Conditioned Pain Modulation and Temporal Summation of Pain in Patients With Traumatic and Non-Specific Neck Pain: A Systematic Review and Meta-Analysis.

In patients with neck pain, it is unclear whether pain inhibition and facilitation endogenous pain mechanisms are altered. This systematic review and meta-analysis aimed to improve their understanding by assessing conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with neck pain associated with whiplash-associated disorders (WAD) or of a nonspecific neck pain (NSNP) nature compared to pain-free controls. Very low certainty evidence suggests: impaired CPM when assessed remotely in chronic WAD patients (n = 7, 230 patients and 204 controls, standardized mean differences (SMD) = -.47 [-.89 to -.04]; P = .04) but not locally (n = 6, 155 patients and 150 controls; SMD = -.34 [-.68 to .01]; P = .05), impaired CPM in chronic NSNP patients when assessed locally (n = 5, 223 patients and 162 controls; SMD = -.55 [-1.04 to -.06]; P = .04) but not remotely (n = 3, 72 patients and 66 controls; SMD = -.33 [-.92 to .25]; P = .13), TSP not facilitated in either chronic WAD (local TSP: n = 4, 90 patients and 87 controls; SMD = .68 [-.62 to 1.99]) (remote TSP: n = 8, 254 patients and 214 controls; SMD = .18 [-.12 to .48]) or chronic NSNP (local TSP: n = 2, 139 patients and 92 controls; SMD = .21 [-1.00 to 1.41]), (remote TSP: n = 3; 91 patients and 352 controls; SMD = .60 [-1.33 to 2.52]). The evidence is very uncertain whether CPM is impaired and TSP facilitated in patients with WAD and NSNP. PERSPECTIVE: This review and meta-analysis present the current evidence on CPM and TSP in patients with WAD and NSNP. Standardization of measurement methodology is needed to draw clear conclusions. Subsequently, future studies should investigate the clinical relevance of these measurements as prognostic variables or predictors of treatment success.

Conditioned pain modulation and psychological factors in young adults with recurrent or chronic neck pain.

BACKGROUND: Controversy exists with the presence of alterations in descending pain inhibition mechanisms in patients with non-specific neck pain (NSNP). The aim of the present study was to evaluate the status of conditioned pain modulation CPM, remote pressure pain thresholds (PPT), and psychological factors in a specific subgroup of patients with NSNP such as young adult students. In addition, possible associations between CPM, psychological factors, and pain characteristics were analyzed. METHODS: Thirty students with recurrent or chronic NSNP and 30 pain-free students were included in this cross-sectional study. The following measures were assessed: CPM, remote PPT, psychological factors (depression, anxiety, pain catastrophizing, and kinesiophobia), pain characteristics (duration, intensity, severity of chronic pain, interference with daily life), and central sensitization inventory (CSI). RESULTS: No significant differences were found in the efficacy of CPM between students with chronic or recurrent NSNP and pain-free students (ß coefficient = -0.67; 95% CI = -1.54, 0.20). However, students with pain showed a significantly higher remote PPT (mean difference = -1.94; 95% CI = -2.71, -1.18). and a greater presence of anxious (mean difference = 6; 95% CI = 2, 9) and depressive symptoms (mean difference = 8.57; 95% CI = 3.97, 13.16). In addition, significant moderate or strong correlations were found between CPM and pain intensity (partial r = 0.41), pain catastrophizing and mean pain intensity (r = 0.37), grade (r = 0.50), and interference of pain (r = 0.57), kinesiophobia and disability (r = 0.38), and depression and CSI (r = 0.39). CONCLUSIONS: Young adult students with chronic or recurrent NSNP present remote hyperalgesia and symptoms of depression and anxiety but not dysfunctional CPM.

Effectiveness of deep dry needling versus manual therapy in the treatment of myofascial temporomandibular disorders: a systematic review and network meta-analysis.

BACKGROUND: Temporomandibular disorders (TMDs) are the most common cause of orofacial pain of non-dental origin, with approximately 42% of diagnoses corresponding to myofascial pain. Manual therapy and dry needling are commonly used interventions for the treatment of myofascial temporomandibular disorders. However, it is unclear whether one of them could be superior to the other. OBJECTIVES: The aim of the present systematic review and network meta-analysis was to compare the effectiveness of manual therapy and dry needling in patients with myofascial TMD. METHODS: This is a systematic review and network meta-analysis. Randomized clinical trials were searched in the databases of Pubmed, PEDro, CINAHL, Web of Science, Scopus, Cochrane, Google Academic and EMBASE. The methodological quality of studies included in this review was judged using the Physiotherapy Evidence Database (PEDro) scale. A frequentist network meta-analysis was carried out, assuming random effects, to estimate the effects of interventions for temporomandibular joint pain measured on a 10-point visual analogue scale. RESULTS: Out of 3190 records identified, 17 met the inclusion criteria for qualitative analysis and eight were included in the network meta-analysis. Indirect comparisons between dry needling and manual therapy showed no significant differences in their effects on pain reduction (Odds Ratio [95%CI]; - 0.263 [- 1.517, 0.992]). The ranking of treatments shows that manual therapy (SUCRA = 0.932) followed by deep dry needling (SUCRA = 0.775) present the highest values of estimation and can be considered the most likely to reduce pain. CONCLUSIONS: The results of the network meta-analysis should be considered with caution due to the low quality of the evidence available and the high variability of the study protocols in terms of the method of application of dry needling and manual therapy interventions. PROSPERO under identifier: (CRD42020186470).

Reply to Rossettini et al. "Do Not Mix Apples with Oranges" to Avoid Misinterpretation of Placebo Effects in Manual Therapy: The Risk Is Resulting in a Fruit Basket. Comment on "Molina-Álvarez et al. Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2022, 19, 14021".

We have thoroughly reviewed and carefully analyzed the points raised in the comment titled: "Do not mix apples with oranges" to avoid misinterpretation of placebo effects in manual therapy: the risk is resulting in a fruit basket [...].

Manual Therapy Effects on Nonspecific Neck Pain Are Not Mediated by Mechanisms Related to Conditioned Pain Modulation: A Randomized Clinical Trial.

BACKGROUND: Manual therapy (MT) is a treatment recommended by clinical practice guidelines in the management of patients with neck pain. However, the mechanisms through which MT works remain unknown. The aim of the present study is to investigate if MT is mediated by mechanisms related to conditioned pain modulation (CPM), comparing the effects of painful with a pain-free MT treatment. METHODS: A two-arm, parallel, randomized controlled clinical trial with concealed allocation and blinding of the outcome assessor was conducted in university students with chronic or recurrent nonspecific neck pain (NSNP). Participants received either a painful or pain-free MT session. Psychophysical variables including pressure pain thresholds, CPM, temporal summation of pain and cold pain intensity were assessed before and immediately after treatment. In addition, changes in neck pain intensity over the following 7 days and self-perceived improvement immediately and 7 days after treatment were assessed. RESULTS: No significant differences were found between groups in any of the psychophysical variables or in patients' self-perceived improvement. Only a significantly greater decrease in neck pain intensity immediately after treatment was found in the pain-free MT group compared to the painful MT group. CONCLUSION: The results suggest that the immediate and short-term effects of MT on NSNP are not mediated by CPM-related mechanisms.

Psychometric properties of quantitative sensory testing in healthy and patients with shoulder pain: A systematic review.

Quantitative Sensory Testing (QST) is a psychophysical battery of various tests developed to quantify the subjects' self-reported sensory experience. Although the use of QST is valuable for the clinical assessment of pain, standard evaluation protocols have not yet been established. This systematic review aimed to investigate the level of evidence for the psychometric properties of QST in healthy and patients with shoulder pain. Eight databases were searched for peer-reviewed studies published until August 2021. The methodological quality of studies was evaluated using the COSMIN checklist. Twelve studies were included for qualitative synthesis, which included three different tests (Pressure Pain Threshold (PPT), Conditioned Pain Modulation (CPM) and Temporal Summation (TS)). As the body of evidence consisted of studies of low methodological quality, the psychometric properties of PPT, CPM, and TS in healthy and patients with shoulder pain were classified as unknown. Although there is a risk that the conclusions may be 'superficial' in nature, the reliability seems to be nearly excellent for the PPT, however, the protocols' variation and the low methodological quality of the studies do not allow for clear conclusions. Further studies are required for the CPM and TS in patients with shoulder pain.

Effects of Orthopedic Manual Therapy on Pain Sensitization in Patients With Chronic Musculoskeletal Pain: An Umbrella Review With Meta-Meta-analysis.

OBJECTIVE: The aim of this umbrella review with meta-meta-analysis was to assess the effectiveness of orthopedic manual therapy in isolation on pain sensitization in patients with chronic musculoskeletal pain. DESIGN: A systematic search was performed in different databases including systematic reviews with or without meta-analysis. The outcome measures included were pressure pain threshold, temporal summation, and conditioned pain modulation. The results of the different reviews were statistically synthesized through a random-effect meta-analysis, of all standardized mean differences and the corresponding 95% confidence interval reported by each study. RESULTS: For mechanical hyperalgesia, the meta-meta-analysis of three meta-analyses revealed a statistically significant small-moderate effect of orthopedic manual therapy, with no evidence of heterogeneity and moderate-quality evidence. In terms of temporal summation, one meta-analysis revealed a statistically significant small effect of orthopedic manual therapy intervention, with moderate heterogeneity and low quality of evidence. Finally, one review without meta-analysis found that orthopedic manual therapy improved endogenous analgesia with low-quality evidence. CONCLUSION: Orthopedic manual therapy in isolation improved mechanical hyperalgesia with moderate-quality evidence, as well as temporal summation and conditioned pain modulation with low-quality evidence. However, its effects are limited only to immediate and short-term.

Effect of Different Physical Therapy Interventions on Brain-Derived Neurotrophic Factor Levels in Chronic Musculoskeletal Pain Patients: A Systematic Review.

OBJECTIVE: The main objectives of this review were, firstly, to study the effect of different physiotherapy interventions on BDNF levels, and, secondly, to analyze the influence of physiotherapy on pain levels to subsequently draw conclusions about its possible relationship with BDNF. BACKGROUND: Based on the theory that neurotrophic factors such as BDNF play a fundamental role in the initiation and/or maintenance of hyperexcitability of central neurons in pain, it was hypothesized that the levels of this neurotrophic factor may be modified by the application of therapeutic interventions, favoring a reduction in pain intensity. METHODS: A literature search of multiple electronic databases (Pubmed, PsycINFO, Medline (Ebsco), Scopus, WOS, Embase) was conducted to identify randomized control trials (RCTs) published without language restrictions up to and including March 2022. The search strategy was based on the combination of medical terms (Mesh) and keywords relating to the following concepts: "pain", "chronic pain", "brain derived neurotrophic factor", "BDNF", "physiotherapy", and "physical therapy". A total of seven papers were included. RESULTS: There were two studies that showed statistically significant differences in pain intensity reduction and an increase in the BDNF levels that used therapies such as rTMS and EIMS in patients with chronic myofascial pain. However, the same conclusions cannot be drawn for the other physical therapies applied. CONCLUSIONS: rTMS and EIMS interventions achieved greater short-term reductions in pain intensity and increased BDNF over other types of interventions in chronic myofascial pain patients, as demonstrated by a moderate amount of evidence. In contrast, other types of physical therapy (PT) interventions did not appear to be more effective in decreasing pain intensity and increasing BDNF levels than placebo PT or minimal intervention, as a low amount of evidence was found.

Effects of Percutaneous and Transcutaneous Electrical Nerve Stimulation on Endogenous Pain Mechanisms in Patients with Musculoskeletal Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: The main aim was to determine the effects of percutaneous electrical nerve stimulation (PENS) and transcutaneous electrical nerve stimulation (TENS) on endogenous pain mechanisms in patients with musculoskeletal pain. DESIGN: A systematic review and meta-analysis. METHODS: The search was conducted on March 1, 2022, in the EMBASE, CINAHL, PubMed, PEDro, Cochrane Library, Web of Science, Medline, and SCOPUS databases. Randomized controlled trials comparing the use of transcutaneous or percutaneous electrostimulation with a placebo, control group, or standard treatment in patients with musculoskeletal pain were included. Outcome measurements were quantitative sensory testing somatosensory variables like pressure pain threshold (PPT), conditioned pain modulation, and temporal summation of pain. The pooled data were evaluated in Review Manager 5.4. RESULTS: Twenty-four randomized controlled trials (n = 24) were included in the qualitative analysis and 23 in the meta-analysis. The immediate effects of PENS and TENS on local PPTs were significant, with a moderate effect size (standardized mean difference [SMD] 0.53; 95% confidence interval [CI]: 0.34 to 0.72; P < 0.00001). When only studies with a lower risk of bias were analyzed, the heterogeneity decreased from I2 = 58% (P < 0.00001) to I2 = 15% (P = 0.01), and a decrease in the overall effect was observed (SMD 0.33; 95% CI: 0.7 to 0.58). The short-term effects on local PPTs were not significant when compared with the control group (P = 0.13). The mid-term effects on local PPTs were significant, showing a large effect size (SMD 0.55; 95% CI: 0.9 to 1.00; P = 0.02). The immediate effects on conditioned pain modulation were significant, with a large effect size (SMD 0.94; 95% CI: 0.48 to 1.41; P < 0.0001). CONCLUSION: PENS and TENS have a mild-moderate immediate effect on local mechanical hyperalgesia in patients with musculoskeletal pain. It appears that these effects are not sustained over time. Analyses suggest an effect on central pain mechanisms producing a moderate increase in remote PPT, an increase in conditioned pain modulation, but further studies are needed to draw clearer conclusions.

Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis.

PURPOSE: Background: Evaluate whether the design of placebo control groups could produce different interpretations of the efficacy of manual therapy techniques. METHODS: Nine databases were searched (EMBASE, CINAHL, PsycINFO, MEDLINE, PubMed, SCOPUS, WEB of SCIENCE, COCHRANE, and PEDro). Randomized placebo-controlled clinical trials that used manual therapy as a sham treatment on subjects suffering from pain were included. Data were summarized qualitatively, and meta-analyses were conducted with R. RESULTS: 53 articles were included in the qualitative analysis and 48 were included in the quantitative analyses. Manipulation techniques did not show higher effectiveness when compared with all types of sham groups that were analyzed (SMD 0.28; 95%CI [-0.24; 0.80]) (SMD 0.28; 95%CI [-0.08; 0.64]) (SMD 0.42; 95%CI [0.16; 0.67]) (SMD 0.82; 95%CI [-0.57; 2.21]), raising doubts on their therapeutic effect. Factors such as expectations of treatment were not consistently evaluated, and analysis could help clarify the effect of different sham groups. As for soft tissue techniques, the results are stronger in favor of these techniques when compared to sham control groups (SMD 0.40; 95%CI [0.19, 0.61]). Regarding mobilization techniques and neural gliding techniques, not enough studies were found for conclusions to be made. CONCLUSIONS: The literature presents a lack of a unified placebo control group design for each technique and an absence of assessment of expectations. These two issues might account for the unclear results obtained in the analysis.

Effect of Physiotherapeutic Interventions on Biomarkers of Neuropathic Pain: A Systematic Review of Preclinical Literature.

The purpose of this systematic review was to evaluate the effects of physiotherapeutic interventions on biomarkers of neuropathic pain in preclinical models of peripheral neuropathic pain (PNP). The search was performed in Pubmed, Web of Science, EMBASE, Cochrane, Cinhal, Psycinfo, Scopus, Medline, and Science Direct. Studies evaluating any type of physiotherapy intervention for PNP (systemic or traumatic) were included. Eighty-one articles were included in this review. The most common PNP model was chronic constriction injury, and the most frequently studied biomarkers were related to neuro-immune processes. Exercise therapy and Electro-acupuncture were the 2 most frequently studied physiotherapy interventions while acupuncture and joint mobilization were less frequently examined. Most physiotherapeutic interventions modulated the expression of biomarkers related to neuropathic pain. Whereas the results seem promising; they have to be considered with caution due to the high risk of bias of included studies and high heterogeneity of the type and anatomical localization of biomarkers reported. The review protocol is registered on PROSPERO (CRD42019142878). PERSPECTIVE: This article presents the current evidence about physiotherapeutic interventions on biomarkers of neuropathic pain in preclinical models of peripheral neuropathic pain. Existing findings are reviewed, and relevant data are provided on the effectiveness of each physiotherapeutic modality, as well as its certainty of evidence and clinical applicability.

Effectiveness of Neural Mobilization Techniques in the Management of Musculoskeletal Neck Disorders with Nerve-Related Symptoms: A Systematic Review and Meta-Analysis with a Mapping Report.

OBJECTIVE: The objective was to assess the effectiveness of neural mobilization (NM) techniques in the management of musculoskeletal neck disorders with nerve-related symptoms (MND-NRS). METHODS: We conducted a systematic review with meta-analysis, using pain intensity, disability, perceived function, cervical range of motion, and mechanosensitivity as the main outcome measures. RESULTS: The systematic review included 22 studies (n = 978). More favorable outcomes were observed for NM on pain intensity compared with control interventions (standardized mean differences (SMDs) -0.92; 95% CI -1.66-0.18), but not compared with other treatments (OTs) (SMD 1.06; 95% CI -0.02 to 2.15). Regarding neck pain intensity, no significant differences were found in favor of NM compared with OTs (SMD 0.37; 95% CI -0.35 to 1.1). However, between-treatment differences were found in favor of OT on arm-pain intensity (SMD 0.57; 95% CI 0.08-1.05). In addition, the grouped MA did not show statistically significant differences between NM and OT outcomes on the cervical range of motion (SMD 0.16; 95% CI -0.06 to 0.38). However, compared with no intervention, NM was associated with significantly improved outcomes in cervical rotation (SMD 0.91; 95% CI 0.61-1.22). Similar results were found regarding disability (SMD -0.08; 95% CI -0.36-0.20, and SMD -1.44; 95% CI -2.28-0.6, respectively). Finally, NM was associated with more favorable outcomes on mechanosensitivity compared with OT (SMD 0.79; 95% CI 0.15-1.42) and greater improvements in function compared with no intervention (SMD 0.89; 95% CI 0.16-1.62). CONCLUSIONS: NM appeared to be effective to improve overall pain intensity when embedded in a physiotherapy treatment in the management of MND-NRS. When compared with no intervention, it was effective to improve neck rotation, disability, and function. However, it was not superior to other types of treatments in improving overall pain intensity, neck pain intensity, arm pain intensity, cervical range of motion and disability, except for mechanosensitivity.

Prediction of Patient Satisfaction after Treatment of Chronic Neck Pain with Mulligan's Mobilization.

Chronic neck pain is among the most common types of musculoskeletal pain. Manual therapy has been shown to have positive effects on this type of pain, but there are not yet many predictive models for determining how best to apply manual therapy to the different subtypes of neck pain. The aim of this study is to develop a predictive learning approach to determine which basal outcome could give a prognostic value (Global Rating of Change, GRoC scale) for Mulligan's mobilization technique and to identify the most important predictive factors for recovery in chronic neck pain subjects in four key areas: the number of treatments, time of treatment, reduction of pain, and range of motion (ROM) increase. A prospective cohort dataset of 80 participants with chronic neck pain diagnosed by their family doctor was analyzed. Logistic regression and machine learning modeling techniques (Generalized Boosted Models, Support Vector Machine, Kernel, Classsification and Decision Trees, Random Forest and Neural Networks) were each used to form a prognostic model for each of the nine outcomes obtained before and after intervention: disability-neck disability index (NDI), patient satisfaction (GRoC), quality of life (12-Item Short Form Survey, SF-12), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI II), pain catastrophizing scale (ECD), kinesiophobia-Tampa scale of kinesiophobia (TSK-11), Pain Intensity Visual Analogue Scale (VAS), and cervical ROM. Pain descriptions from the subjects and pain body diagrams guided the physical examination. The most important predictive factors for recovery in chronic neck pain patients indicated that the more anxiety and the lower the ROM of lateroflexion, the higher the probability of success with the Mulligan concept treatment.

Median Nerve Neural Mobilization Adds No Additional Benefit When Combined with Cervical Lateral Glide in the Treatment of Neck Pain: A Randomized Clinical Trial.

BACKGROUND: This study aimed to compare the effectiveness of cervical lateral glide (CLG) added to median nerve neural mobilization (MNNM) in patients with neck pain (NP). METHODS: A single-blinded randomized controlled clinical trial was carried out in a Pain Management Unit from a Hospital. A total sample of 72 patients with NP was recruited from a hospital. Patients were randomized to receive isolated CLG (n = 36) or CLG + MNNM (n = 36). Bilateral elbow extension range of motion (ROM) on upper limb neurodynamic test 1 (ULNT1), bilateral pressure pain thresholds (PPT) on the median nerve at elbow joint, C6 zygapophyseal joint and tibialis anterior, Visual analogue scale (VAS), body chart distribution of pain, active cervical ROM (CROM), Neck Disability Index (NDI), and Tampa Scale of Kinesiophobia (TSK-11) were measured at baseline as well as immediately, 15 days, and 1 month after treatment. RESULTS: There were no statistically significant interactions (p > 0.05) between treatment and time for median nerve mechanosensitivity outcomes, pain intensity, symptom distribution, and PPT of the widespread pain assessment, as well as cervical function, and kinesiophobia. CONCLUSIONS: MNNM gave no additional benefit to CLG in patients with NP regarding pain intensity, symptom distribution, mechanosensitivity, functionality, and kinesiophobia. Only two treatment sessions and the short follow-up are important issues, therefore, justifying further studies to answer the research question with better methodology.

Efficacy of Physical Therapy on Nociceptive Pain Processing Alterations in Patients with Chronic Musculoskeletal Pain: A Systematic Review and Meta-analysis.

INTRODUCTION: Chronic musculoskeletal pain is a major health, social, and economic problem. Most of the subjects who suffer from chronic musculoskeletal pain present processes of central sensitization. Temporal summation and conditioned pain modulation are the two most commonly used clinical measures of this. The objective of this review is to evaluate the effects of physical therapy on temporal summation (TS) and conditioned pain modulation (CPM) in patients with chronic musculoskeletal pain. METHODS: This is a systematic review and meta-analysis. We searched the MEDLINE, EMBASE, CINAHL, EBSCO, PubMed, PEDro, Cochrane Collaboration Trials Register, Cochrane Database of Systematic Reviews, and SCOPUS databases. Different mesh terms and key words were combined for the search strategy, with the aim of encompassing all studies that have used any type of physical therapy treatment in patients with chronic musculoskeletal pain and have measured both TS and CPM. RESULTS: Eighteen studies remained for qualitative analysis and 16 for quantitative analysis. Statistically significant differences with a 95% confidence interval (CI) were obtained for TS (-0.21, 95% CI = -0.39 to -0.03, Z = 2.50, P = 0.02, N = 721) and CPM (0.34, 95% CI = 0.12 to 0.56, Z = 2.99, P = 0.003, N = 680) in favor of physical therapy as compared with control. Manual therapy produces a slight improvement in TS, and physical therapy modalities in general improve CPM. No significant differences between the subgroups of the meta-analysis were found. The methodological quality of the studies was high. CONCLUSIONS: Physical therapy produces a slight improvement in central sensitization (CS)-related variables, with TS decreased and CPM increased when compared with a control group in patients with CMP. Only significant differences in TS were identified in the manual therapy subgroup.