Abnormal Enhanced Gamma Synchronization in the Default Mode Network Associated With Chronic Pain

Chronic pain is a common and severely disabling disease whose treatment is often unsatisfactory. Insights into the brain mechanisms of chronic pain promise to advance the understanding of the underlying pathophysiology and might help to develop disease markers and novel treatments. Here, we systematically exploited the potential of electroencephalography to determine abnormalities of brain function during the resting state in chronic pain. To this end, we performed state-of-the-art analyses of oscillatory brain activity, brain connectivity, and brain networks in 101 patients of either sex suffering from chronic pain. The results show that global and local measures of brain activity did not differ between chronic pain patients and a healthy control group. However, we observed significantly increased connectivity at theta (4-8 Hz) and gamma (>60 Hz) frequencies in frontal brain areas as well as global network reorganization at gamma frequencies in chronic pain patients. Furthermore, a machine learning algorithm could differentiate between patients and healthy controls with an above-chance accuracy of 57%, mostly based on frontal connectivity. These results suggest that increased theta and gamma synchrony in frontal brain areas are involved in the pathophysiology of chronic pain. Although substantial challenges concerning the reproducibility of the findings and the accuracy, specificity, and validity of potential electroencephalography-based disease markers remain to be overcome, our study indicates that abnormal frontal synchrony at theta and gamma frequencies might be promising targets for noninvasive brain stimulation and/or neurofeedback approaches.

Chronic pain patients suffer from more than just pain; depression and anxiety, sleep disturbances, and decision-making abnormalities (Apkarian et al., 2004a) also significantly diminish their quality of life. Recent studies have demonstrated that chronic pain harms cortical areas unrelated to pain (Apkarian et al., 2004b; Acerra and Moseley, 2005), but whether these structural impairments and behavioral deficits are connected by a single mechanism is as of yet unknown. Here we propose that long-term pain alters the functional connectivity of cortical regions known to be active at rest, i.e., the components of the "default mode network" (DMN). This DMN (Raichle et al., 2001; Greicius et al., 2003; Vincent et al., 2007) is marked by balanced positive and negative correlations between activity in component brain regions. In several disorders, however this balance is disrupted (Fox and Raichle, 2007). Using well validated functional magnetic resonance imaging (fMRI) paradigms to study the DMN (Fox et al., 2005), we investigated whether the impairments of chronic pain patients could be rooted in disturbed DMN dynamics. Studying with fMRI a group of chronic back pain (CBP) patients and healthy controls while executing a simple visual attention task, we discovered that CBP patients, despite performing the task equally well as controls, displayed reduced deactivation in several key DMN regions. These findings demonstrate that chronic pain has a widespread impact on overall brain function, and suggest that disruptions of the DMN may underlie the cognitive and behavioral impairments accompanying chronic pain.

Chronic pain and narcotics: a dilemma for primary care.

Rumination is a form of thought characterized by repetitive focus on discomforting emotions or stimuli. In chronic pain disorders, rumination can impede treatment efficacy. The brain mechanisms underlying rumination about chronic pain are not understood. Interestingly, a link between rumination and functional connectivity (FC) of the brain's default mode network (DMN) has been identified within the context of mood disorders. We, and others, have also found DMN dysfunction in chronic pain populations. The medial prefrontal cortex (mPFC) is a key node of the DMN that is anatomically connected with the descending pain modulatory system. Therefore, we tested the hypothesis that in patients with chronic pain, the mPFC exhibits abnormal FC related to the patient's degree of rumination about their pain. Seventeen patients with idiopathic temporomandibular disorder (TMD) and 17 age- and sex-matched healthy controls underwent resting state functional MRI, and rumination about pain was assessed through the rumination subscale of the Pain Catastrophizing Scale. Compared with healthy controls, we found that TMD patients exhibited enhanced mPFC FC with other DMN regions, including the posterior cingulate cortex (PCC)/precuneus (PCu) and retrosplenial cortex. We also found that individual differences in pain rumination in the chronic pain patients (but not in healthy controls) were positively correlated to mPFC FC with the PCC/PCu, retrosplenial cortex, medial thalamus, and periaqueductal/periventricular gray. These data implicate communication within the DMN and of the DMN with the descending modulatory system as a mechanism underlying the degree to which patients ruminate about their chronic pain.

P23-T Altered functional connectivity in trigeminal neuralgia

Driving functions in a video simulator in chronic non-malignant pain patients using and not using codeine

We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks ["external-task positive" and "default-mode network" (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance.

Perceived self-efficacy is a non-negligible outcome when measuring the impact of self-management interventions for chronic pain patients. However, no validated, chronic pain-specific self-efficacy scales exist for studies conducted with French-speaking populations. To establish the validity of the use of the French-Canadian Chronic Pain Self-efficacy Scale (FC-CPSES) among chronic pain patients. The Chronic Disease Self-Efficacy Scale is a validated 33-item self-administered questionnaire that measures perceived self-efficacy to perform self-management behaviours, manage chronic disease in general and achieve outcomes (a six-item version is also available). This scale was adapted to the context of chronic pain patients following cross-cultural adaptation guidelines. The FC-CPSES was administered to 109&nbsp;fibromyalgia and 34 chronic low back pain patients (n=143) who participated in an evidence-based self-management intervention (the PASSAGE program) offered in 10 health care centres across the province of Quebec. Cronbach's alpha coefficients (α) were calculated to determine the internal consistency of the 33- and six-item versions of the FC-CPSES. With regard to convergent construct validity, the association between the FC-CPSES baseline scores and related clinical outcomes was examined. With regard to the scale's sensitivity to change, pre- and postintervention FC-CPSES scores were compared. Internal consistency was high for both versions of the FC-CPSES (α=0.86 to α=0.96). Higher self-efficacy was significantly associated with higher mental health-related quality of life and lower pain intensity and catastrophizing (P<0.05), supporting convergent validity of the scale. There was a statistically significant increase in FC-CPSES scores between pre- and postintervention measures for both versions of the FC-CPSES (P<0.003), which supports their sensitivity to clinical change during an intervention. These data suggest that both versions of the FC-CPSES are reliable and valid for the measurement of pain management self-efficacy among chronic pain patients.

Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.

There have been a few open-label nonplacebo reports on the successful use of lidocaine 5% patch (L5P) for other types of pain besides postherpetic neuralgia, such as chronic low back pain. With the these reports, we began to utilize L5P routinely for chronic pain patients (CPPs) with various pain diagnoses. The purpose of this report was to describe the results of a retrospective review of this open-label naturalistic L5P chronic pain treatment trial and to attempt to delineate predictors of perceived clinical response. Consecutive CPPs were selected for this clinical trial according to the following inclusion criteria: the CPPs with pain greater than 6-month duration and either a hyperalgesic pain area or trigger point, which could be covered by one L5P, were offered a 3-day L5P naturalistic treatment trial. The purpose of this trial was to determine which CPPs would perceive improvement and continue using L5P. CPPs entering the trial completed the neuropathic pain scale (NPS) at entrance and completion of the trial. The senior author also completed a baseline information tool on each CPP entering this naturalistic trial. At the completion of the 3-day trial, the CPPs were asked if they perceived pain improvement with the use of L5P. In the retrospective review, the CPPs were thus segregated into two groups, those with and without perceived clinical improvement, and were statistically compared for available clinical variables. Logistic regression was then utilized to determine which significant independent variables contributed to the correct prediction of perceived improvement. Multidisciplinary pain facility. Patients with chronic pain. Of 362 consecutive CPPs, 114 or 31.5% were deemed candidates for this naturalistic trial. None of the CPPs refused or fulfilled exclusion criteria eliminating them from the trial. The total sample (N = 114) showed statistical improvement on all 10 NPS scales (except scales 4 and 6) plus the NPS 4, NPS nonallodynic 8, and NPS 10. The perceived clinically improved group (N = 87, 76.3% of those entering the trial), also showed perceived improvement on all preceding scales except 4 and 6. The perceived clinically nonimproved group (N = 27, 23.7% of those entering the trial) showed statistical improvement on scales B and NPS 10. Perceived improvement was predicted by the following variables: pain wakes patient up, patch placement not low back, and not in litigation. These variables explained 9.8%, 20%, and 14% of the variance, respectively. Overall, 44.5% of the variance was explained. A significant percentage of CPPs exposed to an L5P 3-day naturalistic trial perceived clinical improvement. However, this can only be concluded as an initial effect, and whether or not this effect is attributable to L5P cannot be derived from our data as the effect could have been nonspecific. The apparent CPP perceived clinical improvement was not associated with any particular useful clinical indicator. As such, at present, no variable can be recommended for use in selecting CPPs for such a naturalistic L5P clinical treatment trial. However, this study indicates that such a trial can be useful in selecting CPPs who may perceive benefit from L5P.

Chronic pain and substance use disorders frequently co-occur. Indeed, chronic pain is highly prevalent, affecting 23–68% of patients receiving opioid agonist treatments (OAT) worldwide. The majority of available estimates come from American studies, but data are still lacking in Europe. We aim to provide European estimates of the prevalence of chronic pain in patients receiving OAT using French data, since France is the first European country in terms of number of patients with OAT. The secondary objectives were to characterize the features and management of chronic pain, as well identify associated risk factors. We conducted a multicenter, cross-sectional study, recruiting patients treated either with buprenorphine or methadone in 19 French addiction centers, from May to July 2016. All participants had to complete a semi-directed questionnaire that collected sociodemographic and medical data, pain characteristics, and licit or illicit drug consumption. In total, 509 patients were included. The prevalence of chronic pain was estimated at 33.2% (95% CI: 29.1–37.3). Compared to non-chronic pain patients, chronic pain patients were older (38.4 vs. 36.1 years, p = 0.006), were more unemployed (66 vs. 52%, p = 0.003), had more psychiatric comorbidities (50 vs. 39%, p = 0.02), and split their OAT for pain management more frequently (24 vs. 7%, p = 0.009). Pain intensity was moderate or severe in 75% of chronic pain patients. Among patients with chronic pain, 15.4% were not prescribed, and did not self-medicate with, any analgesic drugs, 52.1% were prescribed analgesics (non-opioid analgesics, 76.3%; codeine, tramadol, opium, 27.2%; and morphine, fentanyl, oxycodone, 11.8%), and 32.5% exclusively self-medicated with analgesics. Moreover, 20.1% of patients with chronic pain also used illicit drugs for pain relief. On multivariate analysis, variables that remained significantly associated with chronic pain were age [OR = 1.03 (95% CI: 1.00–1.05], p = 0.02], anxiety [OR = 1.52 (1.15–2.02), p = 0.003], and depression [OR = 1.25 (1.00–1.55), p = 0.05]. Chronic pain is a highly prevalent condition in patients receiving OAT, and its appropriate management remains uncertain, since insufficient relief and frequent additional self-medications with analgesics or illicit drugs were reported by these patients. Increased awareness among caregivers is urgently needed regarding a systematic and careful assessment, along with an adequate management of chronic pain in patients receiving OAT.

Compared self-concepts of three groups, medical patients, chronic low back pain patients and chronic head pain patients (N = 60) to determine (1) whether chronic pain patients have self-perceptions that differ from other medical patients; (2) whether changes in self-perception are limited to physical attributes and capacities; and finally (3) whether persons who suffer different types of chronic pain would have differing self-concepts. Significantly lower self-concepts were obtained from groups of head pain and low back pain patients. Self-concept patterns for the two pain groups were quite similar with the exception of two self-concept components that were significantly lower for the head pain group. Differences were explained in terms of loss of many normal functions and disruption of normal life-styles. Implications for treatment of pain patients and for training of health professionals were discussed.

Chronic pain is associated with anhedonia and decreased motivation. These behavioral alterations have been linked to alterations in the limbic brain and could explain the increased risk for obesity in pain patients. The mechanism of these behavioral changes and how they set in in relation to the development of chronic pain remain however poorly understood. Here we asked how eating behavior was affected in low-back pain patients before and after they transitioned to chronic pain, compared to patients whose pain subsided. Additionally, we assessed how the hedonic perception of fat-rich food, which is altered in chronic pain patients, related to the properties of the nucleus accumbens in this patients' population. We hypothesized that the accumbens would be directly implicated in the hedonic processing of fat-rich food in pain patients because of its well-established role in hedonic feeding and fat ingestion, and its emerging role in chronic pain. Accordingly, we used behavioral assays and structural brain imaging to test sub-acute back pain patients (SBP) and healthy control subjects at baseline and at approximately one-year follow-up. We also studied a sample of chronic low-back pain patients (CLBP) at one time point only. We found that SBP patients who recovered at follow-up (SBPr) and CLBP patients showed disrupted eating behaviors. In contrast, SBP patients who persisted in having pain at follow-up (SBPp) showed intact eating behavior. From a neurological standpoint, only SBPp and CLBP patients showed a strong and direct relationship between hedonic perception of fat-rich food and nucleus accumbens volume. This suggests that accumbens alterations observed in SBPp patients in previous works might protect them from hedonic eating disruptions during the early course of the illness. We conclude that disrupted eating behavior specifically sets in after pain chronification and is accompanied by structural changes in the nucleus accumbens.

Resilience is a psychological trait that strongly predicts chronic pain-related health outcomes. The neural correlates of both pain and trait resilience are critical to understand the brain-behaviour relationship in chronic pain; yet, neural correlates of resilience in chronic pain states are unknown. However, measures of pain perception and a wide range of psychological health measures have been linked to function of the default mode network (DMN). Thus, we aimed to determine the relationships between resilience, pain perception, and functional connectivity (FC) within the DMN and between the DMN and other brain networks. Resting-state functional magnetic resonance imaging data were acquired from 51 chronic pain patients with a form of spondylarthritis (ankylosing spondylitis) and 51 healthy control participants. Participants completed a questionnaire on their individual trait resilience (the Resilience Scale), and patients reported their clinical pain. In healthy controls, we found within-DMN FC to be stronger in less resilient individuals. In patients with chronic pain, individual resilience was negatively correlated with pain and disease activity. Cross-network FC between the DMN and the sensorimotor network was abnormally high in patients with high clinical pain scores on the day of the study. Finally, there was an interaction between within-DMN FC and clinical pain report in patients: In patients reporting greater pain, the relationship between within-DMN connectivity and resilience was atypical. Thus, our findings reveal different neural representations of resilience and pain. The way in which these behavioural measures interact provides insight into understanding the neural correlates of chronic pain.

Physical fitness and chronic low back pain: A case-control study including 517 individuals