Psychological consequences of Traumatic Upper Limb Peripheral Nerve Injury: A Systematic Review

Introduction 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. Methods 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. Results 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. Conclusion 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. </jats:sec

Brain Neurochemicals in Migraine and Pain

Migraine is the leading cause of neurological disability worldwide, with many treatments shown to be ineffective. Enhancing our understanding of mechanism of migraine may lead to the development of effective, migraine-specific treatments. Elevated Gamma-amino butyric acid (GABA) levels have been observed in people with migraine but not other pain conditions, suggesting GABA levels may indicate a mechanism responsible for migraine. Advances in magnetic resonance imaging (MRS), such as MEGA-PRESS, enable direct measurement of GABA in the human brain, although there is no agreed best practice for data acquisition. The thesis aims were to: 1) advance understanding of the role of GABA in migraine (and pain conditions) 2) improve the standardisation of methods for quality assessment, and accurate measurement and reporting of GABA in studies using MEGA-PRESS. Initially, GABA+ levels appeared to be unique to migraine when compared to other pain conditions in a meta-analysis (Chapter 2). However, a direct comparison of GABA+ levels in people with migraine, whiplash-headache and back pain compared to controls found GABA+ levels were elevated across all pain groups (Chapter 3). Finally, an increase in GABA+ levels over time were shown to be associated with decreased clinical measures of migraine (Chapter 3). Together these findings suggest GABA+ levels are a general pain-related measure in migraine and pain. To improve standardisation two new tools were developed. The MRS-Q a 12-point quality assessment tool for spectroscopy studies (Chapter 2) and The Comprehensive Guide to MEGA-PRESS (Chapter 5), an evidence-based guideline for best practice in GABA measurement. Together, the findings advance what is known about GABA in migraine and pain, and serves to shape future research into GABA through providing methods to standardise quality assessment, reporting and measurement of GABA using MEGA-PRESS

MRS-Q

This is the V1 template of MRS-

Thoracic manual therapy in the management of non-specific shoulder pain:A systematic review

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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

Brain GABA and glutamate levels across pain conditions:A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool

Background: 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. Aims: To establish whether GABA, glutamate, glutamine and Glx levels differ across pain conditions when compared to pain-free controls. Methods: 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. Results: 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. Conclusion: 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.</p

Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time

BACKGROUND: An imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules (“GABA+”) using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time. METHODS: We observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time. RESULTS: The results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = − 0.51, p = 0.03), intensity (r = − 0.51, p = 0.03) and disability (r = − 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8). CONCLUSION: The correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10194-021-01352-1

Increased GABA+ in People With Migraine, Headache, and Pain Conditions- A Potential Marker of Pain

Treatment outcomes for migraine and other chronic headache and pain conditions typically demonstrate modest results. A greater understanding of underlying pain mechanisms may better inform treatments and improve outcomes. Increased GABA+ has been identified in recent studies of migraine, however, it is unclear if this is present in other headache, and pain conditions. We primarily investigated GABA+ levels in the posterior cingulate gyrus (PCG) of people with migraine, whiplash-headache and low back pain compared to age- and sex-matched controls, GABA+ levels in the anterior cingulate cortex (ACC) and thalamus formed secondary aims. Using a cross-sectional design, we studied people with migraine, whiplash-headache or low back pain (n = 56) and compared them with a pool of age- and sex-matched controls (n = 22). We used spectral-edited magnetic resonance spectroscopy at 3T (MEGA-PRESS) to determine levels of GABA+ in the PCG, ACC and thalamus. PCG GABA+ levels were significantly higher in people with migraine and low back pain compared with controls (eg, migraine 4.89 IU ± 0.62 vs controls 4.62 IU ± 0.38; P = .02). Higher GABA+ levels in the PCG were not unique to migraine and could reflect a mechanism of chronic pain in general. A better understanding of pain at a neurochemical level informs the development of treatments that target aberrant brain neurochemistry to improve patient outcomes. PERSPECTIVE: This study provides insights into the underlying mechanisms of chronic pain. Higher levels of GABA+ in the PCG may reflect an underlying mechanism of chronic headache and pain conditions. This knowledge may help improve patient outcomes through developing treatments that specifically address this aberrant brain neurochemistry

Minimum Reporting Standards for in vivo Magnetic Resonance Spectroscopy (MRSinMRS): Experts' consensus recommendations

The translation of MRS to clinical practice has been impeded by the lack of technical standardization. There are multiple methods of acquisition, post-processing, and analysis whose details greatly impact the interpretation of the results. These details are often not fully reported, making it difficult to assess MRS studies on a standardized basis. This hampers the reviewing of manuscripts, limits the reproducibility of study results, and complicates meta-analysis of the literature. In this paper a consensus group of MRS experts provides minimum guidelines for the reporting of MRS methods and results, including the standardized description of MRS hardware, data acquisition, analysis, and quality assessment. This consensus statement describes each of these requirements in detail and includes a checklist to assist authors and journal reviewers and to provide a practical way for journal editors to ensure that MRS studies are reported in full