ABSTRACT
The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS); however, recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry-localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1/2 signaling and stimulation of PGE2 release, the classic pathway of MD-mediated renin release. Exogenous renin or prorenin added to the in vitro microperfused JGA-induced acute renin release, which was inhibited by removing the MD or by the administration of a PRR decoy peptide. To test the function of MD PRR in vivo, we established a new mouse model with inducible conditional knockout (cKO) of the PRR in MD cells based on neural nitric oxide synthase-driven Cre-lox recombination. Deletion of the MD PRR significantly reduced blood pressure and plasma renin. Challenging the RAS by low-salt diet + captopril treatment caused further significant reductions in blood pressure, renal renin, cyclooxygenase-2, and microsomal PGE synthase expression in cKO vs. wild-type mice. These results suggest that the MD PRR is essential in a novel JGA short-loop feedback mechanism, which is integrated within the classic MD mechanism to control renin synthesis and release and to maintain blood pressure.
Subject(s)
Blood Pressure , Juxtaglomerular Apparatus/enzymology , Proton-Translocating ATPases/metabolism , Receptors, Cell Surface/metabolism , Renin-Angiotensin System , Renin/metabolism , Vacuolar Proton-Translocating ATPases/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Biosensing Techniques , Blood Pressure/drug effects , Captopril/pharmacology , Cyclooxygenase 2/metabolism , Diet, Sodium-Restricted , Dinoprostone/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , HEK293 Cells , Humans , Juxtaglomerular Apparatus/drug effects , Male , Mice, Inbred C57BL , Mice, Knockout , Prostaglandin-E Synthases/metabolism , Proton-Translocating ATPases/deficiency , Proton-Translocating ATPases/genetics , Rats, Sprague-Dawley , Receptors, Cell Surface/deficiency , Receptors, Cell Surface/genetics , Renin-Angiotensin System/drug effects , Secretory Pathway , Signal Transduction , Vacuolar Proton-Translocating ATPases/genetics , Prorenin ReceptorABSTRACT
Implanting neuromodulation devices requires that pain medicine physicians be well-versed in proper surgical technique and postoperative wound management. To be able to identify abnormal wound healing, a basic understanding of normal wound healing is required. When postoperative wounds deviate from expected healing, it is important that pain medicine physicians entertain a broad differential diagnosis, including nonsurgical dermatologic pathology.
Subject(s)
Carcinoma, Basal Cell , Skin Neoplasms , Humans , Cicatrix , Carcinoma, Basal Cell/surgery , Skin Neoplasms/surgery , Spinal Cord , PainABSTRACT
BACKGROUND: Upper lateral hip pain is a common complaint in adults and is referred to as greater trochanteric pain syndrome (GTPS) and is more prevalent among older women. This is a debilitating condition that could result in lower physical activity and quality of life, and higher unemployment rate. GTPS is a clinical diagnosis, and many cases improve with conservative medical management (CMM). However, there is still a gap between patients not responding to CMM and those who are not good surgical candidates. Thus, percutaneous ultrasound tenotomy (PUT) may be a valuable treatment option to limit this gap. OBJECTIVES: Demonstration of the one-year pain and functional outcomes, including sit to stand. SETTING: Academic tertiary care medical center. METHODS: Forty-eight consecutive patients with refractory trochanteric pain due to iliotibial band (ITB) tendinopathy. Fifty-six hips were treated; 8 patients underwent bilateral procedures. Electronic medical record review of consecutive patients who underwent ITB TENEX® was performed at Montefiore Medical Center from December 2019 to December 2021. Institutional guidelines recommended TENEX® for greater trochanteric pain refractory to conservative treatment and ultrasound (US) confirmed ITB tendinopathy (hypoechogenicity or thickened tendon > 6 mm). Pain level, as well as sit-to-stand, side-lying, and walking tolerance levels were evaluated at baseline preprocedure visit and one-year visit. Follow-up was performed by independent practitioners and corroborated by chart review. RESULTS: Numeric Rating Scale (NRS-11) improved by 4 points across all patients. Seventy percent of patients endorsed pain relief at one-year visit. Median preprocedure NRS-11 was 9. The reported median NRS-11at one year was 5 (Wilcoxon signed rank NRS-11 demonstrated a Z score of -6.042 with P < 0.001). One-year analysis among all patients revealed 57%, 78%, and 66% improvement in side-lying, sit-to-stand, and walking tolerance levels, respectively. LIMITATIONS: We believe that our results must be confirmed with a randomized control trial with a control arm and more patients included. CONCLUSIONS: PUT of the ITB using the TENEX® tissue remodeling device could be a safe and effective treatment for ITB tendinopathy-associated GTPS.
Subject(s)
Bursitis , Musculoskeletal Diseases , Tendinopathy , Adult , Humans , Female , Aged , Tenotomy , Quality of Life , Guanfacine , Hip Joint/surgery , Pain , Bursitis/surgery , Tendinopathy/surgery , Ultrasonography, InterventionalABSTRACT
BACKGROUND: Chronic pain is a leading cause of disease burden and disability globally. The COVID-19 pandemic catalyzed a major paradigm shift in health care delivery with the universal adoption of telemedicine. Telehealth physical examination is particularly challenging and little guidance is available on this topic. OBJECTIVES: We attempt to describe the Point To the Area of Pain (PTAP) test and establish a consensus regarding its utility for musculoskeletal examination (MSK) via telehealth. STUDY DESIGN: The authors drafted an online survey. SETTING: The survey was sent to physicians and nurse practitioners within the authors' respective departments and institutions who routinely use telemedicine to treat pain METHODS: Respondents (n = 61) were asked about their primary specialty, comfort level in evaluating patients in pain, use of the PTAP test and its perceived clinical relevance to patient management, and other relevant questions. RESULTS: Respondents were predominantly trained in Physiatry (47.5%), Anesthesiology (23%), Neurology (13.1%) and Family Medicine (11.5%); 67.2% of providers treat pain related diseases > 75% of the time; 50.8% of respondents were "somewhat comfortable" at performing a virtual MSK exam and 29.5% were "not comfortable"; 65.5% utilize the PTAP test and 88.5% agree or strongly agree that this test provides extrinsic clinically relevant information. LIMITATIONS: The relatively small number of respondents. CONCLUSION: PTAP tests should not replace the standard accepted in-person or virtual physical examination in practice, but in the absence of a hands-on exam, the PTAP test is a clear and concise test that can easily be performed in conjunction with other techniques via telehealth, and in the context of assessing pain provides useful clinical information that can help guide medical decision making.