![]() ![]() ![]() The sonophoresis mechanism of ultrasound uses thermal, cavitational and streaming properties as well as continuous low-intensity ultrasound that can be used as a potential tool to enhance localized transdermal drug delivery to treat arthritis. Acoustic streaming increases drug delivery in phantom muscle and brain tissues. Continuous ultrasound also creates a convective phenomenon of acoustic streaming the bulk flow of fluids and molecules in the propagation path of the ultrasonic wave. The pressure changes due to acoustic waves, allow ultrasound to induce cavitation effects in the cell membrane, increasing cell permeability and the potential for drug delivery. Thermal effects lead to increased tissue plasticity and blood flow to enhance nutrient transport, vasodilation and removal of cellular waste products. ![]() Mechano-transduction leads to matrix regeneration and activation of multiple molecular and cellular pathways. ![]() Therapeutic ultrasound has mechano-transductive, thermal, and cavitation-based effects. The application of ultrasound varies with intensity and frequency of the ultrasound signal. Ultrasound has medical applications for therapeutic and diagnostics purposes. Ultrasound is a high-frequency (nonionizing radiation) mechanical wave with a frequency above 20 kHz (not audible to the human ear). Recent meta-analyses have shown that diclofenac is more effective, relative to other NSAIDs, such as ketoprofen, ibuprofen and piroxicam. Furthermore, inhibition of COX-1 and COX-2 downregulate pain sensitization through the L-arginine/nitric oxide/cyclic guanosine monophosphate pathway. It inhibits COX-1 and -2, the underlying expression of prostaglandin-2 and thromboxane synthesis approximately 3–1000× more than other NSAIDs. Diclofenac is one of the most common NSAIDs used. The topical application of NSAIDs reduces the systemic risks but has reduced efficacy due to limited penetration through the skin. The long-term application of orally administered NSAIDs has adverse effects on multiple organs, including the kidney, liver, heart and intestinal tract. NSAIDs are broadly used for pain management and have short-term efficacy. Ultimately most patients with moderate-to-severe arthritis progress onto surgical procedures to repair and/or replace the damaged joint. The pain is managed through weight loss, physical therapy, hot/cold therapy, ultrasound therapy, compression therapy and either systemic or topical nonsteroidal anti-inflammatory drugs (NSAIDs). Ĭurrently, there is no cure for arthritis and arthritis-induced pain. It is the disease of the whole joint, which involves activation of catabolic enzymes, nitric oxide synthase-2, cyclooxygenases-(COX)-2, degradation of the matrix through matrix metalloproteinases (MMP-1, MMP-3 and MMP-13), a disintegrin and metalloproteinase with thrombospondin-1 domains 4 and 5 and activation of cytokines, such as (IL-6, IL-1β and TNF-α), leading to the destruction of the total joint and chronic pain. There are multiple kinds of arthritis, with osteoarthritis and rheumatoid arthritis being the two primary forms. Per-person medical costs attributed to an average of $11,052 per year for arthritis patients. Arthritis is one of the most prevalent medical conditions affecting 54 million people in the USA and costs the US economy approximately $304 billion annually in medical expenses and lost wages. ![]()
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