A decrease in glutamate in the medial prefrontal cortex (mPFC) has been extensively found in animal models of chronic pain. Given that the mPFC is implicated in emotional appraisal, cognition and extinction of fear, could a potential decrease in glutamate be associated with increased pessimistic thinking, fear and worry symptoms commonly found in people with chronic pain? To clarify this question, 19 chronic pain subjects and 19 age- and gender-matched control subjects without pain underwent magnetic resonance spectroscopy. Both groups also completed the Temperament and Character, the Beck Depression and the State Anxiety Inventories to measure levels of harm avoidance, depression, and anxiety, respectively. People with chronic pain had significantly higher scores in harm avoidance, depression and anxiety compared to control subjects without pain. High levels of harm avoidance are characterized by excessive worry, pessimism, fear, doubt and fatigue. Individuals with chronic pain showed a significant decrease in mPFC glutamate levels compared to control subjects without pain. In people with chronic pain mPFC glutamate levels were significantly negatively correlated with harm avoidance scores. This means that the lower the concentration of glutamate in the mPFC, the greater the total scores of harm avoidance. High scores are associated with fearfulness, pessimism, and fatigue-proneness. We suggest that chronic pain, particularly the stress-induced release of glucocorticoids, induces changes in glutamate transmission in the mPFC, thereby influencing cognitive, and emotional processing. Thus, in people with chronic pain, regulation of fear, worry, negative thinking and fatigue is impaired.

Fine motor control is achieved through the co-ordinated activation of groups of muscles, or "muscle synergies". Muscle synergies change after stroke as a consequence of the motor deficit. We investigated the pattern and longitudinal changes in upper-limb muscle synergies during therapy in a largely unconstrained movement in patients with a broad spectrum of post-stroke residual voluntary motor capacity. Electromyography (EMG) was recorded using wireless telemetry from 6 muscles acting on the more-affected upper body in 24 stroke patients at early- and late-therapy during formal Wii-based Movement Therapy sessions, and in a subset of 13 patients at 6-month follow-up. Patients were classified with low, moderate or high motor-function. The Wii-baseball swing was analysed using a non-negative matrix factorisation (NMF) algorithm to extract muscle synergies from EMG recordings based on the temporal activation of each synergy and the contribution of each muscle to a synergy. Motor-function was clinically assessed immediately pre- and post-therapy and at 6-month follow-up using the Wolf Motor Function Test, upper-limb motor Fugl-Meyer Assessment and Motor Activity Log Quality of Movement scale. Clinical assessments and game performance demonstrated improved motor-function for all patients at post-therapy (p0.05). NMF analysis revealed fewer muscle synergies (mean±SE) for patients with low motor-function (3.38±0.2) than those with high motor-function (4.00±0.3) at early-therapy (p=0.036) with an association trend between the number of synergies and the level of motor-function. By late-therapy there was no significant change between groups, although there was a pattern of increase for those with low motor-function over time. The variability accounted for (VAF) demonstrated differences with motor-function level but not time (p<0.05). Cluster analysis of the pooled synergies highlighted the therapy-induced change in muscle activation. Muscle synergies could be identified for all patients during therapy activities. These results show less complexity and more co-activation in the muscle activation for patients with low motor-function as a higher number of muscle synergies reflects greater movement complexity and task-related phasic muscle activation. The increased number of synergies and changes within synergies by late-therapy suggests improved motor control and movement quality with more distinct phases of movement.

Objectives: To investigate the effect of emotion regulation skills‐focused (ERSF) interventions to reduce pain intensity and improve psychological outcomes for people with chronic pain and to narratively report on safety and intervention compliance.Methods: Six databases and four registries were searched for randomized controlled trials (RCTs) up to 29 April 2022. Risk of bias was evaluated using the Cochrane RoB 2.0 tool, and certainty of evidence was assessed according to the Grading, Assessment, Development and Evaluation (GRADE). Meta‐analyses for eight studies (902 participants) assessed pain intensity (primary outcome), emotion regulation, affect, symptoms of depression and anxiety, and pain interference (secondary outcomes), at two time points when available, post‐intervention (closest to intervention end) and follow‐up (the first measurement after the post‐intervention assessment).Results: Compared to TAU, pain intensity improved post‐intervention (weighted mean difference [WMD] = −10.86; 95% confidence interval [CI] [−17.55, −2.56]) and at follow‐up (WMD = −11.38; 95% CI [−13.55, −9.21]). Emotion regulation improved post‐intervention (standard mean difference [SMD] = 0.57; 95% CI [0.14, 1.01]), and depressive symptoms improved at follow‐up (SMD = −0.45; 95% CI [−0.66, −0.24]). Compared to active comparators, anxiety symptoms improved favouring the comparator post‐intervention (SMD = 0.10; 95% CI [0.03, 0.18]), and compared to CBT, pain interference improved post‐intervention (SMD = −0.37; 95% CI [−0.69, −0.04]). Certainty of evidence ranged from very low to moderate.Significance: The findings provide evidence that ERSF interventions reduce pain intensity for people with chronic pain compared to usual treatment. These interventions are at least as beneficial to reduce pain intensity as the current gold standard psychological intervention, CBT. However, the limited number of studies and certainty of evidence mean further high‐quality RCTs are warranted. Additionally, further research is needed to identify whether ERSF interventions may be more beneficial for specific chronic pain conditions.

Background: Depressive symptoms are often comorbid with chronic pain. These conditions share aberrant emotion processing and regulation, as well as having common brain networks. However, the relationship between depressive symptoms and chronic pain and the effects on emotional brain function are unclear. Aims: The present study aimed to disentangle the effects of chronic pain and depressive symptoms on functional connectivity between regions implicated in both these conditions. Method: Twenty-six individuals with chronic pain (referred to as the pain group) and 32 healthy controls underwent resting-state functional magnetic resonance imaging and completed the Beck Depression Inventory. Main effects of group, depressive symptoms (total severity score) and their interaction on the functional connectivity of three seed regions (the left and right amygdalae and the medial prefrontal cortex; mPFC) with the rest of the brain were evaluated. In cases of significant interaction, moderation analyses were conducted. Results: The group × depressive symptoms interaction was significantly associated with changes in connectivity between the right amygdala and the mPFC (family-wise error-corrected P-threshold (pFWEc = 0.008). In the moderation analysis, the pain group showed weaker connectivity between these regions at lower levels of depressive symptoms (P = 0.020), and stronger connectivity at higher levels of depressive symptoms (P = 0.003), compared with the healthy controls. In addition, the strength of connectivity decreased in the healthy controls (P = 0.005) and increased in the pain group (P = 0.014) as the severity of depressive symptoms increased. Conclusions: Depressive symptoms moderate the impact of chronic pain on emotional brain function, with potential implications for the choice of treatment for chronic pain.