Evaluating the Combined Efficacy of Pregabalin-Encapsulated Hydrogel Phonophoresis Along With Gastrocnemius Muscle Energy Technique on Neuropathic Pain and Mobility in Grade III Knee Osteoarthritis

Knee osteoarthritis is the most prevalent degenerative joint disease globally, characterized by progressive loss of articular cartilage, subchondral bone remodeling, synovial inflammation, and capsular thickening. While traditionally considered a nociceptive pain condition, accumulating evidence demonstrates that a significant subset of patients - particularly those with advanced radiographic severity - exhibit neuropathic pain features. This neuropathic component arises from peripheral nerve sensitization, central sensitization, and structural changes in both peripheral and central nervous systems.

Grade III knee osteoarthritis (Kellgren-Lawrence classification) represents severe cartilage loss with joint space narrowing, osteophyte formation, and subchondral sclerosis. In this population, neuropathic pain prevalence is substantially elevated compared to earlier grades. Clinical descriptors include burning sensations, electric shock-like pains, tingling, and allodynia.

Pregabalin, a gabapentinoid anticonvulsant, exerts its analgesic effect by binding to the alpha-2-delta subunit of voltage-gated calcium channels, reducing calcium influx and subsequent release of excitatory neurotransmitters including glutamate, norepinephrine, and substance P. While effective for neuropathic pain, oral administration produces dose-dependent central nervous system side effects that frequently limit tolerability and compliance.

Phonophoresis represents a transdermal drug delivery method utilizing therapeutic ultrasound to enhance skin permeability and drive medication into underlying tissues. The proposed mechanism involves cavitation, acoustic streaming, thermal effects, and alterations in stratum corneum lipid bilayer structure. Previous studies have demonstrated successful phonophoretic delivery of gabapentin (a pregabalin analog) for post-mastectomy neuralgia, with superior analgesia compared to topical gel alone.

Concurrently, lower extremity muscle dysfunction is well-documented in knee osteoarthritis. The gastrocnemius muscle, spanning both knee and ankle joints, exhibits increased stiffness measured by shear wave elastography. This stiffness alters plantar pressure distribution, increases knee joint compressive forces during gait, and contributes to reduced walking speed, stair-climbing difficulty, and overall mobility limitation.