Rejected

CXCR3 is a well-known receptor involved in immune cell recruitment and inflammation. Pathological inflammation leads to pain stimulation and hence nociception. Therefore, we decided to review the recent research on CXCR3 to identify its precise role in the modulation of pain in a variety of clinical conditions targeting various regions of the body. Studies were selected from PubMed Medline, which relate CXCR3 to the progression of diseases with either bone cancer pain, neuropathic pain, cystitis pain, osteoarthritis and rheumatoid arthritis pain, dental pain, in particular, periodontitis and pulpitis. In all the diseases studied, a high prevalence of CXCR3 and/or its ligand were identified where CXCR3 is a key player in the pathophysiological process of many inflammatory conditions. CXCR3 and its ligands, particularly CXCL10, modulate nociception via actions in the dorsal root ganglia and dorsal horn of the spinal cord, in cases of bone cancer pain, neuropathic, and joint pain. However, with the other studied disease, no direct link to pain has been made, although it contributes to the pathological progression of the diseases and hence would be a causal factor for the pain. Furthermore, CXCR3 appears to play a role in desensitizing the opioid receptor in the descending modulatory pathway within the brain stem as well as modulating opioid-induced hyperalgesia in the dorsal horn of the spinal cord. Further research is required for understanding the exact mechanisms of CXCR3 in pain modulation centrally and peripherally. A greater understanding of the immunological activities and pharmacological consequence of CXCR3 and its ligands could help in the discovery of newer drugs for modulating pain arising from pathogenic or inflammatory sources. Given the significance of the CXCR3 for nociception, its utilization may prove to be beneficial as a target for analgesia.

The purpose of this study was to compare the effects of combined epidural-general anesthesia with those of general anesthesia alone on hemodynamic instability (intraoperative hypotension and hypertensive crisis) during pheochromocytoma and sympathetic paraganglioma surgery. A total of 119 patients' medical records were reviewed who were diagnosed as having pheochromocytoma and sympathetic paraganglioma on the basis of histological findings. Intraoperative hypotension was defined as a mean blood pressure < 60 mmHg or a decrease > 30% in baseline systolic blood pressure after adrenal vein ligation. Hypertensive crisis was defined as a systolic blood pressure > 200 mmHg or an increase > 30% in baseline systolic blood pressure during the operation. The predictor variables for intraoperative hypotension and hypertensive crisis were analyzed with logistic regression models. Data were presented as adjusted odds ratio with 95% confidence interval. The independent predictors of intraoperative hypotension were an increased attenuation number on unenhanced computed tomography (1.112 [1.009-1.226], p = 0.033), a high baseline mean blood pressure (1.063 [1.012-1.117], p = 0.015), and the combined epidural-general anesthesia (5.439 [1.410-20.977], p = 0.014). In contrast, an increased attenuation number on unenhanced computed tomography was the only independent predictor of hypertensive crisis (1.087 [1.021-1.158], p = 0.009). The combined epidural-general anesthesia was not effective in attenuating hypertensive responses, but could have exacerbated intraoperative hypotension. These findings should be taken into account before selecting the anesthetic technique in pheochromocytoma and sympathetic paraganglioma surgery.

Mirogabalin was recently approved in Japan for the treatment of peripheral neuropathic pain, based on data from clinical trials in diabetic peripheral neuropathic pain (DPNP) and post-herpetic neuralgia (PHN), common clinical conditions which cause intense distress for patients. We characterized the safety and tolerability of mirogabalin in Japanese patients with renal impairment.

Allergic contact dermatitis (ACD) is characterized by itching, skin inflammation, and allergic responses caused by release of immunoglobulin E and T helper 2-specific cytokines. The aim of this study is to investigate the ameliorative and synergic effects of herbal formula, Derma-H, containing Fisch. ex Bunge (AM) and Benth (NT) which have been used as traditional medicinal herbs for the cure of dryness, edema, and pruritus. 2,4-Dinitrochlorobenzene (DNCB) was applied for ACD induction. AM, NT, and a mixture of AM and NT was topically applied to skin lesions for 11 days. Dermatitis score and number of scratches were significantly diminished in AM, NT, and AM + NT (Derma-H)-treated groups. Especially, Derma-H was more effective than single treatment of AM and NT on skin hyperplasia and mast cell infiltration. Also, NGF expression decreased by NT and a mixture of AM and NT. Additionally, series of TrkA, Raf-1, MEK, and ERK were significantly inhibited by topical AM and NT application. Those findings suggested AM and NT treatment has a synergic effect on DNCB-induced ACD in mice.

Chronic neuropathic pain (CNP) is a common condition cancer survivors experience. Mindfulness training may be one approach to address the psychosocial factors associated with CNP. The purpose of this study was to understand patients' experiences in an 8-week online mindfulness-based program (MBP), including techniques and skills learned and applied, barriers to practice, and research experiences.

Migraine is the most common chronic neurological disease. Migraine is in the top 5 causes that reduce the quality of life. In recent years, neuromodulation techniques are successfully used with primary headaches. Several variants of non-invasive neuromodulation have been shown to be effective in various forms of migraine. This review analyzes clinical trials and case reports of the effectiveness and safety of non-invasive stimulation of the first branch of the trigeminal nerve in migraine.

The use of epidural analgesia after major surgery is a well-established analgesia method. Epidural analgesia for postoperative pain relief needs to be monitored regularly in order to evaluate patient satisfaction and avoid side effects. However, due to the new available regional techniques, the role of epidural analgesia is being questioned and data about patient satisfaction is lacking. The current study was designed to evaluate patient satisfaction with epidural analgesia, its efficacy and reasons for premature termination of epidural analgesia.

Feline chronic gingivostomatitis (FCGS) is an immune-mediated inflammatory condition affecting the oral mucosa that results in substantial pain and suffering. The goal of this study was to complete an in-depth immunohistochemistry analysis of affected FCGS mucosa, to perform and compare immune cell phenotypes in the blood of FCGS and healthy controls cats, and to determine a transcriptomic profile of the affected and normal oral mucosa of FCGS cats. We hypothesized that cats with FCGS would have circulating activated CD8+ T cells and that tissues would be infiltrated with activated B and T cells with a highly proinflammatory transcriptome. We found that oral mucosal tissues from cats with FCGS have high tissue infiltration of B cells and that T cells include both CD4+ and CD8+ lymphocytes. Cells positive for CD25 (IL2 receptor, indicative of lymphocyte activation) and FOXP3 (indicative of regulatory T cells) were scattered throughout the mucosa. Compared to healthy individuals, cats with FCGS had high circulating CD8+ effector memory cells with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L-). Gene expression in the affected tissues was enriched for genes associated with T-cell signaling, cell adhesion molecules, leukocyte migration, inflammatory signaling pathways, extracellular matrix-receptor interactions, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity, among others. These data are essential to understand disease pathogenesis, to inform mechanism of action studies for future and current therapies, and to help select prognostic biomarkers and potency assays for stem cell treatment of FCGS.

Since December 2019, an increasing number of cases of the 2019 novel coronavirus disease (COVID-19) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified in Wuhan, Hubei Province, China. Now, more cases have been reported in 200 other countries and regions. The pandemic disease not only affects physical health who suffered it, but also affects the mental health of the general population. This study aims to know about the impact of the COVID-19 epidemic on the health-related quality of life (HRQOL) of living using EQ-5D in general population in China.

Continuous femoral nerve block (cFNB) is effective for analgesia after total knee arthroplasty (TKA). However, it is not clear which low-dose regimen of ropivacaine infusion for cFNB provides adequate analgesia and enables rapid recovery. The aim of this study was to compare the effects of different cFNB regimens on rehabilitation of patients after TKA.