A proposed mechanism of chronic pain is dysregulation between the main inhibitory (GABA) and excitatory (glutamate) neurometabolites of the central nervous system. The level of these neurometabolites appears to differ in individual studies of people with pain compared to pain-free controls across different pain conditions. However, this has yet to be systematically investigated. To establish whether GABA, glutamate, glutamine and Glx levels differ across pain conditions when compared to pain-free controls. Five databases were searched. Studies were included if they investigated: 1) A pain condition compared to control. 2) Reported GABA, glutamate, glutamine or glutamate/glutamine level. 3) Used 1H-Magnetic Resonance Spectroscopy (Prospero Project ID CRD42018092170). Data extracted included neurometabolite level, pain diagnosis, and spectroscopy parameters. Meta-analyses were conducted to establish the difference in neurometabolite level between participants with pain and pain-free controls for different pain conditions. The MRS-Q was developed from existing clinical consensus to allow for the assessment of quality in the included studies. Thirty-five studies were included investigating combinations of migraine (n = 11), musculoskeletal pain (n = 8), chronic pain syndromes (n = 9) and miscellaneous pain (n = 10). Higher GABA levels were found in participants with migraine compared to controls (Hedge's G 0.499, 95%CI: 0.2 to 0.798). In contrast, GABA levels in musculoskeletal pain conditions (Hedge's G -0.189, 95%CI: 0.530 to 0.153) and chronic pain syndromes (Hedge's G 0.077, 95%CI: 1.612 to 1.459) did not differ from controls. Results for other brain neurometabolites revealed significantly higher levels for glutamate in participants with migraine and Glx in chronic pain syndromes compared to controls. These results support the theory that underlying neurometabolite levels may be unique in different pain conditions and therefore representative of biomarkers for specific pain conditions.

The aim of this guideline is to provide a series of evidence-based recommendations that allow those new to using MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats. The guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesized and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds. The final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel. These 23 expert-reviewed recommendations and accompanying extended documentation form a readily useable guideline to allow those new to using MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data.

Non-specific shoulder pain (NSSP) is often persistent and disabling leading to high socioeconomic costs. Cervical manipulation has demonstrated improvements in patients with NSSP, although risks associated with thrust techniques are documented. Thoracic manual therapy (TMT) may utilise similar neurophysiological effects with less risk. The current evidence for TMT in treating NSSP is limited to systematic reviews of manual therapy (MT) applied to the upper quadrant. These reviews included trials that used shoulder girdle manual therapy (SG-MT) in the TMT group. This limits the scope of their conclusions with regard to the exclusive effectiveness of TMT for NSSP. This review used a steering group for subject and methodological expertise and was reported in line with Preferred Reporting items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Key databases were searched (1990-2014) using relevant search terms and medical subject headings (MeSH); eligibility was evaluated independently by two reviewers based on pre-defined criteria. Study participants had NSSP including impingement syndrome and excluding cervical pain. Interventions included cervicothoracic junction and TMT with or without supplementary exercises. Studies that included MT applied to the shoulder girdle including the glenohumeral joint, acromioclavicular joint or sternoclavicular joint in the TMT group, without a control, were excluded. Included studies utilised outcome measures that monitored pain and disability scores. Randomized controlled trials (RCTs) and clinical studies were eligible. Using a standardised form, each reviewer independently extracted data. Risk of bias was assessed using GRADE and PEDro scale. Results were tabulated for semi-quantitative comparison. Over 912 articles were retrieved: three RCTs, one single-arm trial and three pre-post test studies were eligible. Studies varied from poor to high quality. Three RCTs demonstrated that TMT reduced pain and disability at 6, 26 and 52 weeks compared with usual care. Two pre-post test studies found between 76% and 100% of patients experienced significant pain reduction immediately post-TMT. An additional pre-post test study and a single-arm trial showed reductions in pain and disability scores 48 hours post-TMT. Thoracic manual therapy accelerated recovery and reduced pain and disability immediately and for up to 52 weeks compared with usual care for NSSP. Further, high-quality RCTs investigating the effect of TMT in isolation for the treatment of patients with NSSP are now required.

Background: People with chronic neck pain have impaired proprioception (i.e., sense of neck position). It is unclear whether this impairment involves disruptions to the proprioceptive representation in the brain, peripheral factors, or both. Implicit motor imagery tasks, namely left/right judgements of body parts, assess the integrity of the proprioceptive represention. Previous studies evaluating left/right neck judgements in people with neck pain are conflicting. We conducted a large online study to comprehensively address whether people with neck pain have altered implicit motor imagery performance.Methods: People with and without neck pain completed online left/rightneckjudgement tasks followed by a left/righthandjudgement task (control). Participants judged whether the person in the image had their head rotated to their left or right side (neck task) or whether the image was of a left hand or a right hand (hand task). Participants were grouped on neck pain status (no pain; <3 months—acute; ≥3 months—chronic) and pain location (none, left-sided, right-sided, bilateral). Outcomes included accuracy (primary) and response time (RT; secondary). Our hypotheses—that (i) chronic neck pain is associated with disrupted performance for neck images and (ii) the disruption is dependent on the side of usual pain, were tested with separate ANOVAs.Results: A total of 1,404 participants were recruited: 105 reported acute neck pain and 161 reported chronic neck pain. When grouped on neck pain status, people with chronic neck pain were less accurate than people without neck pain (p= 0.001) for left/right neck judgements, but those with acute neck pain did not differ from those without neck pain (p= 0.14) or with chronic neck pain (p= 0.28). Accuracy of left/right hand judgements did not differ between groups (p= 0.58). RTs did not differ between groups for any comparison. When grouped on neck pain location, people were faster and more accurate at identifying right-turning neck images than left-turning neck images, regardless of history or location of pain (p< 0.001 for both); people with no pain were more accurate and faster than people with bilateral neck pain (p= 0.001,p= 0.015) and were faster than those with left-sided neck pain (p= 0.021); people with right-sided neck pain were more accurate than people with bilateral neck pain (p= 0.018). Lastly, there was a significant interaction between neck image and side of neck pain: people with right-sided neck pain were more accurate at identifying right-sided neck turning images than people with left-sided neck pain (p= 0.008), but no different for left-sided neck turning images (p= 0.62).Conclusions: There is evidence of impaired implicit motor imagery performance in people with chronic neck pain, which may suggest disruptions to proprioceptive representation of the neck. These disruptions seem specific to the neck (performance on hand images intact) but non-specific to the exact location of neck pain.

Traumatic upper limb peripheral nerve injuries significantly impact individuals’ function and ability to return to work. Patients with peripheral nerve injury experience ongoing psychological impairments for which they are not routinely treated. The aim of this review was to investigate the psychological consequences of traumatic upper limb peripheral nerve injury. A systematic review of MEDLINE, Embase, PsycINFO, CINAHL, AMED, BNI, the Cochrane libraries and grey literature up to October 2015 was undertaken. Two reviewers independently assessed methodological quality in accordance with Cochrane Collaboration recommendations. Eligibility criteria comprised: adults or adolescents with traumatic upper limb peripheral nerve injury using any measurement of psychological well-being. Six studies (n = 245) met the inclusion criteria. Methodological quality varied widely. Evidence of post-traumatic stress disorder at one month, which decreased over time, was reported in three studies. Two studies found a statistically significant correlation between the early presence of post-traumatic stress disorder and reduction in function at 12 or more months. Limited information was available on anxiety, depression and mental quality of life. Combined nerve injuries (in two studies) had significantly higher levels of post-traumatic stress disorder, at one month, compared to those with an isolated nerve injury. There is some evidence of early post-traumatic stress disorder following traumatic upper limb peripheral nerve injury, which may have an impact on functional outcome. However, high-quality studies using prospective cohorts are required to further evaluate the psychological aspects associated with this traumatic injury.