUSIONS
There is currently limited evidence for a reduced postoperative pain intensity using perioperative ketamine in preoperative opioid-consuming patients. However, a clinically relevant opioid-sparing effect was evident associated with a reduced risk for postoperative sedation and without increased harm. Therefore, ketamine might be a useful anti-hyperalgesic adjuvant in these patients. Nevertheless, with clinical heterogeneity being considerable, it's too premature to suggest any specific ketamine protocol. Furthermore, many questions (like ideal dosing, treatment duration and more favourable patient-related outcome measures including long-term effects) remain open and need to be addressed in future studies.
PROTOCOL REGISTRATION
Prospero CRD42020185497.
Topics: Acute Pain; Adult; Analgesics, Opioid; Humans; Hyperalgesia; Ketamine; Pain, Postoperative
PubMed: 35065394
DOI: 10.1016/j.jclinane.2022.110652 -
Pain Oct 2022Carpal tunnel syndrome (CTS) is the most common nerve compression in the arm. A mix of peripheral and central contributions on quantitative sensory testing (QST) has... (Meta-Analysis)
Meta-Analysis
Carpal tunnel syndrome (CTS) is the most common nerve compression in the arm. A mix of peripheral and central contributions on quantitative sensory testing (QST) has been reported in the literature. Thus, this systematic review or meta-analysis aimed to identify the dominant sensory phenotype and draw conclusive evidence about the presence of central sensitization (CS) in CTS. Based on an a priori published protocol and using PRISMA guidelines, 7 databases were searched (Embase, Web of Science, Scopus, PubMed, SAGE, EBSCOhost, and ProQuest). Eligible studies compared the QST findings of individuals with subacute and chronic CTS with those of healthy controls through thermal, mechanical, and vibration detection thresholds; thermal, pressure, and mechanical pain thresholds; mechanical pain sensitivity; presence of allodynia; wind-up ratio; and conditioned pain modulation. Thirty-seven studies were included in the qualitative analysis. Results showed a significant loss of all detection thresholds of hand median nerve territories and hand extramedian areas (little finger and hand dorsum) in CTS ( P < 0.05) but no significant difference ( P > 0.05) in wind-up ratio, cold, heat, or mechanical pain thresholds of the median nerve territories. Furthermore, there was a significant increase in mechanical pain sensitivity in median nerve territories and remotely in the forearm ( P < 0.05) and a significant gain in pressure and heat pain thresholds in the carpal area ( P < 0.05). Conditioned pain modulation was impaired in CTS. Hypoesthesia and increased thermal and mechanical pain ratings are the dominant sensory phenotype with inconclusive evidence about CS in CTS due to the heterogenous results of thermal and mechanical pain thresholds.
Topics: Carpal Tunnel Syndrome; Humans; Median Nerve; Pain; Pain Measurement; Pain Threshold
PubMed: 35050958
DOI: 10.1097/j.pain.0000000000002566 -
The Korean Journal of Pain Jan 2022Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present...
BACKGROUND
Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management.
METHODS
Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI).
RESULTS
Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia.
CONCLUSIONS
A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.
PubMed: 34966011
DOI: 10.3344/kjp.2022.35.1.43 -
Journal of Pain Research 2021Acetaminophen (APAP) in humans has robust effects with a high therapeutic index in altering postoperative and inflammatory pain states in clinical and experimental pain... (Review)
Review
Acetaminophen (APAP) in humans has robust effects with a high therapeutic index in altering postoperative and inflammatory pain states in clinical and experimental pain paradigms with no known abuse potential. This review considers the literature reflecting the preclinical actions of acetaminophen in a variety of pain models. Significant observations arising from this review are as follows: 1) acetaminophen has little effect upon acute nociceptive thresholds; 2) acetaminophen robustly reduces facilitated states as generated by mechanical and thermal hyperalgesic end points in mouse and rat models of carrageenan and complete Freund's adjuvant evoked inflammation; 3) an antihyperalgesic effect is observed in models of facilitated processing with minimal inflammation (eg, phase II intraplantar formalin); and 4) potent anti-hyperpathic effects on the thermal hyperalgesia, mechanical and cold allodynia, allodynic thresholds in rat and mouse models of polyneuropathy and mononeuropathies and bone cancer pain. These results reflect a surprisingly robust drug effect upon a variety of facilitated states that clearly translate into a wide range of efficacy in preclinical models and to important end points in human therapy. The specific systems upon which acetaminophen may act based on targeted delivery suggest both a spinal and a supraspinal action. Review of current targets for this molecule excludes a role of cyclooxygenase inhibitor but includes effects that may be mediated through metabolites acting on the TRPV1 channel, or by effect upon cannabinoid and serotonin signaling. These findings suggest that the mode of action of acetaminophen, a drug with a long therapeutic history of utilization, has surprisingly robust effects on a variety of pain states in clinical patients and in preclinical models with a good therapeutic index, but in spite of its extensive use, its mechanisms of action are yet poorly understood.
PubMed: 34795520
DOI: 10.2147/JPR.S308028 -
Frontiers in Cellular and Infection... 2021In recent years, increasing studies have been conducted on the mechanism of gut microbiota in neuropsychiatric diseases and non-neuropsychiatric diseases. The academic... (Review)
Review
In recent years, increasing studies have been conducted on the mechanism of gut microbiota in neuropsychiatric diseases and non-neuropsychiatric diseases. The academic community has also recognized the existence of the microbiota-gut-brain axis. Chronic pain has always been an urgent difficulty for human beings, which often causes anxiety, depression, and other mental symptoms, seriously affecting people's quality of life. Hyperalgesia is one of the main adverse reactions of chronic pain. The mechanism of gut microbiota in hyperalgesia has been extensively studied, providing a new target for pain treatment. Enterochromaffin cells, as the chief sentinel for sensing gut microbiota and its metabolites, can play an important role in the interaction between the gut microbiota and hyperalgesia through paracrine or neural pathways. Therefore, this systematic review describes the role of gut microbiota in the pathological mechanism of hyperalgesia, learns about the role of enterochromaffin cell receptors and secretions in hyperalgesia, and provides a new strategy for pain treatment by targeting enterochromaffin cells through restoring disturbed gut microbiota or supplementing probiotics.
Topics: Brain; Enterochromaffin Cells; Gastrointestinal Microbiome; Humans; Hyperalgesia; Probiotics; Quality of Life
PubMed: 34722345
DOI: 10.3389/fcimb.2021.760076 -
The Clinical Journal of Pain Oct 2021Opioid-induced hyperalgesia (OIH) remains an issue in patients with chronic pain. Multiple cases of OIH in patients with chronic pain exposed to opioids have been...
INTRODUCTION
Opioid-induced hyperalgesia (OIH) remains an issue in patients with chronic pain. Multiple cases of OIH in patients with chronic pain exposed to opioids have been reported worldwide. The objective of this systematic review was to summarize the evidence of OIH from clinical reports.
METHODS
We searched the PubMed, Cochrane, EMBASE, and LILACS databases for case reports and case series of OIH published up to December 2020, with the aim to summarize the evidence for OIH in patients with chronic pain from clinical reports and to discuss issues relevant to the clinical diagnosis and management of OIH.
RESULTS
We retrieved and reviewed 41 articles describing 72 cases. Clinical features of OIH were observed in patients of both sexes, all ages, and with various types of pain treated with different classes of opioids. OIH was reported at all doses, but most published studies reported a pattern of OIH following treatment with very high daily doses of opioids (median oral morphine equivalent dose of 850 mg). OIH was diagnosed clinically in all cases. Three different strategies for OIH management were described: opioid rotation, opioid cessation, and the use of adjuvant pharmacotherapies. All had statistically similar success rates for OIH treatment: 72%, 57%, and 79%, respectively. The decrease in pain was achieved rapidly (mean: 8 d; range: 1 to 28 d). Adjuvant therapies resulted in the largest decrease in dose. Ketamine and dexmedetomidine were the most widely used adjuvant drugs.
CONCLUSION
The key finding is that clinical symptoms of OIH can be resolved when this condition is diagnosed and managed.
Topics: Analgesics, Opioid; Chronic Pain; Female; Humans; Hyperalgesia; Male; Morphine; Pain Management
PubMed: 34699405
DOI: 10.1097/AJP.0000000000000994 -
Pain Medicine (Malden, Mass.) May 2022Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal... (Meta-Analysis)
Meta-Analysis
Pain-Related Post-Exertional Malaise in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A Systematic Review and Three-Level Meta-Analysis.
OBJECTIVE
Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon in which symptom severity is worsened for 24 hours or longer after physical stress, but the pain-related component of PEM is not well characterized.
DESIGN
Systematic review and meta-analysis.
METHODS
Case-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges' d effect sizes were aggregated with random-effects models, and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects with three-level modeling.
RESULTS
Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small to moderate effect indicating higher post-exercise pain in patients than in controls (Hedges' d = 0.42; 95% confidence interval [CI]: 0.16-0.67). The mean effect was significantly moderated by pain measurement time point (b = -0.19, z = -2.57, P = 0.01), such that studies measuring pain 8-72 hours after exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than did those measuring pain 0-2 hours after exercise (d = 0.32, 95% CI = 0.10-0.53).
CONCLUSIONS
People with ME/CFS and FM experience small to moderate increases in pain severity after exercise, which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.
Topics: Adult; Exercise; Exercise Test; Fatigue Syndrome, Chronic; Fibromyalgia; Humans; Pain
PubMed: 34668532
DOI: 10.1093/pm/pnab308 -
European Journal of Pain (London,... Jan 2022After whiplash injury, some patients develop chronic whiplash-associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge...
BACKGROUND AND OBJECTIVE
After whiplash injury, some patients develop chronic whiplash-associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post-injury phases. Therefore, studies were searched that examined temporal changes in pain processing, measured by Quantitative Sensory Testing (QST).
DATABASES AND DATA TREATMENT
This systematic review searched three electronic databases (Medline, Web of Science and Embase) for articles meeting the eligibility requirements. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale.
RESULTS
The 12 included studies presented moderate to good methodological quality. These studies showed altered pain processing within the first month after injury and normalization within 3 months in 59%-78% of the patients. After 3 months, recovery stagnates during the following years. Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non-recovered patients.
CONCLUSIONS
Differences in pain processing between recovering and non-recovering patients can be observed already in the acute phase. Early screening for signs of altered pain processing can identify patients with high risk for chronification. These insights in temporal changes show the importance of rehabilitation in the acute phase. Future research should target to develop a standardized (bed-site) QST protocol and collect normative data which could, in relation with self-reported pain parameters, allow clinicians to identify the risk for chronification.
SIGNIFICANCE
Altered pain processing is present soon after whiplash injury, but usually recovers within 3 months. Non-recovering patients show little to no improvements in the following years. Differences between recovering and non-recovering patients can be observed by Quantitative Sensory Testing already in the acute phase. Therefore, it is considered a feasible and effective tool that can contribute to the identification of high-risk patients and the prevention of chronification.
Topics: Chronic Disease; Humans; Hyperalgesia; Pain; Pain Measurement; Whiplash Injuries
PubMed: 34464486
DOI: 10.1002/ejp.1858 -
Scandinavian Journal of Pain Apr 2021Experimental pain is a commonly used method to draw conclusions about the motor response to clinical musculoskeletal pain. A systematic review was performed to determine... (Review)
Review
OBJECTIVES
Experimental pain is a commonly used method to draw conclusions about the motor response to clinical musculoskeletal pain. A systematic review was performed to determine if current models of acute experimental pain validly replicate the clinical experience of appendicular musculoskeletal pain with respect to the distribution and quality of pain and the pain response to provocation testing.
METHODS
A structured search of Medline, Scopus and Embase databases was conducted from database inception to August 2020 using the following key terms: "experimental muscle pain" OR "experimental pain" OR "pain induced" OR "induced pain" OR "muscle hyperalgesia" OR ("Pain model" AND "muscle"). Studies in English were included if investigators induced experimental musculoskeletal pain into a limb (including the sacroiliac joint) in humans, and if they measured and reported the distribution of pain, quality of pain or response to a provocation manoeuvre performed passively or actively. Studies were excluded if they involved prolonged or delayed experimental pain, if temporomandibular, orofacial, lumbar, thoracic or cervical spine pain were investigated, if a full text of the study was not available or if they were systematic reviews. Two investigators independently screened each title and abstract and each full text paper to determine inclusion in the review. Disagreements were resolved by consensus with a third investigator.
RESULTS
Data from 57 experimental pain studies were included in this review. Forty-six of these studies reported pain distribution, 41 reported pain quality and six detailed the pain response to provocation testing. Hypertonic saline injection was the most common mechanism used to induce pain with 43 studies employing this method. The next most common methods were capsaicin injection (5 studies) and electrical stimulation, injection of acidic solution and ischaemia with three studies each. The distribution of experimental pain was similar to the area of pain reported in clinical appendicular musculoskeletal conditions. The quality of appendicular musculoskeletal pain was not replicated with the affective component of the McGill Pain Questionnaire consistently lower than that typically reported by musculoskeletal pain patients. The response to provocation testing was rarely investigated following experimental pain induction. Based on the limited available data, the increase in pain experienced in clinical populations during provocative maneuvers was not consistently replicated.
CONCLUSIONS
Current acute experimental pain models replicate the distribution but not the quality of chronic clinical appendicular musculoskeletal pain. Limited evidence also indicates that experimentally induced acute pain does not consistently increase with tests known to provoke pain in patients with appendicular musculoskeletal pain. The results of this review question the validity of conclusions drawn from acute experimental pain studies regarding changes in muscle behaviour in response to pain in the clinical setting.
Topics: Abdominal Pain; Acute Pain; Chronic Pain; Humans; Musculoskeletal Pain; Pain Measurement
PubMed: 34387953
DOI: 10.1515/sjpain-2020-0076 -
PloS One 2021The contact burn injury model is an experimental contact thermode-based physiological pain model primarily applied in research of drug efficacy in humans. The employment...
The contact burn injury model is an experimental contact thermode-based physiological pain model primarily applied in research of drug efficacy in humans. The employment of the contact burn injury model across studies has been inconsistent regarding essential methodological variables, challenging the validity of the model. This systematic review analyzes methodologies, outcomes, and research applications of the contact burn injury model. Based on these results, we propose an improved contact burn injury testing paradigm. A literature search was conducted (15-JUL-2020) using PubMed, EMBASE, Web of Science, and Google Scholar. Sixty-four studies were included. The contact burn injury model induced consistent levels of primary and secondary hyperalgesia. However, the analyses revealed variations in the methodology of the contact burn injury heating paradigm and the post-burn application of test stimuli. The contact burn injury model had limited testing sensitivity in demonstrating analgesic efficacy. There was a weak correlation between experimental and clinical pain intensity variables. The data analysis was limited by the methodological heterogenicity of the different studies and a high risk of bias across the studies. In conclusion, although the contact burn injury model provides robust hyperalgesia, it has limited efficacy in testing analgesic drug response. Recommendations for future use of the model are being provided, but further research is needed to improve the sensitivity of the contact burn injury method. The protocol for this review has been published in PROSPERO (ID: CRD42019133734).
Topics: Analgesics; Burns; Female; Humans; Hyperalgesia; Male; Models, Biological; Pain; Pain Measurement
PubMed: 34329326
DOI: 10.1371/journal.pone.0254790