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Pain remains a global health challenge. For decades, clinicians have been primarily relying on μ-opioid receptor (MOR) agonists and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management. MOR agonists remain the most efficacious analgesics available; however, adverse effects related to MOR agonists use are severe which often lead to forced drug discontinuation and inadequate pain relief. The recent opioid overdose epidemic urges the development of safer analgesics. Combination therapy is a well-established clinical pharmacotherapeutic strategy for the treatment of various clinical disorders. The combination of MOR agonists with non-MOR agonists may increase the analgesic potency of MOR agonists, reduce the development of tolerance and dependence, reduce the diversion and abuse, overdose, and reduce other clinically significant side effects associated with prolonged opioid use such as constipation. Overall, the combination therapy approach could substantially improve the therapeutic profile of MOR agonists. This review summarizes some recent developments in this field.
Learn More >Pain resulting from cancer metastatic to bone is a major clinical problemVascular endothelial growth factor receptors are involved in tumor angiogenesis and are felt to be analgesic targets WHAT THIS ARTICLE TELLS US THAT IS NEW: In a female rat model of metastatic breast cancer, expression of vascular endothelial growth factor A and its receptor vascular endothelial growth factor receptor 2 were up-regulated in spinal tissueBlocking vascular endothelial growth factor signaling improved several measures of nociception and function in this model suggesting a role for vascular endothelial growth factor antagonists in reducing cancer-related pain BACKGROUND:: Cancer pain is a pervasive clinical symptom impairing life quality. Vascular endothelial growth factor A has been well studied in tumor angiogenesis and is recognized as a therapeutic target for anti-cancer treatment. This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization.
Learn More >Shoulder pain is a common condition associated with slow recovery and high recurrence rates. Persistent pain may lead to structural brain changes that may further promote pain chronification. The present study addressed whether abnormal changes in cortical surface structure exist in patients with chronic shoulder pain of myofascial origin and whether such changes would be related to pain measures. Brain structural MRIs were obtained in 22 patients with chronic pain in the bilateral upper trapezius muscles and in 22 healthy controls. Cortical thickness, gyrification index and sulcal depth were assesses together with pain measures. Shallower sulcal depth was found in patients in the right central sulcus, posterior insula, inferior frontal and dorsomedial prefrontal cortices, precuneus, and the middle temporal cortex, and in the left medial orbitofrontal cortex. Negative correlations were found between the right central sulcus and pain intensity and between the left medial orbitofrontal cortex and pain affect. Cortical thickness or gyrification index did not differ significantly between the two groups. The afflicted cortical regions constitute interacting networks responsible for sensory, affective and cognitive dimensions of the pain experience.
Learn More >Non-specific chronic low back pain (NSCLBP) patients present with reduced back extensor muscle endurance which could be explained by the higher fatigability of their lumbar muscles. However, studies investigating lumbar muscle fatigability have shown contradictory findings. Furthermore, none investigated potential asymmetry in lumbar muscle fatigability, despite neuromuscular asymmetry being reported as a risk factor for NSCLBP. The present study's primary purpose was to determine whether NSCLBP patients presented with higher lumbar muscle fatigability and fatigability asymmetry than asymptomatic participants.
Learn More >This study evaluated suicidality and its risk factors in patients with tension-type headache (TTH). We recruited new patients with TTH who visited general hospitals. We recorded their clinical characteristics and conducted the Headache Impact Test-6 (HIT-6) and the Insomnia Severity Index (ISI) for assessment. We also interviewed the patients to identify major depressive disorder (MDD), generalized anxiety disorder (GAD), and suicidality with the Mini International Neuropsychiatric Interview-Plus Version 5.0.0 (MINI). The frequency of suicidality was compared between TTH patients and healthy controls. Major risk factors for suicidality were also determined. A total of 332 TTH patients with the same number of healthy controls were recruited from five general hospitals. Suicidality was observed in 82 (24.7%) TTH patients. The frequency of suicidality was significantly higher in patients with TTH than in the controls. Furthermore, the frequency of suicidality was higher in patients with chronic TTH (CTTH) than in the controls. The major risk factors for suicidality were MDD, GAD, a low education level, insomnia, chronicity of TTH, and pericranial tenderness. Suicidal ideation or attempt seems to be a common feature in TTH. Therefore, it is important to identify risk factors related to suicidality in TTH patients, which may help reduce suicidality.
Learn More >Our knowledge of central sensitization (CS) in chronic low back pain (CLBP) is limited. 2011 fibromyalgia criteria and severity scales (2011 FM survey) has been used to determine FM positive as a surrogate of CS. The major features of CS including widespread hyperalgesia and dysfunction of the descending inhibitory pathways can be identified by pressure pain threshold (PPT) and conditioned pain modulation (CPM) tests. The purpose of the study was to examine neurophysiological characteristics and psychosocial symptoms in a subgroup of FM positive CLBP compared to FM negative CLBP patients.
Learn More >Uremic pruritus with elevated levels of calcium phosphate (CaP) in skin is a common symptom in patients with chronic kidney disease (CKD). In this study, we demonstrate that intradermal injection of CaP into mice-triggered scratching by up-regulating the IL-6 in skin and phosphorylation of ERKs in dorsal root ganglion (DRG) in a dose-dependent manner. IL-6 is essential because the CaP-induced up-regulation of phosphorylated (p)-ERK in DRG was considerably reduced in the IL-6 knockout mice. Microarray analysis in conjunction with real-time PCR revealed a higher mRNA expression of Bruton's tyrosine kinase (BTK) gene in DRG after CaP injection. The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice. A high amount of IL-6 was detected in itchy skin and blood of patients with CKD. The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib. The mechanism by which the CaP-induced pruritus mediated by the IL-6/p-BTK/p-ERK signaling was revealed.-Keshari, S., Sipayung, A. D., Hsieh, C.-C., Su, L.-J., Chiang, Y.-R., Chang, H.-C., Yang, W.-C., Chuang, T.-H., Chen, C.-L., Huang, C.-M. The IL-6/p-BTK/p-ERK signaling mediates the calcium phosphate-induced pruritus.
Learn More >The marked increase in deaths related to opioid drugs since 1999 was associated with an increase in the number of prescriptions for opioid drugs. This was accompanied by increasing demand for improved management of chronically painful conditions. These factors suggest that improvements are needed in the education of physicians with regard to the management of chronic pain, the optimal therapeutic application of opioid drugs, and the avoidance of substance use disorders. In this paper we address the evidence that physician education can influence prescribing practices and discuss approaches to enhancing the pre-clinical and clinical education of medical students in pain management and substance use disorders. SIGNIFICANCE STATEMENT: N/A.
Learn More >Patients qualifying for Medicare disability have the highest rates of opioid use compared with older Medicare beneficiaries and commercial insurance beneficiaries. Research on opioid overdose deaths in this population can help identify appropriate interventions.
Learn More >Individuals with chronic pain commonly report significant functional impairment and reduced quality of life. Despite this, little is known about psychological processes and mechanisms underpinning enhancements in well-being within this population. The study aimed to investigate whether (1) increased levels of pain intensity and interference were associated with lower levels of mental well-being, (2) increased positive goal engagement was associated with higher levels of mental well-being and (3) whether the relationships between pain characteristics and mental well-being were mediated by increased positive goal engagement. A total of 586 individuals with chronic pain participated in the cross-sectional, online study. Participants completed self-report measures to assess pain intensity and interference, mental well-being and goal motivation variables. Results showed that pain interference and positive goal engagement were associated with mental well-being. Moreover, the relationship between pain interference and mental well-being was partially mediated by positive goal engagement. The results provide tentative evidence for the protective role of positive goal engagement in enabling individuals with chronic pain to maintain a sense of mental well-being. The study develops the biopsychosocial model of chronic pain by examining the roles and relationships of relevant yet previously unexplored psychological constructs. The promotion of mental well-being through the enhancement of positive goal engagement is discussed, offering a platform for further research and clinical interventions.
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