We conducted a systematic review and meta-analysis of prospective cohort studies of subjects with acute whiplash injuries. The aim was to describe the course of recovery, pain and disability symptoms and also to assess the influence of different prognostic factors on outcome. Studies were selected for inclusion if they enrolled subjects with neck pain within six weeks of a car accident and measured pain and/or disability outcomes. Studies were located via a sensitive search of electronic databases; Medline, Embase, CINAHL, Cochrane database, ACP Journal club, DARE and Psychinfo and through hand-searches of relevant previous reviews. Methodological quality of all studies was assessed using a six item checklist. Sixty-seven articles, describing 38 separate cohorts were included. Recovery rates were extremely variable across studies but homogeneity was improved when only data from studies of more robust methodological quality were considered. These data suggest that recovery occurs for a substantial proportion of subjects in the initial 3 months after the accident but after this time recovery rates level off. Pain and disability symptoms also reduce rapidly in the initial months after the accident but show little improvement after 3 months have elapsed. Data regarding the prognostic factors associated with poor recovery were difficult to interpret due to heterogeneity of the techniques used to assess such associations and the way in which they are reported. There was also wide variation in the measurement of outcome and the use of validated measures would improve interpretability and comparability of future studies.

Sensitization of the nervous system can present as pain hypersensitivity that may contribute to clinical pain. In spinal pain, however, the relationship between sensory hypersensitivity and clinical pain remains unclear. This systematic review examined the relationship between pain sensitivity measured via quantitative sensory testing (QST) and self-reported pain or pain-related disability in people with spinal pain. Electronic databases and reference lists were searched. Correlation coefficients for the relationship between QST and pain intensity or disability were pooled using random effects models. Subgroup analyses and mixed effects meta-regression were used to assess whether the strength of the relationship was moderated by variables related to the QST method or pain condition. One hundred and forty-five effect sizes from 40 studies were included in the meta-analysis. Pooled estimates for the correlation between pain threshold and pain intensity were -0.15 (95% confidence interval [CI]: -0.18 to -0.11) and for disability -0.16 (95% CI: -0.22 to -0.10). Subgroup analyses and meta-regression did not provide evidence that these relationships were moderated by the QST testing site (primary pain/remote), pain condition (back/neck pain), pain type (acute/chronic), or type of pain induction stimulus (eg, mechanical/thermal). Fair correlations were found for the relationship between pain intensity and thermal temporal summation (0.26, 95% CI: 0.09 to 0.42) or pain tolerance (-0.30, 95% CI: -0.45 to -0.13), but only a few studies were available. Our study indicates either that pain threshold is a poor marker of central sensitization or that sensitization does not play a major role in patients' reporting of pain and disability. Future research prospects are discussed.

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.

Background: There is uncertainty about the optimal approach to screen for clinically important cervical spine (C-spine) injury following blunt trauma. We conducted a systematic review to investigate the diagnostic accuracy of the Canadian C-spine rule and the National Emergency X-Radiography Utilization Study (NEXUS) criteria, 2 rules that are available to assist emergency physicians to assess the need for cervical spine imaging. Methods: We identified studies by an electronic search of CINAHL, Embase and MEDLINE. We included articles that reported on a cohort of patients who experienced blunt trauma and for whom clinically important cervical spine injury detectable by diagnostic imaging was the differential diagnosis; evaluated the diagnostic accuracy of the Canadian C-spine rule or NEXUS or both; and used an adequate reference standard. We assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies criteria. We used the extracted data to calculate sensitivity, specificity, likelihood ratios and post-test probabilities. Results: We included 15 studies of modest methodologic quality. For the Canadian C-spine rule, sensitivity ranged from 0.90 to 1.00 and specificity ranged from 0.01 to 0.77. For NEXUS, sensitivity ranged from 0.83 to 1.00 and specificity ranged from 0.02 to 0.46. One study directly compared the accuracy of these 2 rules using the same cohort and found that the Canadian C-spine rule had better accuracy. For both rules, a negative test was more informative for reducing the probability of a clinically important cervical spine injury. Interpretation: Based on studies with modest methodologic quality and only one direct comparison, we found that the Canadian C-spine rule appears to have better diagnostic accuracy than the NEXUS criteria. Future studies need to follow rigorous methodologic procedures to ensure that the findings are as free of bias as possible.