G. L. Moseley

The rubber hand illusion increases histamine reactivity in the real arm

Summary Most people are convinced that their body parts are in fact their own, but in some clinical conditions, this sense of ownership can be lost [1]. Perceptual illusions, most famously the rubber hand illusion (RHI) [2], demonstrate that a sense of ownership over a body part (or an entire body [3]) that is not in fact ours can be easily induced in healthy volunteers. But does illusory ownership over an artificial body part have consequences for the real body part, the one that has been ‘replaced? Recent data show the RHI induces a small but robust drop in skin temperature of the real hand. That is, blood flow to the ‘disowned hand seems to be selectively reduced [1]. Such a finding is particularly relevant to the immune system because a primary role of the immune system is to ‘discriminate self from non-self [4]. We predicted that the innate immune system may be upregulated in a manner consistent with rejection of the replaced hand. Consistent with this prediction, we report here that the RHI increases histamine reactivity, which is a key final pathway of the innate immune response and has been implicated in autoimmune disorders, including multiple sclerosis [5]. Our finding has direct implications for autoimmune disorders and a range of neurological and psychiatric conditions characterised by a disrupted sense of ownership over ones body (see [1] for a list of conditions), and has broader implications that extend well beyond previous assertions about the mind-body link.

How does pain lead to disability? A systematic review and meta-analysis of mediation studies in people with back and neck pain

Abstract Disability is an important outcome from a clinical and public health perspective. However, it is unclear how disability develops in people with low back pain or neck pain. More specifically, the mechanisms by which pain leads to disability are not well understood. Mediation analysis is a way of investigating these mechanisms by examining the extent to which an intermediate variable explains the effect of an exposure on an outcome. This systematic review and meta-analysis aimed to identify and examine the extent to which putative mediators explain the effect of pain on disability in people with low back pain or neck pain. Five electronic databases were searched. We found 12 studies (N = 2961) that examined how pain leads to disability with mediation analysis. Standardized regression coefficients (&bgr;) of the indirect and total paths were pooled. We found evidence to show that self-efficacy (&bgr; = 0.23, 95% confidence interval [CI] = 0.10 to 0.34), psychological distress (&bgr; = 0.10, 95% CI = 0.01 to 0.18), and fear (&bgr; = 0.08, 95% CI = 0.01 to 0.14) mediated the relationship between pain and disability, but catastrophizing did not (&bgr; = 0.07, 95% CI = −0.06 to 0.19). The methodological quality of these studies was low, and we highlight potential areas for development. Nonetheless, the results suggest that there are significant mediating effects of self-efficacy, psychological distress, and fear, which underpins the direct targeting of these constructs in treatment.

Mislocalization of sensory information in people with chronic low back pain: A preliminary investigation

Objectives:The purpose of this study was to establish if people with chronic low back pain (CLBP) demonstrate impairments in the ability to localize sensory information delivered to the back more than pain-free controls and determine whether any sensory abnormalities are related to pain-related variables. Methods:Vision was occluded and participants were stimulated using light touch or pinprick over a number of body areas in random order. To assess for mislocalizations participants were asked to nominate the location of each stimulus in reference to a marked body chart. To assess referred sensations participants who were asked whether they experienced any sensations elsewhere during stimulation. If referred sensations were reported, testing was repeated with visualization of the stimulated area. Results:Although a small number of CLBP patients demonstrated referral of sensations, this was not statistically different from what was observed in a pain-free control group (P=0.381). In contrast, mislocalizations were very common in the patient sample and statistically more common than we found in controls (P=0.034). No statistically significant associations were detected between sensory function and the measured pain-related variables (all P>0.05). Discussion:These data add to a growing body of evidence suggesting that disturbed self-perception is a feature of CLBP. It is plausible that altered self-perception is maladaptive and contributes to the maintenance of the problem and may represent a target of treatment for CLBP.

Does changing pain-related knowledge reduce pain and improve function through changes in catastrophizing?

Abstract Evidence from randomized controlled studies shows that reconceptualizing pain improves patients knowledge of pain biology, reduces catastrophizing thoughts, and improves pain and function. However, causal relationships between these variables remain untested. It is hypothesized that reductions in catastrophizing could mediate the relationship between improvements in pain knowledge and improvements in pain and function. To test this causal mechanism, we conducted longitudinal mediation analyses on a cohort of 799 patients who were exposed to a pain education intervention. Patients provided responses to the neurophysiology of pain questionnaire, catastrophic thoughts about pain scale, visual analogue pain scale, and the patient specific functional scale, at baseline, 1-month, 6-month, and 12-month follow-up. With adjustment for potential confounding variables, an improvement in pain biology knowledge was significantly associated with a reduction in pain intensity (total effect = −2.20, 95% confidence interval [CI] = −2.96 to −1.44). However, this effect was not mediated by a reduction in catastrophizing (indirect effect = −0.16, 95% CI = −0.36 to 0.02). This might be due to a weak, nonsignificant relationship between changes in catastrophizing and pain intensity (path b = 0.19, 95% CI = −0.03 to 0.41). Similar trends were found in models with function as the outcome. Our findings indicate that change in catastrophizing did not mediate the effect of pain knowledge acquisition on change in pain or function. The strength of this conclusion is moderated, however, if patient-clinician relational factors are conceptualized as a consequence of catastrophizing, rather than a cause.

Emotional distress drives health services overuse in patients with acute low back pain: a longitudinal observational study

PurposeTo determine whether emotional distress reported at the initial consultation affects subsequent healthcare use either directly or indirectly via moderating the influence of symptoms.MethodsLongitudinal observational study of 2891 participants consulting primary care for low back pain. Negative binomial regression models were constructed to estimate independent effects of emotional distress on healthcare use.xa0Potential confounders were identified using directed acyclic graphs.ResultsAfter the initial consultation, participants had a mean (SD) of one (1.2) visit for back pain over 3xa0months, and nine (14) visits for back pain over 12xa0months. Higher reports of anxiety during the initial consultation led to increased short-term healthcare use (IRR 1.06, 95xa0% CI 1.01–1.11) and higher reports of depression led to increased long-term healthcare use (IRR 1.04, 95xa0% CI 1.02–1.07). The effect sizes suggest that a patient with a high anxiety score (8/10) would consult 50xa0% more frequently over 3xa0months, and a person with a high depression score (8/10) would consult 30xa0% more frequently over 12xa0months, compared to a patient with equivalent pain and disability and no reported anxiety or depression.ConclusionsEmotional distress in the acute stage of low back pain increased subsequent consultation rates. Interventions that target emotional distress during the initial consultation are likely to reduce costly and potentially inappropriate future healthcare use for patients with non-specific low back pain.

Finding the balance in complex regional pain syndrome: Expertise, optimism, and evidence.

Complex regional pain syndrome (CRPS), perhaps more than any other chronic pain disorder, is perplexing. It is highly disabling, particularly once it has “set in,” and it has a tendency to polarize the community—some view it as a quasidiagnosis to obscure malingering or conceal substandard clinical skills,1 and others as a multiple system overprotective response.2 What is agreed is that its pathophysiology is not completely understood and that it is difficult to treat. In light of this rather murky backdrop, we welcome the new perspectives article in this issue of Neurology® by Birklein et al.3 They describe their own clinical approach to the problem and their impressions of what works, what does not, and where the field might be heading. The lead author is the most prolific and arguably the most important researcher in this field, and the article clearly draws on a wealth of expertise and clinical experience probably unmatched globally. The article reminds us of the remaining substantial challenges that we face: for example, the need for prospective studies, higher quality clinical trials and audits, and a putative model that accounts for the transition from acute CRPS to chronic CRPS, which is arguably characterized by distinct pathophysiology. Anyone who treats a good number of CRPS patients will recognize the clinical patterns to which the authors allude and be comforted by the realization that even this group, at the top of the field, share the same substantial treatment challenges.

Causal mechanisms in the clinical course and treatment of back pain.

In recent years, there has been increasing interest in studying causal mechanisms in the development and treatment of back pain. The aim of this article is to provide an overview of our current understanding of causal mechanisms in the field. In the first section, we introduce key concepts and terminology. In the second section, we provide a brief synopsis of systematic reviews of mechanism studies relevant to the clinical course and treatment of back pain. In the third section, we reflect on the findings of our review to explain how understanding causal mechanisms can inform clinical practice and the implementation of best practice. In the final sections, we introduce contemporary methodological advances, highlight the key assumptions of these methods, and discuss future directions to advance the quality of mechanism-related studies in the back pain field.

The reliability of eyetracking to assess attentional bias to threatening words in healthy individuals

Eyetracking is commonly used to investigate attentional bias. Although some studies have investigated the internal consistency of eyetracking, data are scarce on the test–retest reliability and agreement of eyetracking to investigate attentional bias. This study reports the test–retest reliability, measurement error, and internal consistency of 12 commonly used outcome measures thought to reflect the different components of attentional bias: overall attention, early attention, and late attention. Healthy participants completed a preferential-looking eyetracking task that involved the presentation of threatening (sensory words, general threat words, and affective words) and nonthreatening words. We used intraclass correlation coefficients (ICCs) to measure test–retest reliability (ICC > .70 indicates adequate reliability). The ICCs(2, 1) ranged from –.31 to .71. Reliability varied according to the outcome measure and threat word category. Sensory words had a lower mean ICC (.08) than either affective words (.32) or general threat words (.29). A longer exposure time was associated with higher test–retest reliability. All of the outcome measures, except second-run dwell time, demonstrated low measurement error (<6%). Most of the outcome measures reported high internal consistency (α > .93). Recommendations are discussed for improving the reliability of eyetracking tasks in future research.

An embedded randomised controlled trial of a Teaser Campaign to optimise recruitment in primary care

Background: Marketing communication and brand identity is a fundamental principle of advertising and end-user engagement. Health researchers have begun to apply this principle to trial recruitment in primary care. The aim of this study was to evaluate whether a Teaser Campaign using a series of postcards in advance of a conventional mail-out increases the number of primary care clinics that engage with a clinical trial. Methods: Embedded randomised recruitment trial across primary care clinics (general practitioners and physiotherapists) in the Sydney metropolitan area. Clinics in the Teaser Campaign group received a series of branded promotional postcards in advance of a standard letter inviting them to participate in a clinical trial. Clinics in the Standard Mail group did not receive the postcards. Results: From a total of 744 clinics that were sent an invitation letter, 46 clinics in the Teaser Campaign group and 40 clinics in the Standard Mail group responded (11.6% total response rate). There was no between-group difference in the odds of responding to the invitation letter (odds ratiou2009=u20091.18, 95% confidence intervalu2009=u20090.75–1.85, pu2009=u20090.49). For physiotherapy clinics and general practice clinics, the odds ratios were 1.43 (confidence intervalu2009=u20090.82–2.48, pu2009=u20090.21) and 0.77 (confidence intervalu2009=u20090.34–1.75, pu2009=u20090.54), respectively. Conclusion: A Teaser Campaign using a series of branded promotional postcards did not improve clinic engagement for a randomised controlled trial in primary care.

Reproducible and replicable pain research: a critical review.

Publication Information Lee, Hopin, Lamb, Sarah E., Bagg, Matthew K., Toomey, Elaine, Cashin, Aidan G., & Moseley, G. Lorimer. (2018). Reproducible and replicable pain research: a critical review. PAIN, 159(9), 1683-1689. doi: 10.1097/j.pain.0000000000001254 Publisher Lippincott, Williams & Wilkins for International Association for the Study of Pain Link to publishers version https://journals.lww.com/pain/fulltext/2018/09000/Reproducibl e_and_replicable_pain_research___a.5.aspx