Rejected

Amidst a national crisis of opioid overdose, substantial uncertainty remains over how to safely and effectively address chronic pain. In response to this crisis, safety-net primary care clinics are instituting integrative group medical visits (IGMVs) for chronic pain management. Through two qualitative studies of IGMVs, we found that these groups acted as workarounds implemented by clinicians seeking to innovate upon standard pain management protocols. While clinical uncertainty is often framed as a problem to be managed, in this instance, overlapping uncertainties provided an opportunity through which enterprising clinicians could generate reform at the local level. However, these clinician-led changes were incremental, situational, and partial, and occurred outside of broader systemic reform. In the following article, we draw on 46 interviews with clinicians and staff associated with IGMVs and observations of 34 sessions of 22 distinct IGMVs. We begin by describing the structure of the IGMVs we observed. We analyze the multiple uncertainties surrounding chronic pain and its treatment at the time of our data collection, just before the opioid crisis was declared a national public health emergency. We then demonstrate how clinicians tinkered with existing pain management protocols via their involvement with IGMVs. Lastly, we discuss the conditions of possibility that allowed for the existence of IGMVs at our study sites, as well as the conditions of limitation that restricted the expansion of these groups. Our research points to the potential of IGMVs for treating chronic pain, while showing that IGMVs continue as an innovation by individual clinicians, not as a result of broader reforms.

Calcitonin Gene-Related Peptide (CGRP) has gradually emerged as a suitable therapeutic target to treat migraine. Considering the social and economic burden of migraine, it is fundamental to optimize the disease management with efficacious and safe treatments. In this scenario, drugs targeting GCRP, monoclonal antibodies (MoAbs) and gepants, represent new therapeutic strategies.

Nav1.7 is closely associated with neuropathic pain. Hydrogen sulfide (H2S) has recently been reported to be involved in numerous biological functions, and it has been shown that H2S can enhance the sodium current density, and inhibiting the endogenous production of H2S mediated by cystathionine β‑synthetase (CBS) using O‑(carboxymethyl)hydroxylamine hemihydrochloride (AOAA) can significantly reduce the expression of Nav1.7 and thus the sodium current density in rat dorsal root ganglion (DRG) neurons. In the present study, it was shown that the fluorescence intensity of H2S was increased in a spared nerve injury (SNI) model and AOAA inhibited this increase. Nav1.7 is expressed in DRG neurons, and the expression of CBS and Nav1.7 were increased in DRG neurons 7, 14 and 21 days post‑operation. AOAA inhibited the increase in the expression of CBS, phosphorylated (p)‑MEK1/2, p‑ERK1/2 and Nav1.7 induced by SNI, and U0126 (a MEK blocker) was able to inhibit the increase in p‑MEK1/2, p‑ERK1/2 and Nav1.7 expression. However, PF‑04856264 did not inhibit the increase in CBS, p‑MEK1/2, p‑ERK1/2 or Nav1.7 expression induced by SNI surgery. The current density of Nav1.7 was significantly increased in the SNI model and administration of AOAA and U0126 both significantly decreased the density. In addition, AOAA, U0126 and PF‑04856264 inhibited the decrease in rheobase, and the increase in action potential induced by SNI in DRG neurons. There was no significant difference in thermal withdrawal latency among each group. However, the time the animals spent with their paw lifted increased significantly following SNI, and the time the animals spent with their paw lifted decreased significantly following the administration of AOAA, U0126 and PF‑04856264. In conclusion, these data show that Nav1.7 expression in DRG neurons is upregulated by CBS‑derived endogenous H2S in an SNI model, contributing to the maintenance of neuropathic pain.

Neuropathic pain associated with cancers was caused by tumor itself or tumor therapy, which was aggravated by sensitizing nociceptor sensory neurons. The tumor microenvironment contributed to tumorigenesis, tumor progress, tumor metastasis, tumor immune resistance, tumor chemotherapy, and tumor immunotherapy. In the current study, we explored the contributions of the infiltrated dendritic cells insulted by Wnt1 in tumor microenvironment to neuropathic pain associated with cancers. The different transcriptome of infiltrated dendritic cells from lung adenocarcinoma and from juxtatumor indicated that thousands of genes were up-regulated by tumor microenvironment, some of which were enriched in pain pathway. The paracrine factors such as TNF, WNT10A, PDGFA, and NRG1 were also elevated in tumor-infiltrating dendritic cells. The receptors of paracrine factors were highly expressed on dorsal root ganglia (DRG), and not altered in pain conditions. Single cell RNA-seq data unveiled that TNFSF1 was expressed in neurons, microglial cells, and endothelial cells. PDGFRA was only expressed in microglial cells. ERBB3 was only expressed in neurons. FZD1and 3 were extensively expressed in various cells. The components composed of signaling pathways associated with above paracrine factors participated in pain networks. The transcription factors activated by paracrine factor signaling regulated the expression of genes associated with pain. TNF, WNT10A, and PDGFA were extensively expressed in multiple cancers, but their expression in patients did not distribute normally. These data indicated that infiltrated dendritic cells in tumor microenvironment promoted neuropathic pain by sensitizing nociceptor sensory neurons via paracrine factors. Blockage of paracrine factor signaling might alleviate cancer pain.

Enhanced recovery programs (ERP) is aimed at reducing a patient's surgical stress response, specifically by reducing the duration of catheterization. In cases of colorectal surgery, there is pronounced heterogeneity in urinary catheterization, which is largely explained by fear of acute urinary retention (AUR).

Chronic sciatica is a common condition. According to Traditional Persian Medicine and recent studies, calorie reduction is thought to be helpful for this condition. The purpose of this work is to evaluate a short-term low-calorie diet (LCD) for ameliorating chronic sciatica in the context of pain relief and reduced disability for patients. In this randomized controlled trial, 96 candidates for the nonsurgical treatment of chronic sciatica were randomly assigned to two groups to receive a 1-month LCD (intervention) or ordinary diet (control), both in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). Afterward, patients were visited at baseline and on days 15, 30, and 60 after treatment. Pain and disability were evaluated using the short-form McGill pain questionnaire (SFMPQ) and the Roland-Morris disability questionnaire (RMDQ), respectively. Both mean RMDQ scores and SFMPQ scores decreased significantly in the LCD group compared to the control group. SFMPQ descriptor scale scores at baseline and on days 15, 30, and 60 in the LCD group were 7.71 ± 1.69, 6.63 ± 1.61, 5.54 ± 1.87, and 4.96 ± 2.02, respectively, and in the control group were 6.63 ± 1.44, 6.69 ± 1.32, 6.64 ± 1.98, and 6.62 ± 2.53, respectively ( = 0.001). RMDQ scores at baseline and on days 15, 30, and 60 in LCD group were 11.17 ± 3.90, 8.60 ± 1.97, 7.50 ± 2.71, and 6.77 ± 3.06, respectively, and in the control group, 10.00 ± 2.20, 9.98 ± 2.29, 9.94 ± 2.94, and 9.85 ± 3.32, respectively ( < 0.001). A short-term (1-month) LCD is effective in decreasing pain and disability in candidates for nonsurgical treatment of chronic sciatica.

The prognosis of post-traumatic headache is poorly understood.

We evaluated the clinical management and risk factors for Trichomonas vaginalis-positive adolescents in upstate South Carolina.

The anti-resorptive properties of bisphosphonates have been explored to manage several conditions that traditionally have required a surgical solution. In osteonecrosis, their use is predicated on the principle that bone collapse occurs during the revascularisation phase of the disease. If the associated resorptive activity were modulated, the resultant preserved joint architecture may improve clinical outcome and reduce the need for joint replacement. Pre-clinical and small-scale clinical studies have given non-conclusive support for this principle. Adequately powered clinical trials with relevant long-term endpoints are still required to firmly clarify the clinical efficacy of this treatment. Several clinical studies have shown that bisphosphonates can reduce periprosthetic bone loss and, in some situations, enhance implant fixation in the early period after joint replacement. This may be advantageous in settings where osseointegration is problematic. However, the ultimate goals of their use in joint replacement has been to reduce the incidence of late periprosthetic inflammatory osteolysis, the main cause of prosthesis failure. Population-based observational studies have associated bisphosphonate use with a lower incidence of revision surgery, supported by pre-clinical data. However, clinical trials have, to date, failed to demonstrate any efficacy for the human disease. The timing of bisphosphonate administration for secondary prevention after acute osteoporotic fracture has been subject to extensive investigation, with pre-clinical studies showing increased callus formation but decreased remodelling and no effect on the restoration of mechanical integrity of bone. Meta-analysis of clinical trial data indicates that early administration of bisphosphonate after acute fracture does not adversely affect fracture union, pain or functional outcomes. Finally, bisphosphonates have also been explored as a treatment for complex regional pain syndrome type-I. A recent meta-analysis has shown a beneficial effect on visual analogue scale pain scores, but an increase in mild adverse events.

Nitrous oxide (NO) is underutilized in ambulatory urology. Here, we review available data regarding application, efficacy, and side effect profile of NO in ambulatory urologic procedures. Data were available from 11 studies. NO has been described in the setting of transrectal ultrasound-guided prostate biopsies, flexible cystoscopy, ureteral stent placement, and extracorporeal shockwave lithotripsy in adult patients and catheterization in children. Studies showed significant improvements in peri-procedural pain and anxiety relative to alternative (or none) forms of analgesia. Adverse effects were rare and self-limited. More widespread use of NO may result in cost savings and better patient tolerance with outpatient procedures.