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Pain Physician Jan 2021Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia, prickling, pain, or allodynia.
OBJECTIVES
To evaluate the relative efficacy and safety of the interventions used in the DPN pain management and rank their order.
STUDY DESIGN
A systematic review and Bayesian network meta-analysis (NMA).
METHODS
Randomized, controlled trials were identified through a comprehensive, systematic literature exploration, primarily utilizing the PubMed, EMBASE, Ovid, and Cochrane Library databases. The efficacy and safety outcomes consist of the proportion of patients reporting either 30% or 50% pain reduction and overall withdrawal or withdrawal due to adverse drug events, respectively. Effect estimates from Bayesian NMA were presented as odds ratio (OR) with 95% credible intervals (CrI). Heterogeneity and convergence were assessed by using I2 and deviation information criteria. The risk of bias was evaluated by using Pedro Scale.
RESULTS
A total of 3,246 potentially relevant trials were identified and screened, finally 43 trials consisting of 7,877 randomized patients met the inclusion criteria. Statistically significant treatment difference for 50% pain reduction was reported for duloxetine vs. placebo (OR: 2.50; CrI: 1.62-3.91), mirogabalin vs. placebo (OR: 3.25; CrI: 1.16-9.35), pregabalin vs. placebo (OR: 2.33; CrI: 1.69-3.27), duloxetine vs. carbamazepine (OR: 3.37; CrI: 1.07-10.90), mirogabalin vs. carbamazepine (OR: 4.39; CrI: 1.01-19.63), mirogabalin vs. lamotrigine (OR: 4.05: CrI: 1.07-15.77), pregabalin vs. lamotrigine (OR: 2.90, CrI: 1.19-7.22) and pregabalin vs. nortriptyline (OR: 4.10, CrI: 1.13-5.28). Nortriptyline reported the highest possibility of achieving 30% and 50% pain reduction. Sodium valproate and benztropine reported the highest probability of total withdrawals and withdrawals due to adverse drug events, respectively.
LIMITATION
The different follow-up time of the included studies can result in the variation of intended results.
CONCLUSION
Nortriptyline reported the advantage relative to other drugs in achieving 30% and 50% pain reduction from the baseline. Gabapentin reported a significance of 50% pain reduction relative to placebo.
Topics: Bayes Theorem; Diabetic Neuropathies; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33400429
DOI: No ID Found -
Journal of Athletic Training Aug 2021Patellofemoral pain (PFP) has high recurrence rates and minimal long-term treatment success. Central sensitization refers to dysfunctional pain modulation that occurs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patellofemoral pain (PFP) has high recurrence rates and minimal long-term treatment success. Central sensitization refers to dysfunctional pain modulation that occurs when nociceptive neurons become hyperresponsive. Researchers in this area of PFP have been increasingly productive in the past decade.
OBJECTIVE
To determine whether evidence supports manifestations of central sensitization in individuals with PFP.
DATA SOURCES
We searched MeSH terms for quantitative sensory testing (QST) pressure pain thresholds (PPTs), conditioned pain modulation (CPM), temporal summation, sensitization, hyperalgesia, and anterior knee pain or PFP in PubMed, SPORTDiscus, CINAHL, Academic Search Complete, and EBSCOhost.
STUDY SELECTION
Peer-reviewed studies that were written in English and published between 2005 and 2020 and investigated QST or pain mapping in a sample with PFP were included in this review.
DATA EXTRACTION
The initial search yielded 140 articles. After duplicates were removed, 78 abstracts were reviewed. The full text of 21 studies was examined, and we included 15 studies in our evaluation: 6 in the meta-analysis, 4 in the systematic review, and 5 in both the meta-analysis and systematic review.
DATA SYNTHESIS
A random-effects meta-analysis was conducted for 4 QST variables (local PPTs, remote PPTs, CPM, temporal summation). Strong evidence supported lower local and remote PPTs, impaired CPM, and facilitated temporal summation in individuals with PFP compared with pain-free individuals. Evidence for heat and cold pain thresholds was conflicting. Pain mapping demonstrated expanding pain patterns associated with long duration of PFP symptoms.
CONCLUSIONS
Signs of central sensitization were present in individuals with PFP, indicating altered pain modulation. The etiologic and treatment models of PFP should reflect the current body of evidence regarding central sensitization. Signs of central sensitization should be monitored clinically, and treatments with central effects should be considered as part of a multimodal plan of care.
Topics: Central Nervous System Sensitization; Humans; Pain; Pain Threshold; Patellofemoral Pain Syndrome; Quality of Life
PubMed: 33238005
DOI: 10.4085/1062-6050-0190.20 -
Cephalalgia : An International Journal... Mar 2021Despite increasing evidence differentiating episodic and chronic migraine, little work has determined how currently utilized animal models of migraine best represent...
BACKGROUND
Despite increasing evidence differentiating episodic and chronic migraine, little work has determined how currently utilized animal models of migraine best represent each distinct disease state.
AIM
In this review, we seek to characterize accepted preclinical models of migraine-like headache by their ability to recapitulate the clinical allodynic features of either episodic or chronic migraine.
METHODS
From a search of the Pu bMed database for "animal models of migraine", "headache models" and "preclinical migraine", we identified approximately 80 recent (within the past 20 years) publications that utilized one of 10 different models for migraine research. Models reviewed fit into one of the following categories: Dural KCl application, direct electrical stimulation, nitroglycerin administration, inflammatory soup injection, CGRP injection, medication overuse, monogenic animals, post-traumatic headache, specific channel activation, and hormone manipulation. Recapitulation of clinical features including cephalic and extracephalic hypersensitivity were evaluated for each and compared.
DISCUSSION
Episodic migraineurs comprise over half of the migraine population, yet the vast majority of current animal models of migraine appear to best represent chronic migraine states. While some of these models can be modified to reflect episodic migraine, there remains a need for non-invasive, validated models of episodic migraine to enhance the clinical translation of migraine research.
Topics: Animals; Disease Models, Animal; Headache; Hyperalgesia; Migraine Disorders
PubMed: 33131303
DOI: 10.1177/0333102420966984 -
Frontiers in Physiology 2020Placebo/nocebo effects involve the autonomic nervous system, including cardiac activity, but studies have reported inconsistent findings on how cardiac activity is...
Placebo/nocebo effects involve the autonomic nervous system, including cardiac activity, but studies have reported inconsistent findings on how cardiac activity is modulated following a placebo/nocebo effect. However, no systematic review has been conducted to provide a clear picture of cardiac placebo responses. The main goal of the present study is to review the effects of placebo analgesia and nocebo hyperalgesia on cardiac activity as measured by blood pressure, heart rate, and heart rate variability. Using several Boolean keyword combinations, the PubMed, EMBASE, PsycINFO, Cochrane Review Library, and ISI Web of Knowledge databases were searched until January 5, 2020, to find studies that analyzed blood pressure, heart rate, or heart rate variability indexes following a placebo analgesic/nocebo hyperalgesic effect. Nineteen studies were found, with some reporting more than one index of cardiac activity; eight studies were on blood pressure, 14 studies on heart rate, and six on heart rate variability. No reliable association between placebo/nocebo effects and blood pressure or heart rate was found. However, placebo effects reduced, and nocebo effects increased low-frequency heart rate variability, and heart rate variability significantly predicted placebo effects in two studies. Placebo/nocebo effects can have reliable effects on heart rate variability, but not on heart rate and blood pressure.
PubMed: 33101048
DOI: 10.3389/fphys.2020.549807 -
The Journal of Pain 2020This systematic review and meta-analysis examined the evidence for altered central pain processing in people with nontraumatic neck pain and the relationship among... (Comparative Study)
Comparative Study Meta-Analysis
This systematic review and meta-analysis examined the evidence for altered central pain processing in people with nontraumatic neck pain and the relationship among central pain processing, demographics, and pain-related characteristics. Case-control studies reporting measures of altered central pain processing using quantitative sensory testing were reviewed. Standardized mean differences (SMDs) and 95% confidence intervals between people with nontraumatic neck pain and controls were calculated. Meta-analysis was performed using random-effects models when appropriate. Associations between SMDs with demographics and pain-related characteristics were explored on a study level using metaregression. Twenty-six studies were eligible with 25 included for meta-analysis. Meta-analysis demonstrated mechanical hyperalgesia at remote nonpainful sites in the full sample (sample size [n] = 1305, SMD = -0.68) and in the subgroup with moderate/severe disability (n = 165, SMD = -0.86; moderate-quality evidence). Metaregression indicated that remote mechanical hyperalgesia was negatively associated with age (R = 25.4%, P = 0.031). Very low- to low-quality evidence of remote cold and heat hyperalgesia and dysfunctional conditioned pain modulation were identified. This review suggests that altered central pain processing is present in people with nontraumatic neck pain and may be associated with disability levels and age. PERSPECTIVE: This review found moderate-quality evidence of mechanical hyperalgesia at remote nonpainful sites in patients with nontraumatic neck pain compared with controls, indicating altered central pain processing. However, more studies are needed to confirm findings from dynamic quantitative sensory testing.
Topics: Case-Control Studies; Central Nervous System Sensitization; Humans; Neck Pain; Observational Studies as Topic; Pain Measurement; Pain Threshold
PubMed: 32574788
DOI: 10.1016/j.jpain.2020.02.007 -
Frontiers in Neuroscience 2019Opioid long-term therapy can produce tolerance, opioid-induced hyperalgesia (OIH), and it induces dysfunction in pain descending pain inhibitory system (DPIS). This...
Transcranial Direct Current Stimulation to Improve the Dysfunction of Descending Pain Modulatory System Related to Opioids in Chronic Non-cancer Pain: An Integrative Review of Neurobiology and Meta-Analysis.
Opioid long-term therapy can produce tolerance, opioid-induced hyperalgesia (OIH), and it induces dysfunction in pain descending pain inhibitory system (DPIS). This integrative review with meta-analysis aimed: (i) To discuss the potential mechanisms involved in analgesic tolerance and opioid-induced hyperalgesia (OIH). (ii) To examine how the opioid can affect the function of DPIS. (ii) To show evidence about the tDCS as an approach to treat acute and chronic pain. (iii) To discuss the effect of tDCS on DPIS and how it can counter-regulate the OIH. (iv) To draw perspectives for the future about the tDCS effects as an approach to improve the dysfunction in the DPIS in chronic non-cancer pain. Relevant published randomized clinical trials (RCT) comparing active (irrespective of the stimulation protocol) to sham tDCS for treating chronic non-cancer pain were identified, and risk of bias was assessed. We searched trials in PubMed, EMBASE and Cochrane trials databases. tDCS protocols accepted were application in areas of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), or occipital area. Fifty-nine studies were fully reviewed, and 24 with moderate to the high-quality methodology were included. tDCS improved chronic pain with a moderate effect size [pooled standardized mean difference; -0.66; 95% confidence interval (CI) -0.91 to -0.41]. On average, active protocols led to 27.26% less pain at the end of treatment compared to sham [95% CI; 15.89-32.90%]. Protocol varied in terms of anodal or cathodal stimulation, areas of stimulation (M1 and DLPFC the most common), number of sessions (from 5 to 20) and current intensity (from 1 to 2 mA). The time of application was 20 min in 92% of protocols. In comparison with sham stimulation, tDCS demonstrated a superior effect in reducing chronic pain conditions. They give perspectives that the top-down neuromodulator effects of tDCS are a promising approach to improve management in refractory chronic not-cancer related pain and to enhance dysfunctional neuronal circuitries involved in the DPIS and other pain dimensions and improve pain control with a therapeutic opioid-free. However, further studies are needed to determine individualized protocols according to a biopsychosocial perspective.
PubMed: 31803005
DOI: 10.3389/fnins.2019.01218 -
Pain Feb 2020There has been an explosion of interest in the utility of cannabinoids as potential analgesics. This systematic review critically synthesizes the evidence for...
There has been an explosion of interest in the utility of cannabinoids as potential analgesics. This systematic review critically synthesizes the evidence for cannabinoid analgesic effects on quantitative sensory testing outcomes in both healthy adults and patients with chronic noncancer pain. Our systematic review protocol is preregistered on PROSPERO (CRD42018117367). An electronic search was made in PsycINFO, Cochrane, Google Scholar, Embase, and Pubmed of all literature published until August 2018. Of the 1217 studies found from the search, a total 39 placebo-controlled studies that met the eligibility criteria were synthesized for this study. Because of substantial heterogeneity of study designs, populations, cannabinoid compounds, and quantitative sensory testing outcomes, meta-analysis was not conducted. More consistent evidence of cannabinoid analgesia was observed for inhaled cannabis than synthetic cannabinoids. Analgesic effects were most commonly observed in tests of cold pain sensitivity, and hyperalgesic effects were most commonly observed in tests of electrical stimulation. Patterns of findings from studies with healthy subjects did not substantively differ from those with chronic noncancer pain. However, these observations are qualified by the high degree of inconsistency across studies and methodological heterogeneity. We offer recommendations for future studies to improve study rigor and reproducibility.
Topics: Analgesics; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Chronic Pain; Dronabinol; Humans; Hyperalgesia; Medical Marijuana; Pain Measurement; Pain Threshold
PubMed: 31613869
DOI: 10.1097/j.pain.0000000000001720 -
Canadian Journal of Pain = Revue... 2019: Complex regional pain syndrome (CRPS) is a chronic condition characterized by severe regional pain, allodynia, hyperalgesia, and functional impairment. The aim of this... (Review)
Review
: Complex regional pain syndrome (CRPS) is a chronic condition characterized by severe regional pain, allodynia, hyperalgesia, and functional impairment. The aim of this systematic review is to investigate whether a familial subtype of CRPS (fCRPS) exists and to determine whether people with fCRPS have specific characteristics. : Databases CINAHL, Medline, PsycINFO, and PubMed were searched with no date limitation. Quality of reporting was assessed using the Scottish Intercollegiate Guidelines Network scale and the Joanna Briggs Institute's checklists. : Eight studies were included. Family relationships were defined as any immediate (i.e., parents or siblings) or blood relatives. A combination of participants with known or unknown causes for CRPS was recruited. The studies in this review support the potential for the existence of fCRPS, although this included less than 25% of those affected. People with potential fCRPS showed more severe symptoms, more sites involved, a higher percentage of spontaneous onset, and earlier age at onset. An elevated sibling recurrence risk ratio of 5.6 (95% confidence interval [CI], 3.0 to 9.8) was reported for people under 50. None of the studies established a pattern of heritability. Therefore, the most likely explanation for heritability would be a multifactorial model in which cumulative and interactive Gene × Environment effects may be involved. : This systematic review supports the potential for the existence of fCRPS; however, all identified studies used uncontrolled case reports, case series, and case-control designs that cannot provide evidence of causation. Further studies are required to reveal the heritability and genetic structure of fCRPS.
PubMed: 35005404
DOI: 10.1080/24740527.2019.1637249 -
Journal of Pain Research 2019Endometriosis-associated pain afflicts an enormous number of women who suffer from endometriosis. There is an urgent need to explore the pathogenesis of... (Review)
Review
Endometriosis-associated pain afflicts an enormous number of women who suffer from endometriosis. There is an urgent need to explore the pathogenesis of endometriosis-associated pain to identify targets for treatment of hyperalgesia. A search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library using the search terms "endometriosis" AND ("pain" OR "hyperalgesia" OR "nociception" OR "allodynia") AND "central sensitization". The search was limited to articles published in English from 01/01/2008 to the present. Among the search results, 15 articles were eligible for systematic review, including 6 reviews, 6 human studies (one in the form of a conference abstract only), and 3 animal studies. The articles were classified into 4 lists to describe the mechanism of endometriosis-associated pain and synthesize different aspects of research on it. In conclusion, there is a need to explore the mechanism of endometriosis-associated pain in terms of innervation, vascularization, local inflammation, cross-correlated visceral sensitization, and central sensitization to identify the target molecules and signaling pathways of key genes and relevant biomarkers through new techniques, all with the goal of developing a more comprehensive treatment strategy for endometriosis than is currently available.
PubMed: 31190954
DOI: 10.2147/JPR.S197667 -
Pain Physician May 2019Postherpetic neuralgia, a persistent pain condition often characterized by allodynia and hyperalgesia, is a deleterious consequence experienced by patients after an...
BACKGROUND
Postherpetic neuralgia, a persistent pain condition often characterized by allodynia and hyperalgesia, is a deleterious consequence experienced by patients after an acute herpes zoster vesicular eruption has healed. The pain associated with postherpetic neuralgia can severely affect a patient's quality of life, quality of sleep, and ability to participate in activities of daily living. Currently, first-line treatments for this condition include the administration of medication therapies such as tricyclic antidepressants, pregabalin, gabapentin, and lidocaine patches, followed by the application of tramadol and capsaicin creams and patches as second- or third-line therapies. As not all patients respond to such conservative options, however, interventional therapies are valuable for those who continue to experience pain.
OBJECTIVE
This review focuses on interventional therapies that have been subjected to randomized controlled trials for the treatment of postherpetic neuralgia, including transcutaneous electrical nerve stimulation; local botulinum toxin A, cobalamin, and triamcinolone injection; intrathecal methylprednisolone and midazolam injection; stellate ganglion block; dorsal root ganglion destruction; and pulsed radiofrequency therapy.
STUDY DESIGN
Systematic review.
SETTING
Hospital department in Taiwan.
METHODS
Search of PubMed database for all randomized controlled trials regarding postherpetic neuralgia that were published before the end of May 2017.
RESULTS
The current evidence is insufficient for determining the single best interventional treatment. Considering invasiveness, price, and safety, the subcutaneous injection of botulinum toxin A or triamcinolone, transcutaneous electrical nerve stimulation, peripheral nerve stimulation, and stellate ganglion block are recommended first, followed by paravertebral block and pulsed radiofrequency. If severe pain persists, spinal cord stimulation could be considered. Given the destructiveness of dorsal root ganglion and adverse events of intrathecal methylprednisolone injection, these interventions should be carried out with great care and only following comprehensive discussion.
LIMITATIONS
Although few adverse effects were reported, these procedures are invasive, and a careful assessment of the risk-benefit ratio should be conducted prior to administration.
CONCLUSION
With the exception of intrathecal methylprednisolone injection for postherpetic neuralgia, the evidence for most interventional procedures used to treat postherpetic neuralgia is Level 2, according to "The Oxford Levels of Evidence 2". Therefore, these modalities have received only grade B recommendations. Despite the lack of a high level of evidence, spinal cord stimulation and peripheral nerve stimulation are possibly useful for the treatment of postherpetic neuralgia.
KEY WORDS
Interventional treatment, postherpetic neuralgia, botulinum toxin, steroid, stellate ganglion block, peripheral nerve stimulation, paravertebral block, radiofrequency, spinal cord stimulation.
Topics: Female; Humans; Male; Neuralgia, Postherpetic; Pain Management; Randomized Controlled Trials as Topic
PubMed: 31151330
DOI: No ID Found