Effects of Pregabalin Ultrasound Therapy and Nerve Exercises on Pain and Sensation in Diabetic Nerve Damage

Effects of Pregabalin Phonophoresis Combined With Nerve Flossing on Neuropathic Pain and Sensory Function in Peripheral Diabetic Neuropathy

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Neuropathic Pain; Painful Diabetic Peripheral Neuropathy; Peripheral Diabetic Neuropathy
• Intervention / Treatment: Drug: Pregabalin Phonophoresis; Device: Therapeutic Ultrasound; Procedure: Sural Nerve Flossing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Punjab Province
    • Faisalabad, Punjab Province, Pakistan, 3800
      • Syeda Khatoon e Jannat Trust Hospital & Special Education Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Participants receive pregabalin phonophoresis using 8% w/w pregabalin gel as the coupling medium. Therapeutic ultrasound is applied in pulsed mode at 1 MHz frequency and 1.0 W/cm² intensity for 15 minutes, followed by sural nerve flossing exercises. Treatment is administered five sessions per week for 12 weeks.	Drug: Pregabalin Phonophoresis; Pregabalin 8% w/w gel is administered through phonophoresis using pulsed therapeutic ultrasound to enhance transdermal drug delivery in patients with painful diabetic peripheral neuropathy.; Device: Therapeutic Ultrasound; Therapeutic ultrasound is applied for 15 minutes per session at 1 MHz frequency and 1.0 W/cm² intensity. Pulsed mode is used with pregabalin gel in the experimental group, while continuous mode with aquasonic gel is used in the control group.; Procedure: Sural Nerve Flossing; Sural nerve flossing exercises are performed immediately after ultrasound treatment using three sets of ten repetitions with a five-second hold and one-minute rest between sets.
Active Comparator: Control Group; Participants receive therapeutic ultrasound using aquasonic gel as the coupling medium. Ultrasound is applied in continuous mode at 1 MHz frequency and 1.0 W/cm² intensity for 15 minutes, followed by sural nerve flossing exercises. Treatment is administered five sessions per week for 12 weeks.	Device: Therapeutic Ultrasound; Therapeutic ultrasound is applied for 15 minutes per session at 1 MHz frequency and 1.0 W/cm² intensity. Pulsed mode is used with pregabalin gel in the experimental group, while continuous mode with aquasonic gel is used in the control group.; Procedure: Sural Nerve Flossing; Sural nerve flossing exercises are performed immediately after ultrasound treatment using three sets of ten repetitions with a five-second hold and one-minute rest between sets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	Pain intensity was measured using the Visual Analogue Scale (VAS), a 100-mm horizontal line anchored with "no pain" and "worst imaginable pain." Participants marked their perceived pain intensity, and scores were recorded in millimetres (0-100 mm), where higher scores indicate greater pain intensity.	Baseline, 6 weeks and 12 weeks (60 treatment sessions)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropathic pain assessment	Neuropathic pain was assessed using the Douleur Neuropathique en 4 Questions (DN4) questionnaire. It consists of 10 items evaluating pain characteristics and clinical examination findings. Each item was scored 0 or 1, with a total score ranging from 0 to 10. A score of ≥4 indicated probable neuropathic pain.	Baseline, 6 weeks and 12 weeks
Neuropathic pain and sensory function	Sensory function and neuropathic pain characteristics were assessed using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale. The scale included 7 items (5 symptom-based and 2 clinical tests). Scores range from 0 to 24, with a score ≥12 indicating neuropathic pain.	Baseline, 6 weeks and 12 weeks

Collaborators and Investigators

• Sponsor: Syeda Khatoon e Jannat Welfare Foundation
• Investigators: Study Chair: Dr Anbreena Rasool, DPT, MSPT, SKJ Special Education Centre, Faisalabad, Pakistan; Principal Investigator: Dr Mariam Razzaq, SKJ Special Education Centre, Faisalabad, Pakistan

Publications and helpful links

General Publications

• Raj RRM, Saravanan T, Preethi P et al. (2022) Comparative evaluation of therapeutic ultrasound and phonophoresis in myofascial pain dysfunction syndrome. Journal of Indian Academy of Oral Medicine and Radiology 34(3): 242-245.
• Mahanta SK, Warikoo D, Rawat N et al. (2024) Effect of nerve flossing on nerve conduction velocity and pain in patients with diabetic neuropathy: An experimental study. Diabetes 19: 22.
• Bragg S, Marrison ST, Haley S. Diabetic Peripheral Neuropathy: Prevention and Treatment. Am Fam Physician. 2024 Mar;109(3):226-232.
• Ardeleanu V, Toma A, Pafili K, Papanas N, Motofei I, Diaconu CC, Rizzo M, Stoian AP. Current Pharmacological Treatment of Painful Diabetic Neuropathy: A Narrative Review. Medicina (Kaunas). 2020 Jan 9;56(1):25. doi: 10.3390/medicina56010025.
• Akhtar S, Hassan F, Saqlain SR, Ali A, Hussain S. The prevalence of peripheral neuropathy among the patients with diabetes in Pakistan: a systematic review and meta-analysis. Sci Rep. 2023 Jul 20;13(1):11744. doi: 10.1038/s41598-023-39037-1.
• Alsharidah AS (2024) Efficacy of gabapentin phonophoresis on post mastectomy intercostobrachial neuralgia. Fizjoterapia Polska 24(3): 1-9.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2026
• Primary Completion (Actual): April 30, 2026
• Study Completion (Actual): May 31, 2026

Study Registration Dates

• First Submitted: June 27, 2026
• First Submitted That Met QC Criteria: June 27, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Neuropathic Pain; Sensory Function; Peripheral Diabetic Neuropathy; Pregabalin Phonophoresis; Sural Nerve Flossing
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neuralgia; Therapeutics; Diathermy; Hyperthermia, Induced; Ultrasonic Therapy
• Other Study ID Numbers: IRB-2026-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No