Unraveling the Mechanisms of Manual Therapy: Modeling an Approach PDF

[ clinical commentary ] JOEL E. BIALOSKY, PT, PhD1,2 JASON M. BENECIUK, PT, PhD1,2 MARK D. BISHOP, PT...

[ clinical commentary ] JOEL E. BIALOSKY, PT, PhD1,2 JASON M. BENECIUK, PT, PhD1,2 MARK D. BISHOP, PT, PhD1 ROGELIO A. CORONADO, PT, PhD3 CHARLES W. PENZA, DC, PhD1 COREY B. SIMON, PT, PhD4,5 STEVEN Z. GEORGE, PT, PhD5 Unraveling the Mechanisms of Manual Therapy: Modeling an Approach M anual therapy (MT) interventions are a preferred treatment these 2 prerequisites are met, patients can for both health care professionals from a variety of be matched to an appropriate treatment, disciplines14,36,77,82 and patients with musculoskeletal pain allowing for the targeted application Downloaded from www.jospt.org at on October 20, 2024. For personal use only. No other uses without permission. of a specific intervention of known conditions.2,12,53,70 Despite the popularity of MT, systematic mechanisms to patients with presentations reviews only find small to modest effect sizes43,73 or fail to recommend amenable to these mechanisms.15,45 these interventions.39,68 In fact, individual clinical practice guidelines Mechanistic-based treatment approaches for low back pain include differing recommendations for the use of for MT necessitate identification of the key spinal manipulation, indicating Mechanistic-based approaches mechanisms through which MT works; Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved. conflicting research support.60 Such to treating individuals presenting however, the current understanding of findings are not dissimilar to those for with musculoskeletal pain conditions these mechanisms is lacking, requiring other interventions for pain and are represent a rational targeted approach additional and more optimally designed attributed to substantial individual for personalizing treatment.26,32,45 studies to answer this important question. variability in treatment response. 32 There are 2 prerequisites needed to Subsequently, the clinical decision- properly implement this approach: The Need for a Model making process that guides the use first, a mechanism contributing to a of the Mechanisms of MT of MT may be best directed at the clinical population or subpopulation The mechanistic approach to MT is individual patient on the provider level, (ie, a homogeneous subgroup) must be complicated by the complex nature of Journal of Orthopaedic & Sports Physical Therapy® rather than using a “one-size-fits-all” identified; second, the biological effects of MT interventions. While drug effects are approach.32 a treatment should be established. When often attributed to a specific and well- defined active ingredient, the mechanisms UUSYNOPSIS: Manual therapy interventions are the patient, the provider, and the environment in underlying complex interventions, such as popular among individual health care providers which the intervention occurs. Therefore, a model those used for MT, are multifaceted and and their patients; however, systematic reviews to guide both study design and the interpreta- comprise specific and nonspecific factors do not strongly support their effectiveness. tion of findings is necessary. We have previously related to the intervention, the patient, the Small treatment effect sizes of manual therapy proposed a model suggesting that the mechanical provider, and the environment in which interventions may result from a “one-size-fits- all” approach to treatment. Mechanistic-based force from a manual therapy intervention results the intervention is provided. Subsequently, treatment approaches to manual therapy offer in systemic neurophysiological responses leading a single, well-defined mechanism of an an intriguing alternative for identifying patients to pain inhibition. In this clinical commentary, we MT intervention is unlikely, and resulting likely to respond to manual therapy. However, the provide a narrative appraisal of the model and outcomes are probably related to varying current lack of knowledge of the mechanisms recommendations to advance the study of manual inherent elements and contextual through which manual therapy interventions therapy mechanisms. J Orthop Sports Phys Ther factors.13,25,74 We believe that research inhibit pain limits such an approach. The nature of 2018;48(1):8-18. doi:10.2519/jospt.2018.7476 focusing on individual mechanisms manual therapy interventions further confounds such an approach, as the related mechanisms are UUKEY WORDS: manipulation, mobilization, in isolation will always fall short of likely a complex interaction of factors related to neurophysiology, pain, theory providing meaningful insight, because MT is a complex intervention involving 1 Department of Physical Therapy, University of Florida, Gainesville, FL. 2Brooks-PHHP Research Collaboration, Jacksonville, FL. 3Department of Physical Therapy and Department of Orthopaedic Surgery and Rehabilitation, University of Texas Medical Branch, Galveston, TX. 4Doctor of Physical Therapy Program, Duke University, Durham, NC. 5Duke Clinical Research Institute and Department of Orthopaedic Surgery, Duke University, Durham, NC. Drs Bialosky and Bishop were supported by National Center for Complementary and Integrative Health grant R01 AT006334 from the National Institutes of Health. The authors certify that they have no affiliations with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the article. Address correspondence to Dr Joel E. Bialosky, Department of Physical Therapy, University of Florida, Box 100154, University of Florida Health Science Center, Gainesville, FL 32610-0154. E-mail: [email protected] t Copyright ©2018 Journal of Orthopaedic & Sports Physical Therapy® 8 | january 2018 | volume 48 | number 1 | journal of orthopaedic & sports physical therapy  multiple interactions of complementary and not intended to emphasize any tic literature within the context of our mechanisms. As with other complex single or specific approach. The model model, as well as highlight key areas for interventions, MT providers and was designed to comprehensively account advancing this area of research. For the researchers benefit from a theoretical for the interacting mechanisms behind a model to continue to be relevant, specific model to both guide the design and assist complex MT intervention. Importantly, issues related to its future application in interpreting the results of mechanistic the model allows researchers (1) to are considered. Importantly, this com- studies. consider and account for competing mentary is not intended to be a system- We published a model to begin to mechanisms when designing studies (ie, atic review or complete appraisal of the account for the multiple pain inhibitory mechanisms related to biomechanical original model. Rather, the commentary mechanisms of MT.6 The model postulates effects, peripherally mediated effects, highlights areas that we believe are im- that the mechanical stimulus from an MT spinal cord–mediated effects, and portant considerations for progressing intervention results in neurophysiological supraspinally mediated effects), and clinical and research perspectives. responses within the peripheral and (2) to acknowledge the potential for Downloaded from www.jospt.org at on October 20, 2024. For personal use only. No other uses without permission. central nervous systems responsible for alternative plausible explanations to their Advancing the Understanding Through pain inhibition (FIGURE 1). Importantly, findings should the study not account for Appropriate Study Design the model is applicable to different competing mechanisms. Mechanistic studies of MT are often per- MT approaches (ie, joint mobilization, This clinical commentary will address formed in humans, which, unlike animal massage, neurodynamic interventions) the current state of the MT mechanis- models, prohibit direct observation of the Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved. Imaging Nonspecific responses Placebo/expectation Psychological measures Pain modulatory - Fear circuitry - Catastrophizing Pain Pain-related ACC - Kinesiophobia brain circuitry Amygdala PAG Endocrine response Journal of Orthopaedic & Sports Physical Therapy® RVM Rating B-endorphins Opioid response Imaging Autonomic response Skin temperature Skin conduction Cortisol levels Heart rate Mechanical stimulus Tissue Peripheral nervous system Spinal cord Neuromuscular responses Motoneuron pool Afferent discharge Muscle activity Decrease spasm Increase range of motion Hypoalgesia Inflammatory mediators Temporal summation Selective blocking of neurotransmitters Imaging FIGURE 1. Comprehensive model of the mechanisms of manual therapy. The model suggests that a transient, mechanical stimulus to the tissue produces a chain of neurophysiological effects. Solid arrows denote a direct mediating effect. Broken arrows denote an associative relationship, which may include an association between a construct and its measure. Bold boxes indicate the measurement of a construct. Abbreviations: ACC, anterior cingulate cortex; PAG, periaqueductal gray; RVM, rostral ventromedial medulla. Reprinted from Bialosky et al,6 with permission from Elsevier. ©2009 Elsevier. journal of orthopaedic & sports physical therapy | volume 48 | number 1 | january 2018 | 9  [ clinical commentary ] nervous system. Our model based the as- temporal precedence with an outcome. since the model was originally published, sessment of nervous system responses to For example, spinal stiffness and lumbar and, in fact, more recent studies continue MT in humans on associated responses multifidus recruitment were assessed at to refute a specific biomechanical mech- serving as behavioral correlates (ie, proxy baseline and immediately following a anism. The clinical examination process measures) of underlying mechanisms. spinal manipulative therapy intervention for determining biomechanical dysfunc- For example, changes in skin blood flow over 2 sessions, and then a week follow- tion continues to be unreliable,97 relates represent an indirect correlate of the ing the second session, in participants poorly to clinical outcomes,85 and dem- sympathetic nervous system responses with low back pain.38 Improvements in onstrates a poor association with reli- to MT,104 while changes in the flexor the Oswestry Disability Index were me- able and accurate mechanical measures61 withdrawal reflex may represent a spinal diated by improved lumbar multifidus as well as with magnetic resonance cord–mediated response to MT.24 Nu- recruitment and decreases in stiffness.38 imaging.63 merous studies have provided evidence of Moderators are variables measured prior Specific to clinical outcomes, signifi- immediate neurophysiological responses to treatment that interact with a specific cant within-group improvements are ob- Downloaded from www.jospt.org at on October 20, 2024. For personal use only. No other uses without permission. following MT; however, while serving intervention and influence an outcome of served in response to MT interventions; as proof-of-concept work for more com- interest often identified in a randomized however, between-group differences are plex designs, single pre/post randomized clinical trial.62,76 For example, secondary not observed, confirming similar re- controlled trials are not designed to de- analysis of the UK BEAM trial found sponses to techniques of varying mechan- termine the individual or combined in- that, although several baseline factors ical parameters.19,55,100 Furthermore, the fluential factors of clinical improvement. predicted overall outcome, none were clinical outcomes of MT interventions, Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved. Future studies must establish a link be- predictive of response to a specific treat- whether based on clinical presentation tween these associated responses and ment (ie, spinal manipulation, exercise, or random allocation, are similar.31,59 Col- clinical symptoms, as well as establish or spinal manipulation followed by exer- lectively, this body of literature continues covariance of improvements between as- cise), with only trends identified for the to support our initial assertion against an sociated responses and clinical outcomes. role of positive treatment expectations isolated and specific mechanical mecha- Evaluating these multifactorial relation- for those receiving combined treatment.93 nism accounting for clinical outcomes in ships requires complex study designs Identifying treatment-effect moderators response to complex MT interventions.6 that are not always feasible to conduct in provides information to establish “for Despite this evidence to the contrary, clinical settings. Cook18 has highlighted whom and under what conditions” treat- the clinical approach to MT based on a Journal of Orthopaedic & Sports Physical Therapy® the limitations of reliance on immediate ment is effective.76 theorized specific biomechanical mecha- assessment of either mechanistic or clini- nism persists.1,29,30,42,95 We believe that cal outcomes, including similar findings Advancing the Understanding this perpetuation of dated modes of ac- in response to numerous interventions of the Mechanical Force tion for MT is both unsubstantiated and and the failure to relate these to long- Clinical use of MT is traditionally driven counterproductive. term clinical outcomes. One strategy to by the assumption of a peripherally act- address these concerns and to advance ing, mechanical mechanism,10,33,52 for ex- Advancing the Understanding this line of research in future studies is to ample, the application of a specific MT of MT-Related Pain Inhibition attempt to distinguish these immediate technique applied to a perceived dys- Our model was designed to account associated responses as treatment me- functional vertebral segment identified for the mechanism of MT on pain diators and moderators. Mediators are through passive movement assessment inhibition.6 Psychophysical testing, variables measured during the course or imaging. Our model acknowledges a such as the application of standardized of treatment to evaluate for change and mechanical force as an inherent element noxious thermal or mechanical forces, subsequent impact on outcome.62,76 Me- of any MT intervention and directs stud- allows for the study of mechanisms diators have been described as process ies to account for mechanical force as a related to changes in pain processing. variables that implicate possible mecha- potential contributing mechanism. Based Systematic reviews support a transient nisms by which an intervention may be on the literature at the time, the model pain inhibitory effect of MT21,40,69 on effective, especially when these variables theorized that clinical outcomes were re- psychophysical measures, occurring represent a plausible construct that the lated to corresponding neurophysiologi- both locally and remotely. Higher pain treatment is intended to modify. Potential cal responses and occurred independent sensitivity, as determined by a lower pain mediators of change establish how or why of the specific mechanical parameters of threshold at the site of injury or pain, may treatment effects occur and should be the force. Little has changed to support a reflect local sensitization in the peripheral identified a priori and measured before, mechanism related to the specific biome- (reduced receptor threshold) or central during, and after treatment to establish chanical parameters of the interventions nervous system (specific somatosensory 10 | january 2018 | volume 48 | number 1 | journal of orthopaedic & sports physical therapy  regions), while higher pain sensitivity at shown that temporal summation of transcutaneous electrical nerve stimu- sites distant from the site of injury may heat pain is reduced immediately after lation has incorporated paradigms that reflect more general sensitization of the the application of spinal manipulative determine differential pain-relieving central nervous system. Changes in pain therapy, and that these reductions effects on movement-evoked pain.83,94 sensitivity are observed in response to are greater than those following Movement-evoked pain lessens following MT both at the site of application and exercise or carefully constructed sham an MT intervention,4,56,57 which suggests at distal sites, indicating the presence interventions. 7-9,11 Improved pain that future investigation should differ- of a central mediating effect.22,64,81 The modulatory capacity, as observed through entiate these findings from spontaneous approach of such studies is often limited changes in conditioned pain modulation, pain, in terms of the magnitude of re- to assessment of static measures of has been found to correspond to sponse as well as the relationship to clini- mechanical and thermal pain thresholds, joint mobilization to the knee in cal outcomes of importance to patients. providing little insight into individual participants with knee osteoarthritis.23 pain modulation capacity. Subsequently, favorable changes in Advancing the Understanding of Downloaded from www.jospt.org at on October 20, 2024. For personal use only. No other uses without permission. Psychophysical testing protocols pain modulatory capacity represent a Supraspinally Mediated Mechanisms allow for the assessment of in vivo pain potential biological effect of MT, possibly Previous mechanistic models of MT modulatory capacities and profiling informing mechanistic-based treatment incorporating nervous system responses of individuals based on response approaches. Such approaches have been took a “reflexive” route, meaning that to nociceptive input. For example, undertaken in drug trials. For example, neurological responses to MT were conditioned pain modulation is duloxetine, a drug that enhances limited to physiologic or autonomic Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved. characterized by a reduction of pain descending inhibition of pain, is more outputs.75 Our model acknowledged sensitivity at one site in response effective in individuals who demonstrate such processes but advanced the pathway to nociceptive input at another site diminished conditioned pain into regions of the nervous system not and reflects descending inhibition of modulation.103 Furthermore, ketamine, typically considered as having a “direct” pain through the spino-bulbar-spinal which inhibits temporal summation, is response to MT. The timing of this focus loop, representing a pain inhibitory more effective for individuals presenting was vital, because when the model was process. 78,101 Temporal summation, with heightened temporal summation.46 first proposed, limited evidence from characterized by an increase in pain A similar approach has not been human and animal research supported sensitivity in response to repeated adequately considered in the field of MT, the assumption of MT altering sensory Journal of Orthopaedic & Sports Physical Therapy® noxious stimulation, represents increased necessitating further study and a future processing in supraspinal structures.48,65,84 dorsal horn excitability27,47 and reflects a direction of studies of pain inhibition in The understanding of supraspinally pain facilitatory process.45,102 Dynamic response to MT. mediated mechanisms of MT has pro- psychophysical testing allows for profiling Movement-evoked pain offers an gressed greatly since the model was of individuals. For example, those with alternative pain modulatory measure originally published, including studies augmented temporal summation or that should be considered in future of MT-associated measures of cortical inefficient conditioned pain modulation mechanistic-focused MT studies. Move- function through somatosensory-evoked are considered at risk for developing ment-evoked pain often has a greater as- potentials,48,49 as well as neuroimaging a pain condition, experiencing greater sociation with physical function decline advances through positron emission pain severity when a pain condition and decreased quality of life than does tomography72 and functional magnetic develops, and progressing from acute resting/spontaneous pain.87,89 For exam- resonance imaging (fMRI). Findings pain to chronic pain.102 Conversely, those ple, pain in response to a repeated lifting from these approaches have significantly with blunted temporal summation or task accounted for significant and unique advanced the understanding of MT- augmented conditioned pain modulation variance in disability beyond a measure related changes in cortical function. For may be less likely to develop a pain of spontaneous pain in participants with example, fMRI has been used to study the condition, experience less pain severity whiplash-associated disorder.66 Differ- effects of MT in several complementary when a pain condition develops, and ences in magnitude and influence of pain ways. First, fMRI has been used to inves- be less likely to progress from acute types suggest that different mechanisms tigate cortical responses during MT. For to chronic pain.102 Subsequently, pain and MT effects may also differ between example, during the posterior-to-anterior modulatory profiles may be useful in spontaneous and movement-evoked mechanical force produced by MT, acti- identifying more homogeneous groups pain. Considering movement-evoked vation is observed in medial parts of the of patients. pain may better characterize the pain- postcentral gyrus (S1) bilaterally, the sec- Pain modulatory capacities are relieving properties of interventions pro- ondary somatosensory cortex (S2), poste- responsive to MT. For example, we have viding episodic relief. The literature on rior parts of the insular cortex, different journal of orthopaedic & sports physical therapy | volume 48 | number 1 | january 2018 | 11  [ clinical commentary ] Zone 1 Zone 2 Zone 3 Provider Mechanical stimulus Pain modulatory Pain-related Clinical circuitry Pain inhibition Downloaded from www.jospt.org at on October 20, 2024. For personal use only. No other uses without permission. brain circuitry outcomes Context Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved. Tissue Peripheral nervous system Spinal cord Patient FIGURE 2. Updated comprehensive model of the mechanisms of manual therapy. The model suggests that a transient, mechanical stimulus to the tissue produces a chain of neurophysiological effects. Zone 1 represents the mechanical stimulus from the provider to the tissue, as well as the interaction between the patient and provider. Zone 2 Journal of Orthopaedic & Sports Physical Therapy® represents potential nervous system responses to the mechanical stimulus, as well as the patient-provider interaction. Zone 3 represents the potential outcomes. parts of the cingulate cortex, and the cer- ing of nociception before and after MT. results of this study suggest that MT al- ebellum.67 Second, fMRI has been used to Healthy volunteers, who completed an ters cortical interactions within nocicep- assess how MT alters the central nervous exercise-injury protocol to induce low tive processing networks at rest, such that system responses to a noxious stimulus. back pain, underwent resting-state fMRI. subsequent stimuli are received within For example, healthy volunteers under- They were then randomized into 1 of 3 the cortex in an altered state. Future went fMRI scanning while receiving nox- MT interventions: spinal thrust manipu- studies should attempt to further clarify ious stimuli applied to the cuticle of the lation, spinal nonthrust mobilization, or how MT disrupts maladaptive cortical index finger. Participants then received therapeutic touch, and then underwent patterns and functional connectivity as- a supine thrust manipulation directed a second resting-state fMRI. Following sociated with chronic pain. to the mid thoracic spine and were im- MT, there was a reduction in experimen- mediately returned to the scanner for re- tally induced low back pain, with no dif- Limitations imaging with a second delivery of noxious ferences observed between types of MT. Methodological approaches to stimuli. The thrust joint manipulation Common to all MT interventions, the measurement are one of the primary was associated with hypoalgesia, as well coupling of cortical activity decreased be- limitations to the study of MT as a significant reduction in activity in the tween sensory discriminant and affective mechanisms, as many techniques sensory-motor cortices S1, S2, anterior regions (primary somatosensory cortex described in the model to evaluate cingulate cortex, cerebellum, and insular and posterior insular cortex), while in- nervous system processing are not cortices, with reduction of cortical activ- creases were observed between affective direct or are isolated measures of ity correlated to decreased pain percep- regions (posterior cingulate and anterior nervous system activity. The model is tion.86 Third, resting-state fMRI assessed insular cortices) and affective and de- based on associated neurophysiological the coupling of cortical activity between scending pain modulatory regions (insu- responses and not direct observation of brain regions involved in the process- lar cortex and periaqueductal gray).41 The nervous system activity. Subsequently, 12 | january 2018 | volume 48 | number 1 | journal of orthopaedic & sports physical therapy  have been associated with clinical out- Equipoise comes. For example, a study comparing Expectation Provider the use of spinal thrust manipulation to Pain beliefs Clinical experience nonthrust mobilization for participants Mechanical stimulus with low back pain observed no group- Soft tissue biased dependent differences in pain, disability, Nerve biased total visits, days in care, or rate of recov- Joint biased ery; however, a significant association was observed between the treating therapist’s lack of equipoise (ie, preference for thrust versus nonthrust mobilization) and sub- Context sequent outcomes.19 Moreover, provider expectations can also influence patient Downloaded from www.jospt.org at on October 20, 2024. For personal use only. No other uses without permission. outcomes. For example, baseline physician expectations are predictive of changes in pain and physical function in response to acupuncture in individuals with chronic pain99 and in return to work following an Stiffness acute episode of low back pain.58 Further- Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved. Tissue Muscle tone Preference Range of motion more, pain relief in response to a placebo Expectation intervention was significantly greater for Pain beliefs Patient Pain-associated distress a group of individuals following third mo- Prior experience lar surgery when the provider was aware of the chance of administering an active FIGURE 3. Zone 1 of the model, encompassing the interaction between the provider and patient, as well as the medication, as compared to when the mechanical stimulus to the targeted tissue. Solid arrows denote a direct mediating effect. Broken arrows denote provider knew that no active drug would an association between a construct and its measure. Bold boxes provide examples of measurable constructs for be administered.44 Collectively, provider consideration. preference and expectations have strong Journal of Orthopaedic & Sports Physical Therapy® potential to influence MT outcomes; the observed responses are suggestive replacement for determining clinically therefore, we have revised the model to of specific nervous system activity effective interventions. account for both the potential role of pro- (generally based on findings from animal vider characteristics in the mechanical studies); however, these assumptions are Advancing the Model force, as well as the potential influence on not directly confirmable in humans, as We have modified the model since its ini- patient-reported outcomes through a su- conducting such studies would introduce tial development to represent some of the praspinally mediated effect. valid ethical concerns. The model key changes in understanding MT mecha- Finally, the model was designed to considers associated neurophysiological nisms. For simplicity, we present the re- account for the mechanisms of MT in pain responses and attempts to provide vised model in its entirety (FIGURE 2) and inhibition. However, complete reliance direct relationships to clinical outcomes. by individual zones, with zone 1 (FIGURE on this aspect of MT may result in limited Importantly, neurophysiological 3) representing the provider, mechanical conclusions and failure to acknowledge responses to MT are beneficial in force, and targeted tissue; zone 2 (FIGURE overall clinical effectiveness, which is furthering our understanding of why 4) representing patient nervous system yet another multifactorial construct. MT is effective; however, the gold responses; and zone 3 (FIGURE 5) repre- More recently, reliance on the sensory standard for determining whether senting clinical outcomes. The personal aspect of pain as a primary outcome MT is effective is patient self-report.80 attributes of the MT provider (ie, the clini- has been discouraged in the case of The model can be used to guide and cian) comprise one element omitted from chronic pain conditions.90 Core outcome account for nervous system responses the original model. Clinical equipoise is domains for pain have been suggested, to MT as a plausible explanation for the lack of a preference for an interven- including factors such as physical observed clinical outcomes; however, tion. Equipoise is desirable in clinical function, emotional function, sleep, and neurophysiological responses must be trials to avoid bias20; however, a lack of satisfaction with treatment.91,92 Patients linked to patient self-report outcomes equipoise may be desirable in practice, as seeking physical therapy care attach and should not be interpreted as a provider preferences for an intervention importance to improvement in constructs journal of orthopaedic & sports physical therapy | volume 48 | number 1 | january 2018 | 13  [ clinical commentary ] domains that are valued from a patient Somatosensory-evoked Somatosensory-evoked perspective. potentials potentials Imaging Imaging – Positron emission – Positron emission CONCLUSION tomography tomography T – Functional magnetic – Functional magnetic he implementation of effective resonance imaging resonance imaging Conditioned pain MT depends on many factors, in- modulation cluding a thorough understanding of the underlying multifactorial mecha- nisms through which these interventions exert their effectiveness. Determin- ing the mechanisms of MT would both Pain modulatory Pain-related strengthen the best available research Downloaded from www.jospt.org at on October 20, 2024. For personal use only. No other uses without permission. circuitry brain circuitry and enhance clinical practice through a personalized treatment approach, perhaps resulting in better agreement between clinical judgment, patient pref- Autonomic response erences, and the available literature. Clin- – Skin temperature ical prediction rules are one approach to Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. All rights reserved. – Skin conduction – Cortisol levels stratification initially embraced by MT – Heart rate providers and researchers. Many clini- Peripheral nervous system Spinal cord Neuromuscular cal prediction rules purported to identify responses – Motoneuron pool key signs and symptoms suggestive of pa- – Afferent discharge tients with musculoskeletal pain who are – Muscle activity likely to benefit from MT.3,16,28,34,37,54,71,79,96 Temporal summation Despite the initial enthusiasm, the meth- Cytokines odology of these approaches has been Neuropeptides questioned and cautious interpretation Journal of Orthopaedic & Sports Physical Therapy® Nerve growth factor recommended, as initial results may rep- resent spurious findings or a generally fa- FIGURE 4. Zone 2 of the model, encompassing the nervous system response of the patient to receiving a manual vorable prognosis rather than one specific therapy intervention. Solid arrows denote a direct mediating effect. Broken arrows denote an association between a construct and its measure. Bold boxes provide examples of measurable associated responses suggestive of a to the effects of MT.5,51,88 Furthermore, direct nervous system response. derivation studies require validation, and the vast majority of derived clinical prediction rules lack additional study or Movement-evoked pain Pain inhibition Clinical outcomes have failed attempted validation stud- Resting pain Emotional distress ies.17,35,50 While a noble effort, the current Fatigue state of clinical prediction rules suggests Interference that this approach may not be optimal for Satisfaction Decreased pain sensitivity identifying MT responders. Subsequent- Enhanced pain inhibition ly, a different approach is necessary, and Decreased pain facilitation mechanistic-based approaches may pro- vide a more robust method. FIGURE 5. Zone 3 of the model, encompassing the outcomes of the model for which related mechanisms of Study of the mechanisms of MT is manual therapy may account. Solid arrows denote a direct mediating effect. Broken arrows denote an association between a construct and its measure. Bold boxes provide examples of measurable constructs for consideration. made difficult by the complex nature of these interventions, resulting in the in- beyond the sensory aspect of pain,105 and domains are not mechanistic, precluding teraction of multiple complementary MT is effective in altering outcomes a similar approach to study; and (2) pain mechanisms. We have published a model beyond the sensory aspect of pain.53,98 We inhibition is an important precursor to that served as the basis for studies to believe that a continued emphasis of the the other domains. However, mechanistic further our understanding of aspects of model of the mechanisms of MT in pain studies should be designed to link MT- modulation of pain sensitivity, as well as inhibition is warranted, because (1) other related pain inhibition to core outcome to guide studies of supraspinal effects of 14 | january 2018 | volume 48 | number 1 | journal of orthopaedic & sports physical therapy  MT. Recent work suggests limitations to comprehensive model. Man Ther. 2009;14:531- a general cervical range of motion exercise: the original model that can be improved 538. https://doi.org/10.1016/j.math.2008.09.001 multi-center randomized clinical trial. Phys Ther. by the inclusion of provider factors, the 7. B  ialosky JE, Bishop MD, Price DD, Robinson ME, 2010;90:1239-1250. https://doi.org/10.2522/ Vincent KR, George SZ. A randomized sham- ptj.20100123 inclusion of movement-evoked pain, and controlled trial of a neurodynamic technique 18. Cook C. Immediate effects from manual therapy: linking findings to a broader spectrum in the treatment of carpal tunnel syndrome. J