Peripheral diabetic neuropathy (PDN) is a common complication of diabetes mellitus characterized by neuropathic pain, sensory disturbances, and impaired quality of life. This study aims to determine the effects of pregabalin phonophoresis combined with sural nerve flossing on neuropathic pain and sensory function in individuals with peripheral diabetic neuropathy. Participants will be randomly allocated to intervention groups and treated according to the study protocol. Outcomes related to neuropathic pain intensity and sensory function will be assessed before and after the intervention period to evaluate the effectiveness of the combined treatment approach.

Painful diabetic peripheral neuropathy is a common and disabling complication of diabetes that often leads to neuropathic pain, impaired sensory function, sleep disturbances, and reduced quality of life. Oral pregabalin, a first-line treatment for neuropathic pain, is effective but may cause central nervous system side effects such as dizziness and drowsiness, which can limit its clinical use. Localised delivery of pregabalin through phonophoresis may enhance transdermal drug absorption, providing targeted pain relief while minimising systemic adverse effects.

This randomised controlled trial aims to evaluate the effects of pregabalin phonophoresis combined with sural nerve flossing on neuropathic pain and sensory function in patients with painful diabetic peripheral neuropathy. Twenty-four participants aged 40-75 years will be randomly assigned to either an intervention group receiving pregabalin phonophoresis combined with sural nerve flossing or a control group receiving therapeutic ultrasound combined with sural nerve flossing. Treatments will be administered five times per week for 12 weeks.

Pain intensity will be assessed using the Visual Analogue Scale (VAS) and the Douleur Neuropathique 4 (DN4) questionnaire, while sensory function will be evaluated using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale. Outcome measures will be recorded at baseline, 6 weeks, and 12 weeks. Ethical approval has been obtained before study initiation. The findings of this study may provide evidence for an effective, non-invasive rehabilitation approach for managing painful diabetic peripheral neuropathy.

Inclusion Criteria:

• Patients of either gender between 40 to 75 years with a diagnosis of chronic diabetic neuropathic pain that is restricted to the foot area only.

Patients experiencing everyday pain in their lower extremities (one or both legs).

Patients with a pain score of 4 or higher on the Visual Analogue Scale (VAS) from 0 to 10 at screening and enrollment (after a seven-day washout period).

Patients scoring 12 or higher on the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Scale.

Patients with grade 0 or grade I diabetic foot status without active ulceration or infection, ensuring safe application of ultrasound-based therapies.

Presence of protective sensation loss, temperature discrimination impairment, or early microvascular changes commonly associated with diabetic foot risk.

Patients having HbA1c concentration levels below 12.2 % on screening.

Exclusion Criteria:

• Patients who have any complications of diabetes, including nephropathy, retinopathy or need for dialysis.

Patients who have active diabetic foot ulcers, infection, gangrene, Charcot foot, deep callus fissure, or open wounds in which the use of ultrasound is contraindicated.

Patients with a primary complaint of severe foot deformities that can potentially affect nerve symptoms.

Orthopaedic or neurological foot patients who do not have diabetic neuropathy can exhibit symptoms of peripheral neuropathy.

Patients who have Vitamin B12 deficiency (<180 ng/L), uncontrolled hypothyroidism, or other metabolic diseases which in themselves result in neuropathy.

Patients who have severe oedema, skin dermatological conditions on the site of application (eczema, dermatitis, skin hypersensitivity), and have intolerance of ultrasound gel or topical formulations.

Patients with a history of alcohol abuse, pregnant and lactating women.

Individual participant data will not be shared due to institutional data protection policies and the sensitive nature of patient clinical information. Only aggregated and anonymised results will be reported in publications.

The outcome assessor was blinded to group allocation and was responsible for collecting and recording outcome measures at baseline, 6 weeks, and 12 weeks.