An overview of systematic reviews examining the quantitative sensory testing-derived hypoalgesic effects of manual therapy for musculoskeletal pain.

BACKGROUND: Changes in quantitative sensory testing (QST) after manual therapy can provide insight into pain relief mechanisms. Prior systematic reviews have evaluated manual-therapy-induced QST change. This overview of systematic reviews aims to consolidate this body of literature and critically review evidence on the hypoalgesic effects of manual therapy in clinical populations. METHODS: A comprehensive search was conducted on PubMed, CINAHL, PsycInfo, and Embase. Peer-reviewed systematic reviews with or without meta-analysis were eligible if the reviews examined the effect of manual therapy compared to non-manual therapy interventions on QST outcomes in clinical populations. Methodological quality was assessed with the AMSTAR 2 tool. Meta-analysis results and qualitative (non-meta-analysis) interpretations were summarized by type of manual therapy. Overlap of studies was examined with the corrected covered area (CCA) index. RESULTS: Thirty systematic reviews, including 11 meta-analyses, met inclusion. There was a slight overlap in studies (CCA of 1.72% for all reviews and 1.69% for meta-analyses). Methodological quality was predominantly low to critically low. Eight (27%) reviews examined studies with a range of manual therapy types, 13 (43%) reviews focused on joint-biased manual therapy, 7 (23%) reviews focused on muscle-biased manual therapy, and 2 (7%) reviews focused on nerve-biased manual therapy. Twenty-nine (97%) reviews reported on pressure pain threshold (PPT). Meta-analytic results demonstrated conflicting evidence that manual therapy results in greater hypoalgesic effects compared to other interventions or controls. CONCLUSION: Our overview of QST effects, which has relevance to mechanisms underlying hypoalgesia, shows conflicting evidence from mostly low to critically low systematic reviews.

Expectations affect pain sensitivity changes during massage.

BACKGROUND: Pain-inducing massage produces comparable changes in pain sensitivity as a cold pressor task, suggesting shared neurophysiological mechanisms of conditioned pain modulation. Manual therapy and conditioned pain modulation are influenced by positive and negative expectations. Therefore, the purpose of this study was to examine the effects of positive and negative expectations on pain-free and pain-inducing massage. METHODS: 56 healthy participants were randomly assigned to receive a positive or negative expectation instructional set followed by a pain-inducing or a pain-free massage. Pressure pain threshold (PPT) was measured followed by each interval of massage. A repeated measures ANCOVA controlling for post-randomization differences in sex tested for massage x expectation set x PPT interaction effects, as well as two-way interaction effects. RESULTS: A significant three-way interaction effect (p = 0.04) and time x expectation interaction effect was observed for individuals receiving pain inducing massage (p = 0.02). Individuals who received the positive expectation instructional set demonstrated significantly higher PPT at minutes 3 and 4 of massage compared to individuals who received the negative expectation instructional set. CONCLUSIONS: Expectations impact pain sensitivity changes produced during massage. Clinicians planning to provide pain-inducing massage should consider the role of expectations in modulating pain sensitivity changes.

A psychophysical study comparing massage to conditioned pain modulation: A single blind randomized controlled trial in healthy participants.

INTRODUCTION: Pain-inducing massage results in greater pain inhibition than pain free massage, suggesting a mechanism dependent on conditioned pain modulation (CPM). The purpose of this study was to test the hypothesis that pain inducing massage produces similar magnitude of reduction in pain sensitivity as a cold pressor task and that baseline conditioned pain modulation efficiency predicts pain inducing massage related hypoalgesia. METHODS: Sixty healthy participants were randomly assigned to receive either pain inducing massage to the neck, cold pressor task to the hand, or pain free massage to the neck. Participants also underwent pre and immediate post-intervention quantitative sensory testing. A repeated measures ANCOVA determined between group differences in pain sensitivity changes. RESULTS: Pain inducing massage used as a conditioning stimulus resulted in comparable experimental pain sensitivity changes as a cold pressor task (p > 0.05). Pain intensity during the intervention demonstrated a weak correlation (r = 0.20, p = 0.12) with changes in pain sensitivity at a remote site. Individuals with an efficient CPM at baseline who received the pain inducing massage displayed greater increases in pressure pain threshold compared to individuals with a less efficient CPM indicating the potential benefit of treatment stratification by mechanism. CONCLUSION: Although pain inducing massage resulted in less self-reported pain than a cold pressor task, both resulted in similar magnitude of the CPM response, suggesting shared underlying mechanisms. Understanding mechanisms of interventions can move us closer to mechanistic based treatments for pain which is consistent with a personalized medicine approach to care.

Unraveling the Mechanisms of Manual Therapy: Modeling an Approach.

Synopsis Manual therapy interventions are popular among individual health care providers and their patients; however, systematic reviews do not strongly support their effectiveness. Small treatment effect sizes of manual therapy interventions may result from a "one-size-fits-all" approach to treatment. Mechanistic-based treatment approaches to manual therapy offer an intriguing alternative for identifying patients likely to respond to manual therapy. However, the current lack of knowledge of the mechanisms through which manual therapy interventions inhibit pain limits such an approach. The nature of manual therapy interventions further confounds such an approach, as the related mechanisms are likely a complex interaction of factors related to the patient, the provider, and the environment in which the intervention occurs. Therefore, a model to guide both study design and the interpretation of findings is necessary. We have previously proposed a model suggesting that the mechanical force from a manual therapy intervention results in systemic neurophysiological responses leading to pain inhibition. In this clinical commentary, we provide a narrative appraisal of the model and recommendations to advance the study of manual therapy mechanisms. J Orthop Sports Phys Ther 2018;48(1):8-18. doi:10.2519/jospt.2018.7476.

Placebo Mechanisms of Manual Therapy: A Sheep in Wolf's Clothing?

When a physical therapist provides a manual therapy (MT) intervention for a patient presenting with pain and the patient experiences a positive clinical outcome, we cannot answer as to why this occurs. Would we continue to devote valuable time and financial resources to learning and improving our skills in providing MT interventions if the related clinical outcomes were placebo responses? In this Viewpoint, the authors conceptualize placebo as an active and important mechanism of MT and argue that placebo mechanisms deserve consideration as an important component of the treatment effect. J Orthop Sports Phys Ther 2017;47(5):301-304. doi:10.2519/jospt.2017.0604.

Spinal manipulative therapy-specific changes in pain sensitivity in individuals with low back pain (NCT01168999).

UNLABELLED: Spinal manipulative therapy (SMT) is effective for some individuals experiencing low back pain; however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity, suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity, and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with low back pain to receive SMT, placebo SMT, placebo SMT with the instructional set "The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people," or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over 2 weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following 2 weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (P = .05, partial η(2) = .07). Group-dependent differences were not observed for changes in pain intensity and disability at 2 weeks. Participant satisfaction was greatest following the enhanced placebo SMT. This study was registered at www.clinicaltrials.gov under the identifier NCT01168999. PERSPECTIVE: The results of this study indicate attenuation of pain sensitivity is greater in response to SMT than the expectation of receiving an SMT. These findings suggest a potential mechanism of SMT related to lessening of central sensitization and may indicate a preclinical effect beyond the expectations of receiving SMT.

Basis for spinal manipulative therapy: a physical therapist perspective.

Physical therapists internationally provide spinal manipulative therapy (SMT) to patients with musculoskeletal pain complaints. SMT has been a part of physical therapist practice since the profession's beginning. Early physical therapist clinical decision making for SMT was influenced by the approaches of osteopathic and orthopedic physicians at the time. Currently a segmental clinical decision making approach and a responder clinical decision making approach are two of the more common models through which physical therapist clinical use of SMT is directed. The focus of segmental clinical decision making is upon identifying a dysfunctional vertebral segment with the application of SMT to restore mobility and/or alleviate pain. The responder clinical decision making approach attempts to categorize individuals based on a pattern of signs and symptoms suggesting a likely positive response to SMT. The present manuscript provides an overview of common physical therapist clinical decision making approaches to SMT and presents areas requiring further study in order to optimize patient response.

Heightened pain sensitivity in individuals with signs and symptoms of carpal tunnel syndrome and the relationship to clinical outcomes following a manual therapy intervention.

Neurophysiological responses related to lessening of pain sensitivity are a suggested mechanism of manual therapy. Prior studies have observed generalized lower pain thresholds associated with carpal tunnel syndrome (CTS) in comparison to healthy controls. The present study sought to determine whether similar findings were present in suprathreshold measures and measures specific to central integration of pain (temporal summation and after sensations). Additionally, we wished to determine whether measures of pain sensitivity were related to clinical outcomes in participants with signs and symptoms of CTS receiving a manual therapy intervention. Individuals with signs and symptoms of CTS reported greater pain sensitivity to suprathreshold measures of mechanical pain, temporal summation, and after sensation in comparison to healthy controls. Immediate lessening of mechanical pain sensitivity and after sensations in response to a manual therapy intervention and 3-week attenuation of temporal summation following a 3-week course of manual therapy were associated with 3-week changes in clinical pain intensity in participants with signs and symptoms of CTS. These findings suggest heightened pain sensitivity across several parameters may be associated with CTS. Furthermore, changes in mechanical pain, after sensation, and temporal summation may be related to improvements in clinical outcomes.

The relationship of the audible pop to hypoalgesia associated with high-velocity, low-amplitude thrust manipulation: a secondary analysis of an experimental study in pain-free participants.

OBJECTIVE: High-velocity, low-amplitude (HVLA) manipulation is an effective treatment of low back pain (LBP); however, the corresponding mechanisms are undetermined. Hypoalgesia is associated with HVLA manipulation and suggests specific mechanisms of action. An audible pop (AP) is also associated with HVLA manipulation; however, the influence of the AP on the hypoalgesia associated with HVLA manipulation is not established. The purpose of the current study was to observe the influence of the AP on hypoalgesia associated with HVLA manipulation. METHODS: The current study represents a secondary analysis of 40 participants. All participants underwent thermal pain sensitivity testing to their leg and low back using protocols specific to A delta fiber-mediated pain and temporal summation. Next, participants received HVLA manipulation to their low back, and the examiner recorded whether an AP was perceived. Finally, participants underwent immediate follow-up thermal pain sensitivity testing using the same protocols. Separate repeated-measure analyses of variance (ANOVAs) were used to observe changes in pain sensitivity before and immediately after HVLA manipulation. RESULTS: Hypoalgesia of A delta fiber-mediated pain was observed in the low back after HVLA (P < .05), and this was independent of whether an AP was perceived (P > .05). Hypoalgesia of temporal summation was observed in the lower extremity after HVLA (P < .05), and this was independent of whether an AP was perceived (P = .08). However, a moderate effect size for temporal summation was observed favoring participants in whom an AP was perceived. CONCLUSION: The current study suggests hypoalgesia is associated with HVLA manipulation and occurs independently of a perceived AP. Inhibition of lower extremity temporal summation may be larger in individuals in whom an AP is perceived, but further study is necessary to confirm this finding.

A randomized sham-controlled trial of a neurodynamic technique in the treatment of carpal tunnel syndrome.

STUDY DESIGN: Randomized, controlled trial. OBJECTIVES: To assess the believability of a novel sham intervention for a neurodynamic technique (NDT) in participants with signs and symptoms of carpal tunnel syndrome (CTS). Additionally, we wished to assess a potential mechanism of NDT (hypoalgesia) and to compare outcomes related to clinical pain and upper extremity disability between NDT and a sham intervention. BACKGROUND: Preliminary evidence suggests that NDT is effective in the treatment of CTS. A sham-controlled study is lacking from the literature and could provide insight to the efficacy of NDT, as well as the corresponding mechanisms. METHODS: Participants with signs and symptoms consistent with CTS provided baseline measures of expectation, clinical pain intensity, upper extremity disability, and experimental pain sensitivity. Participants were then randomly assigned to receive either a NDT known to anatomically stress the median nerve or a sham technique intended to minimize stress to the median nerve. Following brief exposure to the assigned technique, expectation was reassessed to observe for group-dependent changes. Participants received the assigned intervention over 3 weeks. Additionally, all participants received a prefabricated wrist splint for their involved hands, with instructions to sleep in the splint and to wear it during painful activities when awake. Following 3 weeks of the assigned intervention and splint wear, baseline measures were reassessed and participants were asked which intervention they believed they had received. RESULTS: Forty females agreed to participate. Expectations for pain relief and perceived group assignment were similar between the groups. Within-session decreases in clinical pain intensity and pressure pain sensitivity were observed independent of group assignment. Reduction of temporal summation was observed only in participants receiving NDT. Significant improvements in clinical pain intensity and upper extremity disability were observed at 3 weeks, independent of group assignment. CONCLUSION: The sham intervention was successful in blinding the participants. Immediate changes in pain sensitivity and intensity and 3-week changes in clinical pain intensity and upper extremity disability associated with NDT were equivalent to a sham intervention to which the participants were adequately blinded. Conversely, reduction of temporal summation was only observed in participants receiving the NDT, suggesting the potential of a favorable neurophysiological effect.

The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model.

Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms.