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Ageing Research Reviews May 2017While hyperalgesia (increased pain sensitivity) has been suggested to contribute to the increased prevalence of clinical pain in Parkinson's disease (PD), experimental... (Meta-Analysis)
Meta-Analysis Review
While hyperalgesia (increased pain sensitivity) has been suggested to contribute to the increased prevalence of clinical pain in Parkinson's disease (PD), experimental research is equivocal and mechanisms are poorly understood. We conducted a meta-analysis of studies comparing PD patients to healthy controls (HCs) in their response to experimental pain stimuli. Articles were acquired through systematic searches of major databases from inception until 10/2016. Twenty-six studies met inclusion criteria, comprising 1292 participants (PD=739, HCs=553). Random effects meta-analysis of standardized mean differences (SMD) revealed lower pain threshold (indicating hyperalgesia) in PD patients during unmedicated OFF states (SMD=0.51) which was attenuated during dopamine-medicated ON states (SMD=0.23), but unaffected by age, PD duration or PD severity. Analysis of 6 studies employing suprathreshold stimulation paradigms indicated greater pain in PD patients, just failing to reach significance (SMD=0.30, p=0.06). These findings (a) support the existence of hyperalgesia in PD, which could contribute to the onset/intensity of clinical pain, and (b) implicate dopamine deficiency as a potential underlying mechanism, which may present opportunities for the development of novel analgesic strategies.
Topics: Dopamine; Humans; Hyperalgesia; Pain Perception; Parkinson Disease
PubMed: 28179128
DOI: 10.1016/j.arr.2017.01.005 -
Journal of Orthopaedics and... Mar 2017Whiplash injuries are among the leading injuries related to car crashes and it is important to determine the prognostic factors that predict the outcome of patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Whiplash injuries are among the leading injuries related to car crashes and it is important to determine the prognostic factors that predict the outcome of patients with these injuries. This meta-review aims to identify factors that are associated with outcome after acute whiplash injury.
MATERIALS AND METHODS
A systematic search for all systematic reviews on outcome prediction of acute whiplash injury was conducted across several electronic databases. The search was limited to publications in English, and there were no geographical or time of publication restrictions. Quality appraisal was conducted with A Measurement Tool to Assess Systematic Reviews.
RESULTS
The initial search yielded 207 abstracts; of these, 195 were subsequently excluded by topic or method. Twelve systematic reviews with moderate quality were subsequently included in the analysis. Post-injury pain and disability, whiplash grades, cold hyperalgesia, post-injury anxiety, catastrophizing, compensation and legal factors, and early healthcare use were associated with continuation of pain and disability in patients with whiplash injury. Post-injury magnetic resonance imaging or radiographic findings, motor dysfunctions, or factors related to the collision were not associated with continuation of pain and disability in patients with whiplash injury. Evidence on demographic and three psychological factors and prior pain was conflicting, and there is a shortage of evidence related to the significance of genetic factors.
CONCLUSIONS
This meta-review suggests an association between initial pain and anxiety and the outcome of acute whiplash injury, and less evidence for an association with physical factors.
LEVEL OF EVIDENCE
Level 1.
Topics: Accidents, Traffic; Humans; Risk Factors; Treatment Outcome; Whiplash Injuries
PubMed: 27738773
DOI: 10.1007/s10195-016-0431-x -
Muscle & Nerve Mar 2017No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes... (Review)
Review
INTRODUCTION
No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures.
METHODS
This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy.
RESULTS
Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included.
CONCLUSIONS
Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017.
Topics: Diabetic Neuropathies; HIV Infections; Humans; Peripheral Nervous System Diseases
PubMed: 27447116
DOI: 10.1002/mus.25264 -
Pain Physician 2015Characterization of the prognostic variables for persistent neuropathic pain (PNP) remains incomplete despite multiple articles addressing this topic. To provide more... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Characterization of the prognostic variables for persistent neuropathic pain (PNP) remains incomplete despite multiple articles addressing this topic. To provide more insight into the recovery and prognosis of neuropathic pain, high-quality data are required that provide information about the predictors that contribute to the development of PNP.
OBJECTIVE
To determine the methodological quality of studies about predictors for PNP and to summarize findings of predictors found in high-quality studies.
STUDY DESIGN
A systematic review.
SETTING
VU University Medical Center, Amsterdam, The Netherlands.
METHODS
Studies were identified by searching the electronic databases PubMed, Embase, and Cochrane Library. Methodological quality of each article was independently assessed by 2 reviewers.
RESULTS
Forty-six relevant studies were identified, classified into 4 different neuropathic pain (NP)-syndromes: postherpetic neuralgia (n = 35), radicular pain and sciatica (n = 3), postsurgical pain (n = 6), and other types of NP (n = 2). Seven studies were of high quality. The 3 high-quality studies found for PHN reported male gender, older age, smoking, trauma at the site of lesion, missed antiviral prescriptions, higher acute pain severity, higher rash severity, more neuropathic characteristics, shorter rash duration, and a lower health status as predictors for PNP. For persistence of radicular pain one high-quality study reported negative outcome expectancies, pain-related fear of movement, and passive pain coping as predictors for PNP. Psychological distress, acute pain, breast cancer surgery, higher body mass index, area of secondary hyperalgesia, neuropathic characteristics, hypoesthesia, and hyperesthesia were found to be predictive for postsurgical pain in 3 high-quality studies.
LIMITATIONS
Some publications may have been missed during literature search. The low-quality of the studies could be the result of an incomplete description of their methods.
CONCLUSIONS
High-quality studies mainly assessed factors related to disease functions and structures. Due to shortcomings in methodological quality and limited areas of predictor selection, there is a need for high-quality studies focusing on predictor measurement, statistical analysis and the use of a standardized set of predictors.
Topics: Adult; Aged; Chronic Pain; Female; Humans; Male; Middle Aged; Neuralgia; Neuralgia, Postherpetic; Pain, Postoperative
PubMed: 26431122
DOI: No ID Found -
PloS One 2015Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The... (Review)
Review
Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double-blind studies using 'inhibitory' or 'sensitizing', physiological test paradigms in healthy human subjects. The databases PubMed and Embase were searched according to predefined criteria. Out of a total of 2,142 records, 63 studies (1,477 subjects [male/female ratio = 1.5]) were considered relevant. Twenty-five studies utilized 'inhibitory' test paradigms (ITP) and 38 studies utilized 'sensitizing' test paradigms (STP). The ITP-studies were characterized as conditioning modulation models (22 studies) and repetitive transcranial magnetic stimulation models (rTMS; 3 studies), and, the STP-studies as secondary hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and rTMS. In the remaining 14 conditioning modulation studies either absence of effects or ambiguous effects by MOR-antagonists, were observed. In the STP-studies, no effect of the opioid-blockade could be demonstrated in 5 out of 6 secondary hyperalgesia studies. The direction of MOR-antagonist dependent effects upon pain ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect, presumably mediated by an EOS-dependent mechanisms of analgesia and hyperalgesia.
Topics: Analgesia; Analgesics, Opioid; Animals; Female; Humans; Male; Narcotic Antagonists; Pain Management; Randomized Controlled Trials as Topic
PubMed: 26029906
DOI: 10.1371/journal.pone.0125887 -
Biology of Blood and Marrow... Sep 2015Stem cell transplantation has been considered a possible therapeutic method for neuropathic pain. However, no quantitative data synthesis of stem cell therapy for... (Meta-Analysis)
Meta-Analysis Review
Stem cell transplantation has been considered a possible therapeutic method for neuropathic pain. However, no quantitative data synthesis of stem cell therapy for neuropathic pain exists. Therefore, the present systematic review and meta-analysis assessed the efficacy of bone marrow mesenchymal stem cell (BMMSC) transplantation on alleviating pain symptoms in animal models of neuropathic pain. In the present meta-analysis, controlled animal studies assessing the effect of administrating BMMSC on neuropathic pain were included through an extensive literature search of online databases. After collecting data, effect sizes were computed and the standardized mean difference (SMD) with 95% confidence interval (CI) was entered in all analyses. Random-effects models were used for data analysis. Sensitivity and subgroup analyses were performed to investigate expected or measured heterogeneity. Finally, 14 study were included. The analyses showed that BMMSC transplantation lead to significant improvement on allodynia (SMD = 2.06; 95% CI, 1.09 to 3.03; I(2) = 99.7%; P < .001). The type of neuropathy (P = .036), time between injury and intervention (P = .02), and the number of transplanted cells (P = .023) influence the improvement of allodynia after BMMSC transplantation. BMMSC transplantation has no effect on hyperalgesia (SMD = .3; 95% CI, -1.09 to 1.68; I(2) = 100%; P < .001) unless it occurs during the first 4 days after injury (P = .02). The present systematic review with meta-analysis suggests that BMMSC transplantation improves allodynia but does not have any significant effect on hyperalgesia unless it is given during the first 4 days after injury.
Topics: Animals; Bone Marrow Cells; Hyperalgesia; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neuralgia
PubMed: 25985918
DOI: 10.1016/j.bbmt.2015.05.008 -
Pediatric Blood & Cancer Sep 2015Novel insights into the neurobiology of sickle cell disease (SCD) pain have recently been discovered. We systematically reviewed the literature focusing on original... (Review)
Review
Novel insights into the neurobiology of sickle cell disease (SCD) pain have recently been discovered. We systematically reviewed the literature focusing on original research that examined the biology of pain in SCD and/or addressed assessment or treatment of neuropathic pain in SCD. This review of 15 articles that met inclusion criteria provides epidemiological, basic, and clinical data that support central and/or peripheral nervous system abnormalities likely contribute to sickle cell pain. Continued basic and clinical investigation into pain neurobiology is imperative to translate these discoveries into novel ways to assess and treat neuropathic pain and decrease patient suffering.
Topics: Anemia, Sickle Cell; Animals; Central Nervous System Sensitization; Clinical Trials as Topic; Cross-Sectional Studies; Databases, Factual; Disease Models, Animal; Forecasting; Humans; Hyperalgesia; Mice; Models, Neurological; Neuralgia; Pain Management; Pain Measurement; Peripheral Nervous System; Risk Factors; Self Report; Surveys and Questionnaires
PubMed: 25976161
DOI: 10.1002/pbc.25574 -
Osteoarthritis and Cartilage Jul 2015Emerging evidence suggests that pain sensitization plays an important role in pain associated with knee osteoarthritis (OA). This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Emerging evidence suggests that pain sensitization plays an important role in pain associated with knee osteoarthritis (OA). This systematic review and meta-analysis examined the evidence for pain sensitization in people with knee OA and the relationship between pain sensitization and symptom severity.
METHODS
A search of electronic databases and reference lists was carried out. All full text observational studies published between 2000 and 2014 with the aim of investigating pain sensitization in humans with knee OA using quantitative sensory testing (QST) measures of hyperalgesia and central hyperexcitability were eligible for inclusion. Meta-analysis of data was carried out using a random effects model, which included results comparing knee OA participants to controls, and results comparing high symptom severity to low symptom severity.
RESULTS
Fifteen studies were identified following screening and quality appraisal. For the meta-analysis, pressure pain threshold (PPT) and heat pain threshold (HPT) means and standard deviations were pooled using random effects models. The point estimate was large for differences in PPTs between knee OA participants and controls [-0.85; confidence interval (CI): -1.1 to -0.6], and moderate for PPT differences between knee OA participants with high symptom severity vs those with low symptom severity (0.51; CI: -0.73 to -0.30). A small point estimate was found for differences in HPTs between knee OA participants and controls (-0.42; CI: -0.87 to 0.02).
CONCLUSION
Evidence from this systematic review and meta-analysis suggests that pain sensitization is present in people with knee OA and may be associated with knee OA symptom severity.
Topics: Humans; Hyperalgesia; Osteoarthritis, Knee; Pain; Pain Measurement; Pain Threshold
PubMed: 25749012
DOI: 10.1016/j.joca.2015.02.163 -
Brazilian Oral Research 2015A systematic review was conducted to identify reliable somatosensory evaluation methods for atypical odontalgia (AO) patients. The computerized search included the main... (Review)
Review
A systematic review was conducted to identify reliable somatosensory evaluation methods for atypical odontalgia (AO) patients. The computerized search included the main databases (MEDLINE, EMBASE, and Cochrane Library). The studies included used the following quantitative sensory testing (QST) methods: mechanical detection threshold (MDT), mechanical pain threshold (MPT) (pinprick), pressure pain threshold (PPT), dynamic mechanical allodynia with a cotton swab (DMA1) or a brush (DMA2), warm detection threshold (WDT), cold detection threshold (CDT), heat pain threshold (HPT), cold pain detection (CPT), and/or wind-up ratio (WUR). The publications meeting the inclusion criteria revealed that only mechanical allodynia tests (DMA1, DMA2, and WUR) were significantly higher and pain threshold tests to heat stimulation (HPT) were significantly lower in the affected side, compared with the contralateral side, in AO patients; however, for MDT, MPT, PPT, CDT, and WDT, the results were not significant. These data support the presence of central sensitization features, such as allodynia and temporal summation. In contrast, considerable inconsistencies between studies were found when AO patients were compared with healthy subjects. In clinical settings, the most reliable evaluation method for AO in patients with persistent idiopathic facial pain would be intraindividual assessments using HPT or mechanical allodynia tests.
Topics: Adult; Facial Pain; Female; Humans; Male; Middle Aged; Pain Measurement; Pain Threshold; Physical Stimulation; Randomized Controlled Trials as Topic; Toothache
PubMed: 25627886
DOI: 10.1590/1807-3107BOR-2015.vol29.0020 -
Anesthesiology Mar 2015Opioid-induced hyperalgesia is a clinical syndrome whereby patients on long-term opioids become more sensitive to pain while taking opioids. Opioid-induced hyperalgesia... (Review)
Review
BACKGROUND
Opioid-induced hyperalgesia is a clinical syndrome whereby patients on long-term opioids become more sensitive to pain while taking opioids. Opioid-induced hyperalgesia is characterized by increased pain intensity over time, spreading of pain to other locations, and increased pain sensation to external stimuli. To characterize opioid-induced hyperalgesia, laboratory methods to measure hyperalgesia have been developed. To determine the performance of these methods, the authors conducted a systematic review of clinical studies that incorporate measures of hyperalgesia in chronic pain patients on long-term opioids.
METHODS
PubMed and Cochrane databases were searched (terms: opioid induced hyperalgesia, study or trial, and long-term or chronic). Studies published in English were selected if they were conducted in chronic pain patients on long-term opioids and incorporated measures of hyperalgesia; acute/single-dose studies and/or conducted in healthy volunteers were excluded.
RESULTS
Fourteen articles made the final selection (11 were selected from the search and 3 others were found from additional sources); there was one randomized controlled trial, one prospective controlled study, three prospective uncontrolled studies, and nine cross-sectional observation studies. Hyperalgesia measurement paradigms used included cold pain, heat pain, pressure pain, electrical pain, ischemic pain, and injection pain. Although none of the stimuli were capable of detecting patients' hyperalgesia, heat pain sensitivity showed some promising results.
CONCLUSIONS
None of the measures reviewed herein met the criteria of a definitive standard for the measurement of hyperalgesia. Additional studies that use improved study design should be conducted.
Topics: Analgesics, Opioid; Chronic Pain; Clinical Trials as Topic; Drug Administration Schedule; Humans; Hyperalgesia
PubMed: 25437498
DOI: 10.1097/ALN.0000000000000530