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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University of Faisalabad
- Enrollment
- 35
- Locations
- 1
Study Overview
Brief Summary
Knee osteoarthritis (OA) is a common condition causing pain, stiffness, and difficulty walking. Many patients with advanced (Grade III) knee OA also experience neuropathic pain - burning, tingling, or electric shock sensations - which is harder to treat with standard physiotherapy. Oral pregabalin works for neuropathic pain but causes side effects like dizziness and drowsiness. This study tests whether delivering pregabalin through the skin using ultrasound (phonophoresis), combined with calf muscle stretching (Muscle Energy Technique), can reduce nerve pain and improve walking better than ultrasound alone.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosed Grade III knee osteoarthritis confirmed by Kellgren-Lawrence grading scale (radiograph within past 12 months or newly obtained).
- •Neuropathic pain component confirmed by DN-4 questionnaire (score ≥4).
- •Age between 40 and 70 years inclusive.
- •Both male and female participants.
- •Unilateral or bilateral knee involvement (if bilateral, the more symptomatic knee selected for assessment and treatment).
- •Willing and able to provide written informed consent.
- •Available to attend 4 sessions per week for 4 consecutive weeks (total 16 sessions).
- •Able to understand and follow verbal instructions (for MET).
Exclusion Criteria
- •Diabetic neuropathy (diagnosed or DN-4 score attributable to diabetes rather than knee OA).
- •Active skin lesions, wounds, infections, or dermatitis on the knee or calf.
- •Metal implants (including knee replacement), pacemaker, or other electronic implant (contraindications for ultrasound).
- •Received intra-articular knee injection (corticosteroid or hyaluronic acid) within the last 3 months.
- •Grade I, II, or IV knee osteoarthritis (Kellgren-Lawrence).
- •Aseptic arthritis of knee (rheumatoid, psoriatic, gouty).
- •Any lower extremity deformity (genu varum >15°, genu valgum >15°, fixed flexion deformity >15°).
- •Previous knee replacement surgery (partial or total).
- •Known allergy or hypersensitivity to pregabalin, gabapentin, or any gel components.
- •Pregnant or lactating women (ultrasound safety in pregnancy not established for non-obstetric use).
- •Concurrent participation in another interventional study.
- •Diagnosis of fibromyalgia, complex regional pain syndrome, or other centralized pain disorder that might confound neuropathic pain assessment.
- •Active malignancy or history of knee malignancy.
- •Deep vein thrombosis or thrombophlebitis in lower limb.
Investigators
Muhammad Muneeb Jafar
Assistant Professor, Department of Rehabilitation Sciences
University of Faisalabad