Pain
-
Randomized Controlled Trial
Noninvasive targeted modulation of pain circuits with focused ultrasonic waves.
Direct interventions into deep brain circuits constitute promising treatment modalities for chronic pain. Cingulotomy and deep brain stimulation targeting the anterior cingulate cortex have shown notable improvements in the unpleasantness of pain, but these interventions require brain surgeries. In this study, we have developed an approach that can modulate this deep brain affective hub entirely noninvasively, using low-intensity transcranial-focused ultrasound. ⋯ The stimulation was well tolerated, and no adverse events were detected. Side effects were generally mild and resolved within 24 hours. Together, the direct, ultrasonic stimulation of the anterior cingulate cortex offers rapid, clinically meaningful, and durable improvements in pain severity.
-
Preclinical and clinical work has demonstrated altered plasticity and activity in the nucleus accumbens (NAc) under chronic pain states, highlighting critical therapeutic avenues for the management of chronic pain conditions. In this study, we demonstrate that myocyte enhancer factor 2C (MEF2C), a master regulator of neuronal activity and plasticity, is repressed in NAc neurons after prolonged spared nerve injury (SNI). ⋯ Transcriptional changes induced by Mef2c overexpression were different than those observed after desipramine treatment, suggesting a mechanism of action different from antidepressants. Overall, we show that interventions in MEF2C-regulated mechanisms in the NAc are sufficient to disrupt the maintenance of chronic pain states, providing potential new treatment avenues for neuropathic pain.
-
While interdisciplinary multimodal pain treatment (IMPT) is an effective treatment option for chronic low back pain, it is usually accomplished as an inpatient treatment incurring substantial healthcare costs. Day hospital IMPT could be a resource-saving alternative approach, but whether treatment setting is associated with differences in treatment outcomes has not yet been studied. In a retrospective matched cohort study including data from N = 595 patients diagnosed with chronic back pain and undergoing IMPT at the back pain center in Essen, Germany, we investigated the association between treatment setting (ie, inpatient or day patient of an otherwise identical IMPT) and pain intensity, disability, and self-efficacy after treatment. ⋯ Moreover, day patients achieved higher scores in pain-related self-efficacy at discharge, 3- and 6-month post-IMPT (d = 0.62, 0.99, and 1.21, respectively) and reported fewer incapacity-for-work days than inpatients at 6-month post-IMPT (d = 0.45). These data suggest that day hospital IMPT can be as effective as inpatient treatment and might even be more effective for the less afflicted patients. Further research regarding treatment setting and indication could guide optimized and cost-efficient treatments that are more closely tailored to the individual patient's needs.
-
Patients with temporomandibular disorders (TMDs) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we used in vivo GCaMP3 Ca 2+ imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neurons in vivo, specifically in mouse models of TMJ injury and inflammation. ⋯ In addition, we confirmed the attenuating effect of calcitonin gene-related peptide antagonist on FMO-induced sensitization by in vivo GCaMP3 Ca 2+ imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain, bringing us closer to understanding the pathophysiological processes underlying TMJ pain after TMJ injury. Our study also illustrates the utility of in vivo GCaMP3 Ca 2+ imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMJ pain.
-
The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene ( COMT ) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial results on its role in fibromyalgia (FM). Here, the SNP Val158Met was analyzed in 294 FM patients (without comorbidities) and 209 healthy controls (without chronic pain). ⋯ However, considering only the FM patient group, the A/A homozygous genotype was significantly associated with severe pain intensity ( P = 0.007). This study highlighted associations between the SNP Val158Met and both FM and pain intensity, suggesting a link between dopaminergic dysfunction and vulnerability to chronic pain. Further studies should explore this SNP in FM patients in conjunction with COMT enzymatic activity and other symptoms connected with the dopaminergic system such as depression or sleep impairment.