The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects.

PURPOSE OF REVIEW: This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives. RECENT FINDINGS: The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.

Importance of the formulation in the skin delivery of topical diclofenac: not all topical diclofenac formulations are the same.

Purpose: The current study aimed to compare 2 topical diclofenac products (diclofenac diethylamine [DEA] 1.16% emulsion and diclofenac sodium [Na] 5% gel). The quantitative evaluation of skin permeability and the qualitative evaluation of their physical characteristics were performed. Methods: The skin permeability of diclofenac DEA 1.16% emulsion and diclofenac Na 5% gel was compared in vitro using Franz diffusion cells following a single, fixed, 10 mg/cm2 dose of product applied to a 0.64 cm2 area of the stratum corneum surface of ex vivo human skin samples. The physical characteristics of the 2 formulations were assessed by rheological measurement and microscopy observation. Results: Diclofenac DEA 1.16% emulsion exhibited a statistically significant higher permeation through human skin at 24 hrs than diclofenac Na 5% gel (554 vs 361 ng/cm2, respectively; ratio of adjusted geometric means, 1.54 [95% CI, 1.14-2.07]). When expressed as a percentage of the applied dose of diclofenac that permeated through human skin, a 7-fold difference was observed between the diclofenac DEA 1.16% emulsion (0.54%) and the diclofenac Na 5% gel (0.077%). Qualitative composition and physical characterization showed differences between the formulations that may explain some of the permeation data observed. Based on rheological assessments, diclofenac Na 5% gel had a higher viscosity (24.82 Pa.s) than diclofenac DEA 1.16% emulsion (10.29 Pa.s). Conclusion: A topical diclofenac product with a higher concentration of the active ingredient does not necessarily lead to greater absorption relative to a product with lower concentration of the active ingredient but different characteristics. These observations highlight the importance of considering parameters beyond drug concentration, such as composition, which may influence the solubility of the drug and permeation of topical nonsteroidal anti-inflammatory drugs.