Daniel S. Harvie

A systematic review of randomized controlled trials on exercise parameters in the treatment of patellofemoral pain: what works?

Purpose There is research evidence which supports the effectiveness of exercise in reducing pain and increasing function in patients with patellofemoral pain syndrome. However, what is unclear are the parameters underpinning this intervention. This has led to uncertainty when operationalizing exercises for patients with patellofemoral pain syndrome in clinical practice. The aim of this review was to evaluate the parameters of exercise programs reported in primary research, to provide clinicians with evidence-based recommendations for exercise prescription for patellofemoral pain. Methods A systematic review of randomized controlled trials was undertaken. Only trials that identified exercise to be effective in treating patellofemoral pain were included. Appropriate databases and reference lists were searched using established keywords. Data relating to common exercise parameters such as the type of exercise, length, and frequency of intervention, intensity, repetitions, sets, and specific technique were extracted, along with details of co-interventions that may have been used. Results A total of ten randomized controlled trials were included in this review and from these trials 14 interventions arms were evaluated. All 14 interventions focused on active exercises, all but two of which also included a passive stretching component. The current body of evidence demonstrates positive results with exercise interventions such as knee extension, squats, stationary cycling, static quadriceps, active straight leg raise, leg press, and step-up and down exercises for patients with patellofemoral pain syndrome. A progressive regime of daily exercises of two to four sets of ten or more repetitions over an intervention period of 6 weeks or more, combined with exercises to address flexibility of the lower limb musculature was commonly used. Conclusion Currently, the primary research on this topic supports the use of closed kinetic chain, strengthening exercises for musculature of the lower limb, combined with flexibility options. The current evidence base supports a prescription of daily exercises of two–four sets of ten or more repetitions over a period of 6 weeks or more.

Bogus Visual Feedback Alters Onset of Movement-Evoked Pain in People With Neck Pain

Pain is a protective perceptual response shaped by contextual, psychological, and sensory inputs that suggest danger to the body. Sensory cues suggesting that a body part is moving toward a painful position may credibly signal the threat and thereby modulate pain. In this experiment, we used virtual reality to investigate whether manipulating visual proprioceptive cues could alter movement-evoked pain in 24 people with neck pain. We hypothesized that pain would occur at a lesser degree of head rotation when visual feedback overstated true rotation and at a greater degree of rotation when visual feedback understated true rotation. Our hypothesis was clearly supported: When vision overstated the amount of rotation, pain occurred at 7% less rotation than under conditions of accurate visual feedback, and when vision understated rotation, pain occurred at 6% greater rotation than under conditions of accurate visual feedback. We concluded that visual-proprioceptive information modulated the threshold for movement-evoked pain, which suggests that stimuli that become associated with pain can themselves trigger pain.

Contingency Learning Deficits and Generalization in Chronic Unilateral Hand Pain Patients

UNLABELLED Contingency learning, in particular the formation of danger beliefs, underpins conditioned fear and avoidance behavior, yet equally important is the formation of safety beliefs. That is, when threat beliefs and accompanying fear/avoidance spread to technically safe cues, it might cause disability. Indeed, such over generalization has been advanced as a trans-diagnostic pathologic marker, but it has not been investigated in chronic pain. Using a novel hand pain scenario contingency learning task, we tested the hypotheses that chronic hand pain patients demonstrate less differential pain expectancy judgments because of poor safety learning and demonstrate broader generalization gradients than healthy controls. Participants viewed digitized 3-dimensional hands in different postures presented in random order (conditioned stimulus [CS]) and rated the likelihood that a fictive patient would feel pain when moving the hand into that posture. Subsequently, the outcome (pain/no pain) was presented on the screen. One hand posture was followed by pain (CS+), another was not (CS-). Generalization was tested using novel hand postures (generalization stimuli) that varied in how similar they were to the original conditioned stimuli. Patients, but not healthy controls, demonstrated a contingency learning deficit determined by impaired safety learning, but not by exaggerated pain expectancy toward the CS+. Patients showed flatter, asymmetric generalization gradients than the healthy controls did, with higher pain expectancy for novel postures that were more similar to the original CS-. The results clearly uphold our hypotheses and suggest that contingency learning deficits might be important in the development and maintenance of the chronic pain-related disability. PERSPECTIVE Chronic hand pain patients demonstrate 1) reduced differential contingency learning determined by a lack of safety belief formation, but not by exaggerated threat belief formation, and 2) flatter, asymmetric generalization gradients than the healthy controls.

A New Kind of Spatial Inattention Associated With Chronic Limb Pain

Pathological limb pain patients show decreased attention to some stimuli on the painful limb and increased attention to others, a paradox that has dogged the field for over a decade. We hypothesized that pathological pain involves a spatial inattention confined to bodily representations. Patients showed inattention to the painful side for visual processing of body parts but not letters, tactile processing but not auditory, and body‐part bisection tasks but not line bisection tasks. We propose the new term “somatospatial inattention” to describe bodily‐specific spatial inattention associated with pathological limb pain. Ann Neurol 2016;79:701–704

Can Pain or Hyperalgesia Be a Classically Conditioned Response in Humans? A Systematic Review and Meta-Analysis

BACKGROUND Clinical scenarios of repeated pain usually involve both nociceptive and non-nociceptive input. It is likely that associations between these stimuli are learned over time. Such learning may underlie subsequent amplification of pain, or evocation of pain in the absence of nociception. METHODS We undertook a systematic review and meta-analysis to evaluate the evidence that allodynia or hyperalgesia can be a classically conditioned response. A sensitive search of the literature covered Medline, Embase, CINAHL, AMED, PubMed, Scopus, PsycArticles, PsycINFO, Cochrane Library, and Web of Science. Additional studies were identified by contacting experts and searching published reviews. Two reviewers independently assessed studies for inclusion, evaluated risk of bias, and extracted data. Studies were included if they aimed to elicit or amplify pain using a classical conditioning procedure in healthy, adult humans. Studies were excluded if they did not distinguish between classical conditioning and explicit verbal suggestion as learning sources, or did not use experiential learning. RESULTS Thirteen studies, with varying risk of bias, were included. Ten studies evaluated classically conditioned hyperalgesia: nine found hyperalgesia; one did not. Pooled effects (n = 8 with full data) showed a significant pain increase after conditioning (mean difference of 7.40 [95%CI: 4.00-10.80] on a 0-100 pain scale). Three studies evaluated conditioned allodynia and found conflicting results. CONCLUSION The existing literature suggests that classical conditioning can amplify pain. No conclusions can be drawn about whether or not classical conditioning can elicit pain. Rigorous experimental conditioning studies with nociceptive unconditioned stimuli are needed to fill this gap in knowledge.

When touch predicts pain: predictive tactile cues modulate perceived intensity of painful stimulation independent of expectancy

Abstract Aims Non-nociceptive somatosensory input, such as tactile or proprioceptive information, alway precedes nociceptive input during a painful event. This relationship provides clear opportunities fo predictive associative learning, which may shape future painful experiences. In this differential classica conditioning study we tested whether pain-associated tactile cues (conditioned stimuli; CS) could altei the perceived intensity of painful stimulation, and whether this depends on duration of the CS—seeing that CS duration might allow or prevent conscious expectation. Methods Subjects underwent a classical differential conditioning task in which a tactile cue at locatior A (CS+) preceded painful electrical stimulation at location B (UShigh), whereas a tactile cue at location C (CS–) preceded non-painful electrical stimulation at location B (USlow). At test, we compared the pain evoked by a moderately painful stimulus (USmed) when preceded by either the CS+ or CS–. CS duration was manipulated between subjects. Participants were assigned to one of three groups: Long CS (4s, allowing conscious expectation), Short CS (110 ms) and CS-US indistinguishable (20 ms), preventing conscious expectation). We hypothesised that more pain would be evoked by the US when preceded by the CS+ relative to the CS-, and that the effect would be independent of CS duration. Results Fifty-four healthy participants (31 females, age = 26, SD = 9) were included in the analysis. The hypotheses were supported in that more intense pain was evoked by the USmed when paired with the tactile CS+, than when paired with the tactile CS-; mean difference 3 mm on a 150 mm VAS (C 0.4-4.8 mm). CS duration did not moderate the effect. The effect was greater in those participants where calibration was optimal, as indicated by a relatively more painful UShigh. Conclusions We conclude that pain-associated tactile cues can influence pain, and that this effect i: not dependent on stimulus duration. This suggests that explicit expectation is not a requirement for predictive cues to modulate pain. That the presence of the CS+ resulted in only a 5.3% higher intensity rating compared with the CS- may reflect a limitation of laboratory studies, where a limited number o trials, an artificial context and the use of experimental pain are likely to reveal only glimpses of what i: clinically possible. Implications Pain-associated visual and auditory cues have been shown to enhance pain in laboratory and clinical scenarios, supposedly by influencing expectation of impending harm. We show that pain-associated somatosensory cues can also modulate pain and that this can occur independently of expectation. This points to a larger potential role for associative learning in the development and treatment of pain than has previously been considered. We suggest that research into associative mechanisms underpinning pain, as distinct from those that link pain to pain-related fear and avoidance, is worthwhile.

Exploring changes in the brain associated with recovery from phantom limb pain – the potential importance of telescoping

In this issue, you will find a paper entitled ‘Mirror therapy for phantom limb pain: Brain changes and the role of body representation’ (Foell et al. 2014). Thirteen amputees with chronic phantom limb pain (PLP) participated in a 4-week mirror therapy programme. Functional brain imaging measures taken before and after the programme were related to change in PLP over the same period. Phantom limbs have long fascinated psychologists, neuroscientists and neurologists. That the phantom can be distorted speaks to the plasticity of the brain’s representation of the body and flags the potential opportunity for treatments that directly target these representations (see Moseley et al., 2012 for review). Mirror therapy is one such treatment. Foell et al. suggest that mirror therapy aims to re-establish normal cortical representations using visual input of an intact limb as a substitute for the now-missing proprioceptive feedback from the amputated limb. Systematic review suggests that mirror therapy probably reduces PLP, at least for some patients (Bowering et al., 2012). The study by Foell et al. raises two particularly intriguing results that have the potential to shift our thinking with regard to PLP and cortical representations. First, eight participants had a telescoping phantom and their PLP did not change over the treatment period. In contrast, five patients had a non-telescoping phantom and their PLP halved. Think of how remarkable this is – 16 years after amputation, just 15 min a day for a month. Is such a fabulous result attributable to the mirror therapy? There was no control condition nor group (which the authors acknowledge), and timeline was not jittered, so non-treatment factors – time, regression to the mean and ‘non-specific’ components – could all have contributed. This is important and we would contend that to conclude on the basis of this study that mirror therapy is effective is conjecture. Is the fabulous result attributable to having a nontelescoping phantom? It would seem highly unlikely that this alone would bring pain relief – if so, people with an intact phantom should not have PLP, which they clearly do. We think the two most likely explanations for the difference between groups are (1) that non-treatment factors introduced by researchers and clinicians not being blinded to phantom type and (2) that treatment based on mirror therapy is effective for amputees with an intact phantom, but not for amputees with a telescoping phantom. The latter explanation is clearly more seductive but the former should not, and cannot, be discounted on the basis of this study. Blinding the research/clinical team to the type of phantom, or at least assessing the expectations of the team and patients about the relationship between a telescoping phantom and response to mirror therapy, would greatly strengthen the case for the latter. That said, the remarkable contrast between the telescopers and the non-telescopers begs a second look, and we think the authors have every reason to now test this hypothesis in an a priori design. If such a study went on to support the current result, then it would imply that PLP patients with telescoping phantoms not be referred to mirror therapy-based treatment, which would in turn greatly elevate our expectations of a positive response. But why would mirror therapy be ineffective in the case of telescoping phantoms? The authors suggest that the mismatch between what the limb feels like, and how it looks during mirror therapy, is the likely reason and their data seem supportive of this idea and suggest that first enhancing the congruence between what one sees and what one feels, perhaps via virtual reality, might improve mirror therapy effects on PLP. The second intriguing result relates to the brain imaging data. Across the whole cohort, there was no change in cortical activation during lip or hand movement tasks between preand post-treatment. Yet the five patients with an intact, non-telescoping phantom showed normalization of primary sensory cortex activation during lip pursing, a normalization that was very strongly related to reduction in PLP (r = 0.75).

Neck Pain and Proprioception Revisited Using the Proprioception Incongruence Detection Test.

Background Proprioceptive imprecision is believed to contribute to persistent pain. Detecting imprecision in order to study or treat it remains challenging given the limitations of current tests. Objectives The aim of this study was to determine whether proprioceptive imprecision could be detected in people with neck pain by testing their ability to identify incongruence between true head motion and a false visual reference using the Proprioception Incongruence Detection (PID) Test. Design A cross-sectional study was conducted. Methods Twenty-four people with neck pain and 24 matched controls repeatedly rotated to specific markers within a virtual world and indicated if their true head rotation was more or less than the rotation suggested by the visual feedback. Visual feedback was manipulated at 6 corrections, ranging from 60% of true movement to 140% of true movement. A standard repositioning error (RPE) test as undertaken for comparison. Results Healthy controls were better able to detect incongruence between vision and true head rotation (X̅=75.6%, SD=8.5%) than people with neck pain were (X̅=69.6%, SD=12.7%). The RPE test scores were not different between groups. The PID Test score related to self-reported pain intensity but did not relate to RPE test score. Limitations Causality cannot be established from this cross-sectional study, and further work refining the PID Test is needed for it to offer clinical utility. Conclusions Proprioceptive precision for neck movement appears worse in people with neck pain than in those without neck pain, and the extent of the deficit appears to be related to usual pain severity. The PID Test appears to be a more sensitive test than the RPE test and is likely to be useful for assessment of proprioceptive function in research and clinical settings.

Contextual modulation of pain sensitivity utilising virtual environments

Background: Investigating psychological mechanisms that modulate pain, such as those that might be accessed by manipulation of context, is of great interest to researchers seeking to better understand and treat pain. The aim of this study was to better understand the interaction between pain sensitivity, and contexts with inherent emotional and social salience – by exploiting modern immersive virtual reality (VR) technology. Methods: A within-subjects, randomised, double-blinded, repeated measures (RM) design was used. In total, 25 healthy participants were exposed to neutral, pleasant, threatening, socially positive and socially negative contexts, using an Oculus Rift DK2. Pressure pain thresholds (PPTs) were recorded in each context, as well as prior to and following the procedure. We also investigated whether trait anxiety and pain catastrophisation interacted with the relationship between the different contexts and pain. Results: Pressure pain sensitivity was not modulated by context (p = 0.48). Anxiety and pain catastrophisation were not significantly associated with PPTs, nor did they interact with the relationship between context and PPTs. Conclusion: Contrary to our hypothesis, socially and emotionally salient contexts did not influence pain thresholds. In light of other research, we suggest that pain outcomes might only be tenable to manipulation by contextual cues if they specifically manipulate the meaning of the pain-eliciting stimulus, rather than manipulate psychological state generally – as per the current study. Future research might exploit immersive VR technology to better explore the link between noxious stimuli and contexts that directly alter its threat value.

Comparison of spatial summation properties at different body sites

Abstract Background and aims The nociceptive system appears to have evolved a range of protective characteristics that are of great interest in understanding both acute and chronic pain. Spatial summation is one important characteristic, whereby increasing area of a stimulus, or distance between multiple stimuli, results in more intense pain—not only greater area of pain. One of the mysteries of chronic pain is why spinal pain is so prevalent relative to pain at other sites. Since pathological tissue models have failed to fully explain spinal pain, we theorized that body region specific differences in sensory processing—such as a greater propensity for spatial summation—may help to explain its vulnerability. We aimed to examine this by comparing the properties of summation at different body parts: the dorsal forearm, neck, and back. Methods Spatial summation of pain was investigated using noxious intra-dermal electrical stimuli in healthy pain-free adults (14 males, 6 females), and the perceived pain intensity was rated on a 0-100 pain scale. Area-based stimulation was investigated by doubling the stimulation area with the addition of a second electrode placed adjacent to the first. Distance-based summation was investigated by randomly varying the separation distance between paired noxious electrical stimuli at separations of 0,10,15, and 20 cm. Results This study demonstrated that the properties of area- and distance-based summation are uniform across the neck, back, and forearm in healthy adults. Spatial summation of pain was also found to be greatest at 15- and 20-cm paired separations for all body regions tested, confirming that noxious information can be integrated over an extensive anatomical area. Conclusion Data from this investigation refutes the thesis that spatial summation of pain may be a contributing factor for the reported difference in chronicity rates between spinal and peripheral sites. It remains, however, a potentially important mechanism by which noxious inputs from multi-level pathology might integrate and contribute to pain. Implications While data from this project suggest that there are no regional differences in the properties of spatial summation of noxious stimuli, regional differences in other characteristics of the nociceptive system may yet provide insight into why some spinal pain is so highly prevalent; nociceptive distance-based summation may be highly relevant where two or more conditions co-exist in close proximity.