I am a
Home I AM A Search Login

Accepted

Share this

Angiotensin II receptor type 1 blocker candesartan improves morphine tolerance by reducing morphine‑induced inflammatory response and cellular activation of BV2 cells via the PPARγ/AMPK signaling pathway.

Morphine is the most common drug of choice in clinical pain management; however, morphine tolerance presents a significant clinical challenge. The pathogenesis of morphine tolerance is known to be closely associated with angiotensin II receptor type 1 (AT1R) in microglia. As an AT1R antagonist, candesartan may serve an important role in regulating morphine tolerance. Therefore, the present study aimed to investigate the role of candesartan in morphine tolerance, and to explore the underlying mechanism. To meet this aim, BV2 microglial cells were treated with morphine or candesartan alone, or as a combination, and the expression levels of AT1R in BV2 cells were detected by reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. The levels of the inflammatory cytokines tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 were subsequently detected by ELISA and western blotting. In addition, immunofluorescence analysis, western blotting and RT‑qPCR were used to detect the expression levels of the BV2 cell activation marker, ionized calcium‑binding adaptor molecule 1 (IBA‑1). Western blotting was also used to detect the expression levels of peroxisome proliferator‑activated receptor‑γ/AMP‑activated protein kinase (PPARγ/AMPK) signaling pathway‑associated proteins. Finally, the cells were treated with the PPARγ antagonist GW9662 and the AMPK inhibitor compound C to further explore the mechanism underlying the effects of candesartan on improving morphine tolerance. The expression levels of AT1R were revealed to be significantly increased following morphine induction; however, candesartan treatment inhibited the expression levels of AT1R, the levels of inflammatory cytokines and the protein expression levels of IBA‑1 in morphine‑induced BV2 cells in a dose‑dependent manner. These processes may be associated with activation of the PPARγ/AMPK signaling pathway. Taken together, the present study revealed that treatment with candesartan reduced morphine‑induced inflammatory response and cellular activation of BV2 cells via PPARγ/AMPK signaling.

Learn More >

The timing point of exercise intervention regulates neuropathic pain-related molecules in the ipsilateral dorsal root ganglion neurons after sciatic nerve injury.

The purpose of this study was to determine whether the timing of tread-mill exercise application can control expression levels of neuropathic pain- and regeneration-related proteins in the ipsilateral lumbar 4 (L4) to 6 (L6) dorsal root ganglion cells (DRG) after sciatic nerve injury (SNI). The experimental rats were randomly divided into five groups: the normal control, SNI+sedentary (IS), exercise+SNI (EI), SNI+exercise (IE), exercise+SNI+exercise (EIE) groups. The rats in exercise groups per-formed treadmill exercise at a speed of 8 m/min for 30 min once a day during 14 days before and/or after SNI. For investigating the expression of specific neuropathic pain and regeneration-related proteins in DRG, we prepared L4 to L6 DRG in the ipsilateral side. In the quantitative analysis, growth associated protein 43 (GAP-43) and brain-derived neurotrophic factor levels were further increased in the ipsilateral DRG at all treadmill exercise groups than those in IS group. In the histological findings, GAP-43 was qualitatively increased IE and EIE groups than IS group at DRG. Wnt3a and β-catenin were dramatically downregulated in EIE and IE groups than IS groups. In addition, nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-α were significantly decreased in IE and EIE groups than IS group in the ipsilateral DRG. Our findings suggested novel information that regular low-intensity exercise before and/or after SNI might be a therapeutic and preventive approaches for relieving neuropathic pain and improving axonal elongation after peripheral nerve injury.

Learn More >

Quality of life after trigeminal nerve block in refractory trigeminal neuralgia: A retrospective cohort study and literature review.

To evaluate the effect of trigeminal nerve block (TNB) on patients' quality of life (QOL) 15 days after the procedure in patients with refractory TN.

Learn More >

RNA interference-mediated silencing of DNA methyltransferase 1 attenuates neuropathic pain by accelerating microglia M2 polarization.

DNA methyltransferase 1 (DNMT1) exerts imperative functions in neuropathic pain (NP). This study explored the action of RNA interference-mediated DNMT1 silencing in NP by regulating microglial M2 polarization.

Learn More >

Variations in comorbidity burden in people with type 2 diabetes over disease duration: A population-based analysis of real world evidence.

The prevalence of type 2 diabetes (T2DM) is increasing, but increasing longevity among persons with diagnosed diabetes may be is associated with more extensive and diverse types of morbidity. The extent and breadth of morbidity and how this varies across sub-groups is unclear and could have important clinical and public health implications. We aimed to estimate comorbidity profiles in people with T2DM and variations across sub-groups and over time.

Learn More >

Pain management strategies in urethral reconstruction: a narrative review.

Few investigations explore pain recovery comprehensively following urethral reconstruction, and understanding pain pathways that lead to discomfort following reconstruction has posed challenges. Options for pain control aside from opioids continue to be in the early forms of investigation, and remain an important strategy to combat the well-documented burden of the opioid epidemic. We conduct a detailed assessment of pain pathways in patients undergoing urethral reconstruction and further outline non-narcotic based pain management strategies in those undergoing urethroplasty.

Learn More >

Polymyalgia Rheumatica and Giant Cell Arteritis: Rapid Evidence Review.

Polymyalgia rheumatica and giant cell arteritis are inflammatory conditions that occur predominantly in people 50 years and older, with peak incidence at 70 to 75 years of age. Polymyalgia rheumatica is more common and typically presents with constitutional symptoms, proximal muscle pain, and elevated inflammatory markers. Diagnosis of polymyalgia rheumatica is clinical, consisting of at least two weeks of proximal muscle pain, constitutional symptoms, and elevated erythrocyte sedimentation rate or C-reactive protein. Treatment of polymyalgia rheumatica includes moderate-dose glucocorticoids with a prolonged taper. Giant cell arteritis, also known as temporal arteritis, usually presents with new-onset headache, visual disturbances or changes, constitutional symptoms, scalp tenderness, and temporal artery symptoms. Inflammatory markers are markedly elevated. Temporal arterial biopsy should be used for diagnosis. However, color duplex ultrasonography, magnetic resonance imaging, and fluorodeoxyglucose positron emission tomography may be helpful when biopsy is negative or unavailable. All patients with suspected giant cell arteritis should receive empiric high-dose glucocorticoids because the condition may lead to blindness if untreated. Tocilizumab is approved by the U.S. Food and Drug Administration for giant cell arteritis and should be considered in addition to glucocorticoids for initial therapy. Polymyalgia rheumatica and giant cell arteritis respond quickly to appropriate dosing of glucocorticoids but typically require prolonged treatment and have high rates of relapse; therefore, monitoring for glucocorticoid-related adverse effects and symptoms of relapse is necessary. Methotrexate may be considered as an adjunct to glucocorticoids in patients with polymyalgia rheumatica or giant cell arteritis who are at high risk of relapse.

Learn More >

Silicone Barrier Cream in treatment of Atopic Dermatitis: A Literature Review.

Atopic dermatitis is a complex skin disorder that requires multidisciplinary treatment modalities to best improve the results of the condition. Although silicone formulations have been used for the treatments of wounds, ulcers, and burns, we aim to highlight the use of a silicone solution for the treatment of eczema. Components of the silicone formula may enhance treatment for AD, such as in the wet wrap therapy, and can be a useful addition. In this report, we aim to discuss the use and properties of the wet wrap therapy with silicone and the potential benefits of applying this formula for the treatment of AD in the future.

Learn More >

The effect of a quality improvement project on post-operative opioid use following outpatient spinal surgery.

Prescribing opioids upon discharge after surgery is common practice; however, there are many inherent risks including dependency, diversion, and medical complications. Our prospective pre- and post-intervention study investigates the effect of a standardized analgesic prescription on the quantity of opioids prescribed and patients' level of pain and satisfaction with pain control in the early post-operative period.

Learn More >

Endometriosis: Evaluation and Treatment.

Endometriosis is an inflammatory condition caused by the presence of endometrial tissue in extra-uterine locations and can involve bowel, bladder, and all peritoneal structures. It is one of the most common gynecologic disorders, affecting up to 10% of people of reproductive age. Presentation of endometriosis can vary widely, from infertility in asymptomatic people to debilitating pelvic pain, dysmenorrhea, and period-related gastrointestinal or urinary symptoms. Diagnosis of endometriosis in the primary care setting is clinical and often challenging, frequently resulting in delayed diagnosis and treatment. Although transvaginal ultrasonography is used to evaluate endometriosis of deep pelvic sites to rule out other causes of pelvic pain, magnetic resonance imaging is preferred if deep infiltrating endometriosis is suspected. Laparoscopy with biopsy remains the definitive method for diagnosis, although several gynecologic organizations recommend empiric therapy without immediate surgical diagnosis. Combined hormonal contraceptives with or without nonsteroidal anti-inflammatory drugs are first-line options in managing symptoms and have a tolerable adverse effect profile. Second-line treatments include gonadotropin-releasing hormone (GnRH) receptor agonists with add-back therapy, GnRH receptor antagonists, and danazol. Aromatase inhibitors are reserved for severe disease. All of these treatments are effective but may cause additional adverse effects. Referral to gynecology for surgical management is indicated if empiric therapy is ineffective, immediate diagnosis and treatment are necessary, or patients desire pregnancy. Alternative treatments have limited benefit in alleviating pain symptoms but may warrant further investigation.

Learn More >

Search