Human Studies

Although complex regional pain syndrome (CRPS) of the knee is comparable to CRPS of the ankle/foot at time of diagnosis, no reports are available concerning the course of knee CRPS. Therefore, this study investigated the clinical course in terms of the symptoms and signs, health-related quality of life (HR-QoL), and work status of patients diagnosed with CRPS of the knee.

Recent neuroimaging studies implicate the medial temporal lobe (MTL) in nociception and pain modulation. Here, we aim to identify which subregions of the MTL are involved in human pain and to test its connectivity in a cohort of chronic low back pain patients (CBP). We conducted two coordinate-based meta-analyses to determine which regions within the MTL showed consistent spatial patterns of functional activation (1) in response to experimental pain in healthy participants, and (2) in chronic pain compared to healthy participants. We followed PRISMA guidelines and performed activation likelihood estimate (ALE) meta-analyses. The first meta-analysis revealed consistent activation in the right anterior hippocampus (right antHC), parahippocampal gyrus and amygdala. The second meta-analysis revealed consistently less activation in patients' right antHC, compared to healthy participants. We then conducted a seed-to-voxel resting state functional connectivity of the right antHC seed with the rest of the brain in 77 CBP and 79 age-matched healthy participants. We found that CBP had significantly weaker antHC functional connectivity to the medial prefrontal cortex (mPFC) compared to healthy participants. Taken together, these data indicate that the antHC has abnormally lower activity in chronic pain, and reduced connectivity to the mPFC in CBP. Future studies should investigate the specific role of the antHC in the development and management of chronic pain.

Despite optimal medical management (OMM), low back pain (LBP) can be disabling, particularly after spinal surgery. Spinal cord stimulation (SCS) is effective in reducing neuropathic leg pain; however, evidence is limited for LBP.This prospective, open-label, parallel-group trial randomized (1:1) failed back surgery syndrome (FBSS) patients with predominant LBP to SCS plus OMM (SCS group) or OMM alone (OMM group) in 28 sites in Europe and the Americas. If trial stimulation was successful, a SCS system was implanted. Outcomes were assessed at baseline (pre-randomization) and 1, 3, 6, and 12 months post-randomization. Patients could change treatment groups at 6 months. The primary outcome was the proportion of patients with ≥50% reduction in LBP (responder) at 6 months. Secondary outcomes included change in pain intensity, functional disability and health-related quality of life (HRQoL). Results are posted at ClinicalTrials.gov registration number NCT01697358.In the intent-to-treat analysis, there were more responders in the SCS group than the OMM group (13.6%,15/110 versus 4.6%, 5/108, difference 9% with 95% CI 0.6-17.5%, P=0.036) at 6 months. The SCS group improved in all secondary outcomes compared to the OMM group. The OMM group only improved in HRQoL. In the SCS group, 17.6% (18/102) experienced SCS-related AEs through 6 months, with 11.8% (12/102) requiring surgical re-intervention.Adding multicolumn SCS to OMM improved pain relief, HRQoL and function in a traditionally difficult to treat population of FBSS patients with predominant LBP. Improvements were sustained at 12 months.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.

Accumulating evidence has shown that complicated brain systems are involved in the development and maintenance of chronic low back pain (cLBP), but the association between brain functional changes and clinical outcomes remains unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to identify abnormal functional connectivity (FC) between the default mode, sensorimotor, salience, and central executive brain networks in cLBP and tested whether abnormal FCs are related to pain and comorbid symptoms. Fifty cLBP patients and 44 matched healthy controls (HCs) underwent an fMRI scan, from which brain networks were identified by independent component analysis. Multivariate pattern analysis, graph theory approaches, and correlation analyses were applied to find abnormal FCs that were associated with clinical symptoms. Findings were validated on a second cohort of 30 cLBP patients and 30 matched HCs. Results showed that the medial prefrontal cortex/rostral anterior cingulate cortex had abnormal FCs with brain regions within the default mode network and with other brain networks in cLBP patients. These altered FCs were also correlated with pain duration, pain severity, and pain interference. Finally, we found that resting-state FC could discriminate cLBP patients from HCs with 91% accuracy in the first cohort and 78% accuracy in the validation cohort. Our findings suggest that the medial prefrontal cortex/rostral anterior cingulate cortex may be an important hub for linking the default mode network with the other 3 networks in cLBP patients. Elucidating the altered FCs and their association with clinical outcomes will enhance our understanding of the pathophysiology of cLBP and may facilitate the development of pain management approaches.

Chronic neuropathic pain is a common challenging condition following amputation. Recent research demonstrated the feasibility of percutaneously implanting fine-wire coiled peripheral nerve stimulation (PNS) leads in proximity to the sciatic and femoral nerves for postamputation pain. A multicenter, double-blinded, randomized, placebo-controlled study collected data on the safety and effectiveness of percutaneous PNS for chronic neuropathic pain following amputation.

The neuropathophysiology of a debilitating chronic urologic pain condition, bladder pain syndrome (BPS), remains unknown. Our recent data suggests withdrawal of cardiovagal modulation in subjects with BPS, in contrast to sympathetic nervous system dysfunction in another chronic pelvic pain syndrome, myofascial pelvic pain (MPP). We evaluated whether comorbid disorders differentially associated with BPS vs MPP shed additional light on these autonomic differences.