Uncovering the Mechanism of Pain Relief by Peripheral Transcutaneous Magnetic Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Pressure Pain Assessment
研究概览
简要总结
This research aims to uncover the Mechanisms of pain relief through the FDA-cleared peripheral transcutaneous magnetic stimulation (pTMS) device by MagVenture. 50 people with chronic pain (post-surgical or post-traumatic) will be identified and recruited. The eligibility for participation in the study will be evaluated by a series of pain and mental health questionnaires followed by quantitative sensory testing (QST) to assess response to noxious heat, cold, and pressure stimuli. Blood will be drawn to isolate plasma, serum, and leukocytes. Participants will then undergo pTMS at the site of pain for four consecutive days. At the end of the therapy, pain testing will be done again, followed by blood withdrawal to assess the changes in plasma and leukocyte levels of mediators of pain. It is anticipated that pTMS will increase mediators of pain relief and reduce inflammatory mediators. Risks: It is possible that a few participants may not respond to pTMS therapy. However, plasma analysis of mediators of pain may help stratify these participants into responders vs. non-responders. Risks associated with the study are minimal and mainly involve discomfort associated with pain testing. The importance of knowledge gained includes understanding pain relief mechanisms by medical devices such as pTMS, which will result in better pain management.
详细描述
Chronic pain (pain lasting ≥3 months) is a debilitating condition associated with depression, dementia, increased risk of suicide, decreased productivity, and substance abuse. Opioids continue to be a crucial part of pain management. However, the misuse of prescription opioids has led to a shift towards injectable opioids such as heroin, with nearly 80% of new heroin users reporting prior use of prescription opioids. Further, co-morbid substance abuse can exacerbate pain symptoms despite pharmaceutical treatment, revealing the limitations of current pain management strategies. Due to tolerance, people with a history of opioid dependence often need higher doses of opioids to treat acute pain and long-term opioid use paradoxically worsens chronic pain. From a public health perspective, there is an increased chance of transmitting and acquiring hepatitis B and C due to opioid use-related engagement in risky behaviors. Moreover, the economic burden of untreated pain in the US is estimated to be more than $100 billion per year. Therefore, there is an urgent need to develop novel therapeutic strategies and reduce reliance on opioids.
Peripheral Transcutaneous Magnetic Stimulation (pTMS) is a non-invasive method of relieving pain by stimulating the target area with magnetic pulses. The magnetic field pulse passing into the body induces a voltage difference between any two points, which creates an electric field and causes electrons to flow between these two points. The magnetic field can penetrate deep tissue, such as spinal nerve roots or muscles. No mechanical contact is necessary, making pTMS applicable to patients with extreme hypersensitivity or allodynia to skin touch. pTMS is FDA-cleared for post-traumatic and post-surgical chronic pain. However, to date, no clear evidence has emerged about pTMS's potential mechanism of pain relief, which has moderated its applicability and acceptability.
The study will require recruiting patients over the phone, followed by an on-site visit, which includes patient interaction, blood collection, pain study, performing pTMS therapy at the site of pain, and patient monitoring. Three more on-site visits on consecutive days will include pTMS therapy. The last (fourth) visit will include specimen collection and a pain study. The first and the fourth visits will take 2.5 hours, while the second and the third visits will require 30 minutes. The participants will be followed over the phone every 30 days till the completion of the study to inquire about their wellness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of chronic peripheral pain secondary to trauma or surgery. Age 19 - 80; the lower end of this age range was chosen to capture young adults with pain, and participants over 80 years are increasingly likely to meet one or more
排除标准
- •Currently receiving pain medication Chronic pain must self-report peripheral pain, more than once per week, for at least three consecutive months
- •Exclusion Criteria:
- •Implanted Electronic Devices and / or Conductive Objects in or near the head: Patients who have an implanted device that is activated or controlled in any way by physiological signals (examples: deep brain stimulators, cochlear implants, and vagus nerve stimulators).
- •Non-Removable Metallic Objects near the coil: Patients who have conductive, ferromagnetic, or other magnetic-sensitive metals implanted in their head or within 30 cm of the treatment coil (examples: cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, and bullet fragments). F NOTE: Standard amalgam dental fillings are not affected by the magnetic field and are acceptable in patients.
- •Active microbial infections may alter the quantity or quality of blood inflammatory cells such as monocytes and neutrophils.
- •Positive Urine Drug test: (COC/AMP/OPI/mAMP/PCP/BAR/BZO/MTD/MDMA/OXY/PPX/BUP/TCA) Use of any medication other than pain medications. However, participants will not be excluded or asked to withdraw from medications used for pain management since temporary withdrawal from these medications could affect pain measures (exceptions will be therapies such as methadone or buprenorphine used to treat opioid addiction). Only those who have been stable on these medications for at least 60 days will be included. All patient medications used for at least 60 days prior to participation will be recorded and controlled in statistical analyses as needed.
- •Systemic rheumatic disease (e.g., rheumatoid arthritis, systemic lupus erythematosus). These rheumatologic conditions will be excluded due to their autoimmune characteristic.
- •Cachexia (wasting syndrome) and severe frailty as determined by the Groningen Frailty Index (score >4). This exclusion is in place to protect against the stress of experimental pain testing.
- •Uncontrolled hypertension (i.e. SBP/DBP of >140/90) or cardiovascular or peripheral arterial disease. These exclusions are in place primarily for safety reasons because the cold pressor task represents a cardiovascular challenge. However, uncontrolled hypertension can also affect pain perception, which is another reason for excluding these individuals.
- •Poorly controlled diabetes (HbA1c > 8%) for both safety reasons and because diabetic neuropathy could alter pain perception.
- •Neurological disease (e.g. Parkinson's, multiple sclerosis). Serious psychiatric disorder requiring hospitalization within the past 12 months or characterized by active suicidal ideation. Any participant deemed to be actively suicidal upon study screening will be escorted to the emergency room and evaluated by the Psychiatry Service.
- •A diminished cognitive function that would interfere with the understanding of study procedures. The Mini-Mental Status Exam (MMSE) will be administered to ensure that participants are free of cognitive impairment that would compromise study participation. MMSE <18 will be excluded.
结局指标
主要结局
Pressure Pain Assessment
时间窗: 1. On Day 1 (Baseline) 2. On Day 4 (post therapy)
Pressure Pain Threshold. A handheld probe (Algomed, Medoc) with a small (less than ½ inch wide) rubber tip will be used to apply pressure to the participant's forearm and shoulder. The pressure will slowly increase, and the participant will be asked to click a button when they first feel pain as a result of the pressure stimulation. The pressure will be removed as soon as the participant presses this button. This particular algometer will be used because it provides the examiner with visual feedback to maintain a consistent application rate, which is critical for maintaining high inter-examiner reliability. To assess the pressure pain threshold, the examiner will apply a constant rate of pressure, and the participant will be instructed to press a button when the sensation first becomes painful, at which time the device records the pressure in kilopascals. Higher kilopascals would suggest less pressure pain.
Thermal (Heat) pain
时间窗: 1. On day 1 (Baseline) 2. On day 4 (Post therapy)
Thermal (Heat) (Threshold, pain, and tolerance) will be assessed using TSA2 Air device from Medoc: A slowly increasing heat stimulus that the participant can terminate by pressing a button when it becomes painful or intolerable. The participant would press the button when they first feel warm (threshold), pain, or can no longer tolerate the heat. Lower heat indices indicate higher thermal sensitivity.
Thermal (Cold) Pain
时间窗: 1. On day 1 (Baseline) 2. On day 4 (Post therapy)
Thermal (Cold) (Threshold, pain, and tolerance) will be assessed using TSA2 Air device from Medoc: A slowly decreasing cold stimulus that the participant can terminate by pressing a button when it becomes painful or intolerable. The participant would press the button when they first feel cold (threshold), pain, or can no longer tolerate the cold. Higher cold indices indicate higher thermal sensitivity.
Temporal Heat Summation
时间窗: 1. On day 1 (Baseline) 2. On Day 4 (Post therapy)
Temporal heat summation will be measured using TSA2 Air device. A series of 5 brief heat pulses (about 2 seconds in duration) will be given, and the participant will be asked to rate how painful each heat pulse feels on a scale from 0 to 100. These heat pulses will be repeated at different temperatures (44° C, 46° C, and 48° C). The participant can stop the procedures at any time so that they do not experience unacceptable pain. Greater pain ratings indicate more pain
Conditioned Pain Modulation
时间窗: 1. On day 1 (Baseline) 2. On day 4 (Post Therapy)
Conditioned pain modulation (CPM) will be tested by TSA2 Air Device. The standard thermode will be placed on the left hand, and the heat pain rating will be assessed at 46 degrees. Then the right hand will be immersed in cold water for 30 seconds. The Heat pain test will be performed again on the left hand to assess Pain modulation. A normal response would indicate a decrease in heat pain on the left hand after immersing the right hand in cold water.
Conditioned Pain Modulation
时间窗: 1. On day 1 (Baseline) 2. On day 4 (Post Therapy)
Conditioned pain modulation (CPM) will be tested by TSA2 Air Device. The standard thermode will be placed on the left hand, and the heat pain rating will be assessed at 46 degrees. Then the right hand will be immersed in cold water for 30 seconds. The Heat pain test will be performed again on the left hand to assess Pain modulation. A normal response would indicate a decrease in heat pain on the left hand after immersing the right hand in cold water.
Pressure Pain Assessment
时间窗: 1. On Day 1 (Baseline) 2. On Day 4 (post therapy)
Pressure Pain Threshold. A handheld probe (Algomed, Medoc) with a small (less than ½ inch wide) rubber tip will be used to apply pressure to the participant's forearm and shoulder. The pressure will slowly increase, and the participant will be asked to click a button when they first feel pain as a result of the pressure stimulation. The pressure will be removed as soon as the participant presses this button. This particular algometer will be used because it provides the examiner with visual feedback to maintain a consistent application rate, which is critical for maintaining high inter-examiner reliability. To assess the pressure pain threshold, the examiner will apply a constant rate of pressure, and the participant will be instructed to press a button when the sensation first becomes painful, at which time the device records the pressure in kilopascals. Higher kilopascals would suggest less pressure pain.
Temporal Heat Summation
时间窗: 1. On day 1 (Baseline) 2. On Day 4 (Post therapy)
Temporal heat summation will be measured using TSA2 Air device. A series of 5 brief heat pulses (about 2 seconds in duration) will be given, and the participant will be asked to rate how painful each heat pulse feels on a scale from 0 to 100. These heat pulses will be repeated at different temperatures (44° C, 46° C, and 48° C). The participant can stop the procedures at any time so that they do not experience unacceptable pain. Greater pain ratings indicate more pain
Thermal (Heat) pain
时间窗: 1. On day 1 (Baseline) 2. On day 4 (Post therapy)
Thermal (Heat) (Threshold, pain, and tolerance) will be assessed using TSA2 Air device from Medoc: A slowly increasing heat stimulus that the participant can terminate by pressing a button when it becomes painful or intolerable. The participant would press the button when they first feel warm (threshold), pain, or can no longer tolerate the heat. Lower heat indices indicate higher thermal sensitivity.
Thermal (Cold) Pain
时间窗: 1. On day 1 (Baseline) 2. On day 4 (Post therapy)
Thermal (Cold) (Threshold, pain, and tolerance) will be assessed using TSA2 Air device from Medoc: A slowly decreasing cold stimulus that the participant can terminate by pressing a button when it becomes painful or intolerable. The participant would press the button when they first feel cold (threshold), pain, or can no longer tolerate the cold. Higher cold indices indicate higher thermal sensitivity.
次要结局
- Measuring endogenous opioids in peripheral immune cells.(1. On day 1 (Baseline) 2. On day 4 (Post Therapy))
- McGill Pain Questionnaire-Short Form(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Brief Pain Inventory(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Present Pain Index(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Visual Analogue scale(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- PHQ-9(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- GAD-7(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Vascular Reactivity Index (VRI)(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Measuring Endogenous Opioids in Plasma(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Measuring Inflammatory cytokines in Plasma(1. On Day 1 (Baseline) 2. On Day 4 (Post Therapy))
- McGill Pain Questionnaire-Short Form(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Brief Pain Inventory(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Present Pain Index(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Visual Analogue scale(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- PHQ-9(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- GAD-7(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Vascular Reactivity Index (VRI)(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Measuring Endogenous Opioids in Plasma(1. On day 1 (Baseline) 2. On day 4 (Post therapy))
- Measuring Inflammatory cytokines in Plasma(1. On Day 1 (Baseline) 2. On Day 4 (Post Therapy))
- Measuring endogenous opioids in peripheral immune cells.(1. On day 1 (Baseline) 2. On day 4 (Post Therapy))
研究者
Dr. Saurabh Aggarwal
Associate Professor
Florida International University