Clinical trial NCT04628013: Influence of Noxious Electrical Stimulation on Chronic Pain From Knee Osteoarthritis
Official title: Influence of Noxious Electrical Stimulation on Chronic Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: electrical stimulation
Lead sponsor: University of New England
Sponsor class: OTHER
First posted: 2020-11-13
Enrollment: 13
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The investigators propose a single arm/pre-post trial to examine the effects of NxES on resting pain (BPI, ICOAP), pain sensitivity (PPT, HTS, CPM), movement-related pain (5xSTS), and physical function (5xSTS, KOOS) for people with knee OA. The investigators plan to examine the potential time-course effects after a single intervention (immediate, 1-hr, 24-, and 72-hours) and due to repeated treatment (3x/week for 2-weeks) at the end of treatment (post 72-hours and 4-weeks).
Primary purpose: TREATMENT

Brief summary: Knee osteoarthritis (OA) is the most common lower extremity joint pain condition, and it is estimated that 15 million people in the US are living with symptomatic knee OA and that more than half (8 million) are under 65 years of age. To that end, the Centers for Disease Control and Prevention strongly recommends non-pharmacological treatments for chronic pain including physical therapy and weight loss; however, these interventions have significant barriers that can prevent their success. An intervention that targets pain specifically is transcutaneous electrical nerve stimulation (TENS), which is a low-cost intervention with evidence to support pain reduction. As used in the majority of research to date, the intervention called "TENS" refers to the application of electricity across the skin that produces a tingling sensation that is strong but comfortable. However, electricity is applied at a noxious level is thought to result in strong activation of the endogenous pain modulation system, thus producing longer-lasting pain inhibition. However, noxious electrical stimulation (NxES) has rarely been investigated as a treatment intervention. Recent studies, including our own, demonstrate that NxES produces immediate and potentially greater pain relief. Despite some promising research, the clinical use of NxES is sparse and more research is necessary to demonstrate its effects on resting pain, movement-related pain, physical function, and quality of life. The investigators hypothesize that the application of NxES will activate pain modulation mechanisms and change the pain modulation profile toward an anti-nociceptive state in adults with chronic knee osteoarthritis (OA) pain, and thereby decrease pain (at rest and with movement), improve physical function, and improve quality of life. The investigators expect individual differences; therefore, participants will be classified at baseline and their response to the intervention tracked using psychophysical tests and clinical response. The hypothesis will be tested through 2 Specific Aims.

Aim 1: The investigators will test the magnitude and duration of pain relief and functional improvement of a single treatment with NxES in adults with chronic knee OA pain.

Aim 2: The investigators will determine if repeated NxES treatments show greater pain relief and/or functional improvements and if so, whether the gains plateau after a certain number of treatments.

The knowledge gained by this study will be important to physical therapists and other health care practitioners who treat people with chronic knee osteoarthritic pain. If noxious electrical stimulation is found to be an effective strategy to decrease pain at rest and with movement, it may lead to improved patient care, improved function, and decreased chronic pain in people with knee osteoarthritis.

Detailed description: Up to forty-four participants (22 for Aim 1; 22 for Aim 2) with knee OA will be recruited using advertisements, the Legacy Scholars research registry maintained by UNE's Center of Excellence in Aging and Health, from participants with knee OA previously involved in the investigator's research who indicated their willingness to participate in other studies, and from a local orthopedic surgeon group practice. Potential participants will complete a per-participation survey online or by phone that will be used to determine eligibility based on inclusion/exclusion criteria.

For Aims 1 and 2, eligible individuals will be asked to defer any plan for knee joint injections until after the testing period. Participants will be asked to refrain from taking any pain medications for at least 4 hours prior to testing. After giving informed consent, individuals who have diabetes will undergo sensory testing to confirm that their sensory detection threshold is no lower than the mean (+ 2 standard deviations) of the detection threshold of healthy older adults which is 1.4 g of force applied by a size 4.17 monofilament. This threshold is based on data collected in our laboratory using the 4-2-1- method of steps. If the individual is unable to perceive 1.4 g stimulus s/he will not continue in the study.

Protocol for Aim 1- Data collected for Aim 1 will occur over 4 sessions. The purpose of this aim is to determine the magnitude and duration of the day-to-day effects on clinical pain relief and quantitative sensory tests related to pain after a single NxES treatment.

Session 1: In this session we will gain informed consent, then perform a sensory screen (if necessary), collect demographic data and baseline questionnaire data and familiarize participants with the quantitative sensory testing (QST) procedures and to briefly experience the NxES treatment.

Session 2: During this session, participants will experience a single treatment with NxES and we will assess changes in pain and function and QST measures before and after the treatment. For the NxES Intervention, a pair of 2x3 inch electrodes will be placed on the medial and lateral sides of the knee. Pulses of electrical current (400 µs biphasic square wave pulses delivered at 50-100 pulses/second; 10-seconds on: 10-seconds off) will be applied for 20 minutes. The amplitude of the current will be increased until the participant rates the pain 50/100 on numeric pain rating scale. Pain intensity and unpleasantness will be assessed every two-min. and amplitude will be increased to maintain the 5/10 pain intensity level during the treatment. QST will be performed immediately after the treatment and 1 hour later. One- to two-minute washout periods will be provided between QST test repetitions and a 20-minute washout period will be provided after the NxES treatment and the post-treatment test of conditioned pain modulation.

Sessions 3-4: These sessions will occur 24-hours and 72-hours after session 2 and pain and function along with QST will be performed.

Protocol for Aim 2- The purpose of this aim is to determine if there is a cumulative response to NxES treatment on clinical pain and quantitative sensory tests related to pain. Data collected for Aim 2 will begin at least 1-week after the testing for Aim 1 and take place over a 2-week treatment period. Follow-up testing will take place 72-hours and 4-weeks after the last NxES treatment session.

Session 1: This session will be used to re-collect baseline questionnaire data and re-familiarize participants with procedures if it has been greater than 2-weeks since participation in Aim 1 or if they declined participation in Aim 1.

Session 2: During this session, participants will receive the first NxES treatment and undergo assessment of QST, pain, and function.

Session 3-7: These sessions are NxES treatment sessions. Pain and QST assessment will be collected at the beginning of sessions 3,5 \& 7 only.

Session 8: No treatments will be performed; post-treatment assessments will occur at 72 hours after session 7.

Session 9: No treatments will be performed; post-treatment assessments will be completed 4 weeks after session 7.

Sessions 2-7 must be completed within 18 calendar days in order to preserve the fidelity of the intervention dosage.

Eligibility criteria: Inclusion Criteria:

* follow instructions given in English
* have chronic knee joint-related pain of at least 6-months duration with a pain rating of at least 30/100 mm (0 = no knee pain, 100 = worst imaginable knee pain) over the last 24-hrs.
* report knee pain of at least 30/100 mm with walking, during sit-to-stand transfers, or during stair use

Exclusion Criteria:

* prior experience with NxES
* knee joint injections in the last 3-months or during the time of study participation
* history of total knee arthroplasty in the involved knee
* history of other surgery during the previous 6-months
* history of fibromyalgia or other chronic pain condition
* history of rheumatoid arthritis or related condition
* history of neurologic disorders
* history of cardiovascular or pulmonary disorders that would prevent the completion of the sit-to-stand test
* physician-diagnosed Raynaud's Syndrome
* history of diabetes with diminished sensation
* history of dementia/cognitive impairment

Primary outcomes:
measure: Change in Pain Pressure Threshold (PPT medial tibial plateau)
timeFrame: Aim 1: Assessed at baseline, immediately post-treatment, 24- and 72-hours post-treatment. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
measure: Change in Brief Pain Inventory (BPI)
timeFrame: Aim 1: Assessed at baseline, immediately post-treatment, 24- and 72-hours post-treatment. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
measure: Change in Movement-Related Pain
timeFrame: Aim 1: Assessed at baseline, immediately post-treatment, 24- and 72-hours post-treatment. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
measure: Change in Intermittent and Constant Osteoarthritis Pain scale (ICOAP)
timeFrame: Aim 1: Assessed at baseline only. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
Secondary outcomes:
measure: Change in Conditioned Pain Modulation (CPM)
timeFrame: Aim 1: Assessed at baseline, immediately post-treatment, 24- and 72-hours post-treatment. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
measure: Change in Heat Temporal Summation (HTS)
timeFrame: Aim 1: Assessed at baseline, immediately post-treatment, 24- and 72-hours post-treatment. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
measure: Change in Pressure Pain Threshold (PPT wrist)
timeFrame: Aim 1: Assessed at baseline, immediately post-treatment, 24- and 72-hours post-treatment. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
measure: Change in Five-Times Sit-to-Stand (5xSTS) Test
timeFrame: Aim 1: Assessed at baseline, immediately post-treatment, 24- and 72-hours post-treatment. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
measure: Change in Knee injury and Osteoarthritis Outcome score (KOOS)
timeFrame: Aim 1: Assessed at baseline only. Aim 2: Assessed at baseline, at 72-hours after final intervention, and 4-weeks post-intervention.
Other outcomes:
measure: Pain Catastrophizing Scale (PCS)
timeFrame: Aim 1: Baseline only Aim 2: Baseline only
measure: Pain Sensitivity Questionnaire (PSQ)
timeFrame: Aim 1: Baseline only Aim 2: Baseline only
measure: Brief Resiliency Scale (BRS)
timeFrame: Aim 1: Baseline only Aim 2: Baseline only
measure: Depression Anxiety and Stress Scale (DASS-21)
timeFrame: Aim 1: Baseline only Aim 2: Baseline only
Locations:
city: Portland
country: United States
facility: University of New England
state: Maine
Study officials:
affiliation: University of New England
name: Scott K Stackhouse, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stackhouse SK, Taylor CM, Eckenrode BJ, Stuck E, Davey H. Effects of Noxious Electrical Stimulation and Eccentric Exercise on Pain Sensitivity in Asymptomatic Individuals. PM R. 2016 May;8(5):415-24. doi: 10.1016/j.pmrj.2015.07.009. Epub 2015 Aug 3.
citation: Eckenrode BJ, Stackhouse SK. IMPROVED PRESSURE PAIN THRESHOLDS AND FUNCTION FOLLOWING NOXIOUS ELECTRICAL STIMULATION ON A RUNNER WITH CHRONIC ACHILLES TENDINOPATHY: A CASE REPORT. Int J Sports Phys Ther. 2015 Jun;10(3):354-62.
citation: Eckenrode BJ, Kietrys DM, Stackhouse SK. PAIN SENSITIVITY IN CHRONIC ACHILLES TENDINOPATHY. Int J Sports Phys Ther. 2019 Dec;14(6):945-956.
citation: Defrin R, Ariel E, Peretz C. Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment. Pain. 2005 May;115(1-2):152-60. doi: 10.1016/j.pain.2005.02.018.