miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels

Abstract: Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs (miRNAs) are a class of noncoding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for miRNAs regulated in dorsal root ganglia (DRG) neurons in a mouse model of bone metastatic pain, we identified miR-34c-5p as a functionally important pronociceptive miRNA. Despite these functional insights and therapeutic potential for miR-34c-5p, its molecular mechanism of action in peripheral sensory neurons remains unknown. Here, we report the identification and validation of key target transcripts of miRNA-34c-5p. In-depth bioinformatics analyses revealed Cav2.3, P2rx6, Oprd1, and Oprm1 as high confidence putative targets for miRNA-34c-5p. Of these, canonical and reciprocal regulation of miR-34c-5p and Cav2.3 was observed in cultured sensory neurons as well as in DRG in vivo in mice with cancer pain. Coexpression of miR-34c-5p and Cav2.3 was observed in peptidergic and nonpeptidergic nociceptors, and luciferase reporter assays confirmed functional binding of miR-34c-5p to the 3′ UTR of Cav2.3 transcripts. Importantly, knocking down the expression of Cav2.3 specifically in DRG neurons led to hypersensitivity in mice. In summary, these results show that Cav2.3 is a novel mechanistic target for a key pronociceptive miRNA, miR-34c-5p, in the context of cancer pain and indicate an antinociceptive role for Cav2.3 in peripheral sensory neurons. T...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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This article represents the findings from the queries over the first three months ’ queries and brings further clarity to our initial findings.Methods This quality improvement (QI) project was reviewed and approved by the Orlando Health/UFHealth Cancer Center Joint Oncology Committee for 2018-19. We began recording results of all E-FORSCE queries occurring after the law ’s implementation of July 1, 2018 through September 30, 2018. We informed each patient that the PDMP query had become mandatory in Florida, and we discussed the results of each query with each patient. Each query examined the last 12 months of t...
Source: Pallimed: A Hospice and Palliative Medicine Blog - Category: Palliative Care Tags: kollas opioid pain quality improvement statte Source Type: blogs
Conditions:   Breast Cancer;   Breast Cancer Lymphedema;   Pain;   Pain, Postoperative;   Pain, Chronic;   Mastectomy; Lymphedema;   Breast Surgery Interventions:   Other: Single rehabilitative treatment;   Other: Group rehabilitative treatment Sponsor:   University of Roma La Sapienza Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
CONCLUSIONS: While controversies related to medical cannabis are expected to remain rampant, the validated vignettes may facilitate assessment of clinical practices, which is essential for a successful implementation of medical cannabis policies. These vignettes may additionally be used in medical training for appropriate patient selection for medical cannabis authorization. PMID: 31713356 [PubMed - indexed for MEDLINE]
Source: The Israel Medical Association Journal - Category: General Medicine Tags: Isr Med Assoc J Source Type: research
We introduce a regional technique that involves the intraoperative placement of bilateral paravertebral catheters under direct visualization. The patient had stage IV lung cancer and was on chronic oxycodone therapy. He presented with a T10 metastatic lesion, and underwent spinal decompression with T7–L1 fusion and T10 corpectomy. Before fascial closure, catheters were advanced into the T10 paravertebral space under direct visualization by the surgeon bilaterally. Postoperatively, his pain was well controlled, and narcotic requirements were decreased. Our case report demonstrates that for patients undergoing posterio...
Source: A&A Case Reports - Category: Anesthesiology Tags: Case Reports Source Type: research
Patients using opioids to treat chronic non-cancer pain often experience side effects that may affect health-related quality of life (HRQOL). These side effects include opioid-induced constipation (OIC), sedat...
Source: BMC Gastroenterology - Category: Gastroenterology Authors: Tags: Research article Source Type: research
The American population is getting older and sicker. More Americans are facing life-threatening illness when approaching end of life. Palliative care has grown to meet the complex needs of this population. And yet, according to a 2017 article in the journal Palliative Care, many people living with a chronic life-threatening illness either do not receive any palliative care, or receive services only in the last phase of their illness. The National Consensus Project Clinical Practice Guidelines for Quality Palliative Care also addressed this issue, stating that a goal of their recently updated guidelines is “to improve...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Caregiving End of life Pain Management Source Type: blogs
A 78-year-old man with type 2 diabetes, hypertension, chronic anemia and recent-onset nephrotic syndrome presented with a 1-day complain of abdominal pain on his left side. He did not report any other symptoms. In his medical history, he had a partial gastrectomy for cancer 3 years ago
Source: The American Journal of Medicine - Category: General Medicine Authors: Tags: Clinical Communication to the Editor Source Type: research
ConclusionsSome opioids provided a short ‐term substantial pain relief in highly selected patients in some neuropathic pain syndromes.
Source: European Journal of Pain - Category: Anesthesiology Authors: Tags: SYSTEMATIC REVIEW Source Type: research
ConclusionsL ‐TOT may alter the immune system in CNCP patients, but the level of evidence is still weak. More studies are needed to clarify the impact of L‐TOT on immune system function.
Source: European Journal of Pain - Category: Anesthesiology Authors: Tags: REVIEW ARTICLE Source Type: research
Purpose of review To investigate the JZE alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment. Recent findings JZE was found to be significantly extended in patients with endometriosis, leading to the conclusion that endometriosis is a primary disease of the uterus, much like adenomyosis. Statistical correlation was then demonstrated between the severity of endometriosis and the depth of the adenomyosis infiltrates, hence the thickening of the JZE. Stem cells, predominantly found in the JZE were also found in histological sections of leiomyoma, suggested to be the ori...
Source: Current Opinion in Obstetrics and Gynecology - Category: OBGYN Tags: WOMEN'S HEALTH: Edited by Joseph Aquilina Source Type: research
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