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Transforming growth factor-β1 (TGF-β1) protects against neuroinflammatory events underlying neuropathic pain. TGF-β signaling enhancement is a phenotypic characteristic of mice lacking the TGF-β pseudoreceptor BAMBI (BMP and activin membrane-bound inhibitor), which leads to an increased synaptic release of opioid peptides and to a naloxone-reversible hypoalgesic/antiallodynic phenotype. Herein, we investigated the following: (1) the effects of BAMBI deficiency on opioid receptor expression, functional efficacy, and analgesic responses to endogenous and exogenous opioids; and (2) the involvement of the opioid system in the antiallodynic effect of TGF-β1. BAMBI-KO mice were subjected to neuropathic pain by sciatic nerve crash injury (SNI). Gene (PCR) and protein (Western blot) expressions of μ- and δ-opioid receptors were determined in the spinal cord. The inhibitory effects of agonists on the adenylyl cyclase pathway were investigated. Two weeks after SNI, wild-type mice developed mechanical allodynia and the functionality of μ-opioid receptors was reduced. By this time, BAMBI-KO mice were protected against allodynia and exhibited increased expression and function of opioid receptors. Four weeks after SNI, when mice of both genotypes had developed neuropathic pain, the analgesic responses induced by morphine and RB101 (an inhibitor of enkephalin-degrading enzymes, which increases the synaptic levels of enkephalins) were enhanced in BAMBI-KO mice. Similar results were obtained in the formalin-induced chemical-inflammatory pain model. Subcutaneous TGF-β1 infusion prevented pain development after SNI. The antiallodynic effect of TGF-β1 was naloxone-sensitive. In conclusion, modulation of the endogenous opioid system by TGF-β signaling improves the analgesic effectiveness of exogenous and endogenous opioids under pathological pain conditions.
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http://dx.doi.org/10.1523/JNEUROSCI.4405-13.2014 | DOI Listing |
J Clin Psychol Med Settings
December 2024
Department of Psychiatry, Center for Health Outcomes and Interdisciplinary Research, Massachusetts General Hospital, 1 Bowdoin Square, Suite 106, Boston, MA, 02114, USA.
Chronic orofacial pain (COFP; i.e., musculoskeletal, neurovascular, or neuropathic pain in the face, mouth, or jaw that lasts for at least 3 months) is prevalent and debilitating.
View Article and Find Full Text PDFMed Cannabis Cannabinoids
November 2024
Faculty of Nursing, Khon Kaen University, Khon Kaen, Thailand.
Introduction: Diabetic peripheral neuropathy (DPN) represents a prevalent neurological complication affecting millions of patients globally. This clinical investigation evaluated the therapeutic efficacy and safety profile of a novel transdermal medical cannabis formulation (THC:CBD:CBN) in treating painful DPN of the lower extremities.
Methods: This phase III, double-blind, placebo-controlled, randomized clinical trial was conducted at Don Chan Hospital, Thailand, enrolling 100 participants over a 12-week intervention period.
Front Vet Sci
December 2024
Department of Small Animal Clinical Sciences, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Chronic neuropathic pain is underdiagnosed in companion animals. This paper will review the definition of pain and how classification and grading of neuropathic pain can be applied from human to veterinary medicine to increase the recognition of and the confidence in a neuropathic pain diagnosis. The mechanisms of nociception and the pathophysiology of the sensory systems that underlie the transition to chronic pain are described.
View Article and Find Full Text PDFNeurobiol Pain
November 2024
Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
PIKfyve (1-phosphatidylinositol 3-phosphate 5-kinase), a lipid kinase, plays an important role in generating phosphatidylinositol (3,5)-bisphosphate (PI(3,5)P). SGC-PIKFYVE-1, a potent and selective inhibitor of PIKfyve, has been used as a chemical probe to explore pathways dependent on PIKfyve activity. Based on reported changes in membrane dynamics and ion transport in response to PIKfyve inhibition, we hypothesized that pharmacological inhibition of PIKfyve could modulate pain.
View Article and Find Full Text PDFeNeurologicalSci
March 2025
Department of Internal Medicine, Miwa Naika Clinic, Toyama, Japan.
Background: Myalgic encephalomyelitis (ME) is associated with long COVID and also untoward sequelae after anti-coronavirus vaccination. Recently, oral minocycline therapy has been reported to ameliorate symptoms in patients with ME, particularly at the initial stage of the disease.
Methods: Oral minocycline (100 mg × 2 on the first day, followed by 100 mg/day for 41 days) was administered to 55 patients with ME that emerged during the "Corona era," including 19 patients with long COVID and 5 patients diagnosed with untoward sequalae following coronavirus vaccination.
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