The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain.

Knee osteoarthritis is characterized by progressive damage and remodeling of all tissues in the knee joint. Pain is the main symptom associated with knee osteoarthritis. Recent clinical and pre-clinical studies have provided novel insights into the mechanisms that drive the pain associated with joint destruction. In this narrative review, we describe current knowledge regarding the changes in the peripheral and central nervous systems that occur during the progression of osteoarthritis and discuss how therapeutic interventions may provide pain relief.

Pulse Dose Methylprednisolone Therapy for Adult Idiopathic Inflammatory Myopathy.

Idiopathic inflammatory myopathies (IIM) are a rare group of autoimmune diseases characterized by muscle inflammation. Typically high-dose daily oral corticosteroids are used as the first-line therapy of IIM. Pulse dose intravenous methylprednisolone (IVMP) has been used for serious or refractory cases. Here, we systematically analyze the therapeutic effect of pulse dose IVMP in patients with IIM in a large municipal safety net medical center and review the literature on pulse IVMP in adult IIM. We conducted a retrospective chart review of patients who were diagnosed with IIM in the rheumatology clinics of the Cook County Health and Hospital Systems. Data collected included patient demographics, diagnosis, immunosuppressive therapies, serial serum creatine kinase (CK) measurements, and serial muscle strength testing. Seven patients received pulse dose IVMP for active myositis. At the time of pulse dose IVMP, the mean strength in the weakest muscle group was rated as 3.1 of 5 (range, 2-4; SD, 0.9) and the mean peak CK was 5746 U/L (range, 1602-14,039; SD, 4911). Dysphagia was reported in 5 of the 7 patients at the time of IVMP. Four to six weeks after IVMP, the mean strength in the weakest muscle group was 3.3 of 5 (range, 1-5; SD, 1.5) and mean peak CK was 1064 U/L (range, 63-1788, SD, 712). Four to six weeks after IVMP, dysphagia had resolved in 2 and improved in 3. At the end of follow-up, mean strength in the weakest muscle group was 4.7 of 5 (range, 4-5; SD, 0.5), mean peak CK was 480 U/L (range, 37-1016; SD, 337), and the mean prednisone dosage was 15 mg (range, 2.5-60; SD, 21). Although our study has certain limitations, our cohort of adult patients with IIM had marked improvement in clinical and biochemical outcomes. Four to six weeks after IVMP infusion, there was a rapid improvement in muscle enzyme levels, muscle strength, and dysphagia. This therapy warrants further controlled trials.

Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians.

OBJECTIVE: Inter-individual variations to methotrexate (MTX) response among rheumatoid arthritis (RA) patients have been attributed to clinical heterogeneity and genetic variations influencing MTX pharmacology. In this study, we analyzed the association of polymorphisms in ATIC, AMPD1, ADA, and ADORA2A from the purine biosynthetic pathway with MTX response in RA patients from north India. We also assessed the cumulative contribution of these polymorphisms together with those from the receptor-metabolizer-transporter and folate pathway genes that we have previously investigated. METHODS: RA patients recruited using the American College of Rheumatology criteria were grouped into good (n = 213) and poor (n = 68) responders to MTX, based on Disease Activity Score 28-3. Individual single nucleotide polymorphism association was tested using (chi)2 test, and cumulative contribution of all the single-nucleotide polymorphisms and cumulative contribution of all the SNPs and clinico-demographic factors were assessed using linear and logistic regression. RESULTS: G allele of ADA rs244076 [P = 0.02, odds ratio (95% confidence interval): OR (95% CI) = 1.66 (1.01-2.75)]; and T allele of ADORA2A rs5751876 [P = 0.04, OR (95% CI) = 1.55 (1.01-2.37)] were associated with poor response, but did not stand Bonferroni correction. On regression analyses, FPGS rs1544105, TYMS rs2853539, DHFR rs7387, and ADA rs244076 were identified as putative predictors for MTX response. Carriers of the FPGS rs1544105 AA and AG genotypes [OR (95% CI) = 3.47 (1.19-10.12)] and TYMS rs2853539 AA genotype [OR (95% CI) = 2.76 (1.50-5.07)] were predictors of poor response in our patient population. CONCLUSION: Genes from all the three pathways seem to contribute to MTX response in the Indian population. However, these observations need to be replicated in an independent sample set.