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acute treatment of migraine in real-world settings, both as a standalone replacement of pharmaceuticals, as well as an adjunct to medications.Background Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain. Methods EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists. Results A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors. Conclusions This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 may play a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.Acute pain serves as a protective mechanism that alerts us to potential tissue damage and drives a behavioural response that removes us from danger. The neural circuitry critical for mounting this behavioural response is situated within the brainstem and is also crucial for producing analgesic and hyperalgesic responses. In particular, the periaqueductal grey, rostral ventromedial medulla, locus coeruleus and subnucleus reticularis dorsalis are important structures that directly or indirectly modulate nociceptive transmission at the primary nociceptive synapse. Substantial evidence from experimental animal studies suggests that plasticity within this system contributes to the initiation and/or maintenance of chronic neuropathic pain, and may even predispose individuals to developing chronic pain. Indeed, overwhelming evidence indicates that plasticity within this circuitry favours pro-nociception at the primary synapse in neuropathic pain conditions, a process that ultimately contributes to a hyperalgesic stavide an overview of the human brain imaging investigations that have improved our understanding of the pain-modulation system in acute pain states and in neuropathic conditions. Our interpretation of the findings from these studies is often guided by the existing body of experimental animal literature, in addition to evidence from psychophysical investigations. Overall, understanding the plasticity of this system in human neuropathic pain conditions alongside the existing experimental animal literature will ultimately improve treatment options.Pediatric chronic orofacial pain (OFP) is an umbrella term which refers to pain associated with the hard and soft tissues of the head, face, and neck lasting >3 months in patients younger than 18 years of age. Common chronic pediatric OFP diagnoses include temporomandibular disorder, headaches, and neuropathic pain. Chronic OFP can adversely affect youth's daily functioning and development in many areas of well-being, and may be associated with emotional stress, depression, functional avoidance, and poor sleep, among other negative outcomes. In this mini-review, we will discuss common psychological comorbidities and familial factors that often accompany chronic pediatric OFP conditions. We will also discuss traditional management approaches for pediatric orofacial pain including education, occlusal appliances, and psychological treatments such as relaxation, mindfulness-based interventions, and cognitive-behavioral treatments. Finally, we highlight avenues for future research, as a better understanding of chronic OFP comorbidities in childhood has the potential to prevent long-term pain-related disability in adulthood.Glial cells play an essential role in maintaining the proper functioning of the nervous system. They are more abundant than neurons in most neural tissues and provide metabolic and catabolic regulation, maintaining the homeostatic balance at the synapse. Chronic pain is generated and sustained by the disruption of glia-mediated processes in the central nervous system resulting in unbalanced neuron-glial interactions. Animal models of neuropathic pain have been used to demonstrate that changes in immune and neuroinflammatory processes occur in the course of pain chronification. Spinal cord stimulation (SCS) is an electrical neuromodulation therapy proven safe and effective for treating intractable chronic pain. Traditional SCS therapies were developed based on the gate control theory of pain and rely on stimulating large Aβ neurons to induce paresthesia in the painful dermatome intended to mask nociceptive input carried out by small sensory neurons. A paradigm shift was introduced with SCS treatments that do n while modulating them toward expression levels of healthy animals. The ability of DTMP to modulate key genes and proteins involved in glia-mediated processes affected by pain toward levels found in uninjured animals demonstrates a shift in the neuron-glial environment promoting analgesia.Approximately 100 million adults in the United States have chronic pain, though only a subset utilizes the vast majority of healthcare resources. Multidisciplinary care has been shown to improve outcomes in a variety of clinical conditions. There is concern that multidisciplinary care of chronic pain patients may overwhelm existing resources and increase healthcare utilization due to the volume of patients and the complexity of care. We report our findings on the use of multidisciplinary conferences (MDC) to facilitate care for the most complex patients seen at our tertiary center. Thirty-two of nearly 2,000 patients seen per year were discussed at the MDC, making up the top 2% of complex patients in our practice. We evaluated patients' numeric rating score (NRS) of pain, medication use, hospitalizations, emergency department visits, and visits to pain specialists prior to their enrollment in MDC and 1 year later. Matched samples were compared using Wilcoxon's signed rank test. Patients' NRS scores significantly decreased from 7.64 to 5.54 after inclusion in MDC (p less then 0.001). A significant decrease in clinic visits (p less then 0.001) and healthcare utilization (p less then 0.05) was also observed. Opioid and non-opioid prescriptions did not change significantly (p = 0.43). 83% of providers agreed that MDC improved patient care. While previous studies have shown the effect of multi-disciplinary care, we show notable improvements with a team established around a once-a-month MDC.Introduction Effective clinical care for chronic pain requires accurate, comprehensive, meaningful pain assessment. This study investigated healthcare providers' perspectives on seven pain measurement indices for capturing pain intensity. Methods Semi-structured telephone interviews were conducted with a purposeful sample from four US regions of 20 healthcare providers who treat patients with chronic pain. The qualitative interview guide included open-ended questions to address perspectives on pain measurement, and included quantitative ratings of the importance of seven indices [average pain, worst pain, least pain, time in no/low pain, time in high pain, fluctuating pain, unpredictable pain]. Qualitative interview data were read, coded and analyzed for themes and final interpretation. Standard quantitative methods were used to analyze index importance ratings. Results Despite concerns regarding 10-point visual analog and numeric rating scales, almost all providers used them. Providers most commonly asked about average pain, although they expressed misgivings about patient reporting and the index's informational value. Some supplemented average with worst and least pain, and most believed pain intensity is best understood within the context of patient functioning. Worst pain received the highest mean importance rating (7.60), average pain the second lowest rating (5.65), and unpredictable pain the lowest rating (5.20). Discussion Assessing average pain intensity obviates obtaining clinical insight into daily contextual factors relating to pain and functioning. Pain index use, together with timing, functionality and disability, may be most effective for understanding the meaning to patients of high pain, how pain affects their life, how life affects their pain, and how pain changes and responds to treatment.Introduction Clumsiness has been described as a symptom associated with neck pain and injury. However, the actuality of this symptom in clinical practice is unclear. The aim of this investigation was to collect definitions and frequency of reports of clumsiness in clinical studies of neck pain/injury, identify objective measures of clumsiness and investigate the association between the neck and objective measures of clumsiness. Methods Six electronic databases were systematically searched, records identified and assessed including a risk of bias. Heterogeneity in designs of studies prevented pooling of data, so qualitative analysis was undertaken. Results Eighteen studies were retrieved and assessed; the overall quality of evidence was moderate to high. Eight were prospective cross-sectional studies comparing upper limb sensorimotor task performance and ten were case series involving a healthy cohort only. Clumsiness was defined as a deficit in coordination or impairment of upper limb kinesthesia. All but one of 18 studies found a deterioration in performing upper limb kinesthetic tasks including a healthy cohort where participants were exposed to a natural neck intervention that required the neck to function toward extreme limits. Conclusion Alterations in neck sensory input occurring as a result of requiring the neck to operate near the end of its functional range in healthy people and in patients with neck pain/injury are associated with reductions in acuity of upper limb kinesthetic sense and deterioration in sensorimotor performance. Understanding the association between the neck and decreased accuracy of upper limb kinesthetic tasks provide pathways for treatment and rehabilitation strategies in managing clumsiness.Background Bone cancer pain (BCP) significantly affects patient quality of life, results in great bodily and emotional pain, and creates difficulties in follow-up treatment and normal life. Transient receptor potential ankyrin 1 (TRPA1) is an essential transduction ion channel related to neuropathic and inflammatory pain. However, the role of TRPA1 in BCP remains poorly understood. This study aimed to explore the relationship between TRPA1 and BCP. Methods A BCP model was induced by Walker256 cells to the left tibia. The sham group was induced by normal saline to the left tibia. Thereafter, pain behaviors and TRPA1 expression between the BCP group and the sham group were observed on the 14th day of modeling. compound library chemical The TRPA1 antagonist A967079 (10 mg/kg) was injected via tail vein. TRPA1 antisense oligodeoxynucleotide (AS-ODN, 5 nmol/10 μl) and missense oligodeoxynucleotide (MS-ODN, 5 nmol/10 μl) were intrathecally delivered via a mini-osmotic pump for 5 consecutive days to assess the effect of TRPA1 on BCP. Behavioral tests were assessed preoperatively and postoperatively.

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