Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Modulation in Individuals With Parkinson's Disease in the Off State
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in Conditioned Pain Modulation
研究概览
简要总结
Parkinson's Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. Pain is a significant symptom in PD, affecting a large percentage of patients and impacting their quality of life. The mechanisms of pain in PD involve complex changes in pain-modulating pathways, including dopaminergic and non-dopaminergic systems.
To address the lack of pain management strategies, the investigators propose exploring non-pharmacological therapies like transcranial direct current stimulation (tDCS). tDCS is a safe and non-invasive technique that modulates neuronal activity. It has shown positive effects on pain processing in healthy individuals and chronic pain patients, but its potential for PD-associated pain remains largely unexplored.
The primary motor cortex (M1) is a target for tDCS as it is believed to influence pain processing in other brain regions involved in sensory and emotional aspects. Initial studies suggest the benefits of tDCS in PD, including enhanced motor potentials and potential modulation of dopaminergic pathways. However, there are currently no published studies specifically investigating the effects of tDCS on PD-related pain, highlighting the need for further research.
A proof-of-concept trial is proposed to examine the effects of a single tDCS session on M1 in PD patients during the OFF state (without medication) and after taking dopaminergic medication. The study aims to assess the pain-relieving effects of tDCS in PD and explore potential synergies between tDCS and dopaminergic medication. By better understanding the impact of tDCS on pain relief in PD, this research may offer insights into alternative non-pharmacological approaches for managing pain in PD.
详细描述
Parkinson's Disease (PD) is a complex progressive neurodegenerative disorder. It is the second most common neurodegenerative disease, with a prevalence of 4.1 to 4.6 million people over the age of 50. It is estimated that these numbers will increase to 8.7 to 9.3 million by the year 2030.
PD is multisystemic and include both motor and non-motor symptoms. These symptoms can fluctuate throughout the day, leading PD patients to frequently experience two distinct states: the "on" state, when dopaminergic medication is active in their system, and the "off" state, which occurs when there is no medication concentration in the body, resulting in more severe symptoms.
Pain in PD is a highly relevant symptom that significantly impacts patients' quality of life, with a prevalence of up to 85% and moderate to severe intensity reported in 42% of individuals. Additionally, in Spain, the prevalence of PD-associated pain has significantly increased following the COVID-19 pandemic, with up to 50% of PD patients reporting daily pain. Moreover, pain in PD is often underreported, emphasizing the need to investigate its mechanisms and treatment.
The pathophysiological mechanisms of pain in PD are complex. In general, PD can lead to alterations in peripheral transmission, sensory-discriminative processing, pain perception, and interpretation at multiple levels, due to neurodegenerative changes in both dopaminergic and non-dopaminergic pain-modulating pathways. This dysregulation of the dopaminergic system can impact the experience of pain directly by enhancing nociceptive signals and indirectly by influencing expectations and the interpretation of such signals. However, it is considered that there is no specific pain center in PD patients but rather a pain matrix involving various brain structures.
Given the multiple central structures affected and their consequent pathophysiological mechanisms in PD-associated pain, there is a wide variety of clinical manifestations. These include musculoskeletal pain, generalized central chronic pain, visceral pain, pain related to "on-off" fluctuations, dystonic-dyskinetic pain, nocturnal immobility-related pain or restless legs syndrome, orofacial pain, inflammation or edema-related pain, and radicular pain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Triple-blind criteria will be achieved by identic collocation of the electrodes in both conditions and by activating the "double-blind" option in the Starstim tDCS® Software (Neuroelectrics Inc, Barcelona, Spain) that allows concealing the protocol by writing a neutral number. The evaluator, not allowed to stay in the same room while the interventions, will conceal the protocols with the neutral number and the therapist will read it in the envelope, ignoring which number coincides with each intervention. At the end of the second session, patients will be asked whether they received the order 1.active-2.sham or 1.sham-2.active, to assess the blinding success. The statistician will also be blinded through the mentioned neutral numbers. Unblinding will be permissible when any event could suppose a risk to the patient's health.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Idiopathic Parkinson´s Disease.
- •Presence of Parkinson´s Disease-related pain in the off-state.
- •Neuroimaging study without previous pathologies.
- •Score > 5 in transfers (bed to chair and back) item in Barthel Index.
- •Score = or > 26 in Montreal Cognitive Assessment (MoCA).
- •Tolerability for the application of electrotherapy.
- •Able to provide informed consent to participate in the study
- •Pain intensity >= 3 in Visual Analogue Scale or equivalent.
排除标准
- •Neurologic disease different from PD.
- •Pain non-related to PD.
- •Dermatologic problems, wounds, or ulcers in the electrode's application area.
- •Presence of implants or metal pieces in the head.
- •Presence of cardiac pacemaker, vagal, brain or transcutaneous stimulators, medication pumps, ventriculoperitoneal shunts or aneurysm clips.
- •Significative difficulties in language.
- •History of alcohol or drugs abuse.
- •Non-controlled medical problems.
- •Pregnancy.
研究组 & 干预措施
Active Transcranial Direct Current Stimulation and dopaminergic medication
Active Transcranial Direct Current Stimulation (atDCS) will be applied over the Primary Motor Cortex (M1) contralateral to pain if it is unilateral, or always on the left M1 if pain is bilateral. It will consist of 1 session of 20 minutes of conventional stimulation (anode over M1) at 2 mA. It will be applied in the OFF state (i.e., >12h after the last medication intake). Lately, patients will take its usual dopaminergic medication.
干预措施: Active Transcranial Direct Current Stimulation (Device)
Active Transcranial Direct Current Stimulation and dopaminergic medication
Active Transcranial Direct Current Stimulation (atDCS) will be applied over the Primary Motor Cortex (M1) contralateral to pain if it is unilateral, or always on the left M1 if pain is bilateral. It will consist of 1 session of 20 minutes of conventional stimulation (anode over M1) at 2 mA. It will be applied in the OFF state (i.e., >12h after the last medication intake). Lately, patients will take its usual dopaminergic medication.
干预措施: Sham Transcranial Direct Current Stimulation (Device)
Active Transcranial Direct Current Stimulation and dopaminergic medication
Active Transcranial Direct Current Stimulation (atDCS) will be applied over the Primary Motor Cortex (M1) contralateral to pain if it is unilateral, or always on the left M1 if pain is bilateral. It will consist of 1 session of 20 minutes of conventional stimulation (anode over M1) at 2 mA. It will be applied in the OFF state (i.e., >12h after the last medication intake). Lately, patients will take its usual dopaminergic medication.
干预措施: Dopaminergic medication (Drug)
: Sham Transcranial Direct Current Stimulation and dopaminergic medication
Sham Transcranial Direct Current (s-tDCS) will be applied over the Primary Motor Cortex with the same procedure, during 1 session of 20 minutes of conventional stimulation. It will be applied in the OFF state (i.e., >12h after the last medication intake). Lately, patients will take its usual dopaminergic medication.
干预措施: Active Transcranial Direct Current Stimulation (Device)
: Sham Transcranial Direct Current Stimulation and dopaminergic medication
Sham Transcranial Direct Current (s-tDCS) will be applied over the Primary Motor Cortex with the same procedure, during 1 session of 20 minutes of conventional stimulation. It will be applied in the OFF state (i.e., >12h after the last medication intake). Lately, patients will take its usual dopaminergic medication.
干预措施: Sham Transcranial Direct Current Stimulation (Device)
: Sham Transcranial Direct Current Stimulation and dopaminergic medication
Sham Transcranial Direct Current (s-tDCS) will be applied over the Primary Motor Cortex with the same procedure, during 1 session of 20 minutes of conventional stimulation. It will be applied in the OFF state (i.e., >12h after the last medication intake). Lately, patients will take its usual dopaminergic medication.
干预措施: Dopaminergic medication (Drug)
结局指标
主要结局
Change in Conditioned Pain Modulation
时间窗: From baseline to immediately post dopaminergic medication
Assesses the descending pain modulatory system. The Pain Pressure Threshold will be assessed in the middle ofthe distal phalanx of the thumb with ta handheld algometer, corresponding to the first test stimulus. Afterward, the patient will immerse the contrary hand up to the wrist into stirred ice-cold water (0-4º) maintaining it for 3 minutes, corresponding to the conditioning stimulus. If the pain is unbearable before the 3 minutes, the patient will be able to remove his/her hand. Immediately after removing the hand, a second Pain Pressure Threshold measure will be performed in the same place as the first one, corresponding to the second test stimulus. After 1-minute rest, a third Pain Pressure Threshold will be measured to assess the Conditioned Pain Modulation residual functioning.
Changes in Pain Pressure Threshold
时间窗: From baseline to immediately post dopaminergic medication
Two Pain Pressure Thresholds will be measured by a handheld algometer, one over the most painful area (peripheric hyperalgesia) and the other one over the middle of the distal phalanx of the thumb (central hyperalgesia). The Pain Pressure Threshold will be applied with the algometer perpendicular to the skin increasing at a rate of 1 kg/s until the first sensation of pain. 3 measures with 30-seconds rest between pulses will be performed, taking the average as Pain. Pressure Threshold.
Changes in Visual Numeric Pain Rating Scale
时间窗: From baseline to immediately post dopaminergic medication
It will be used to measure pain intensity due to its high discriminatory power. The scale assesses pain intensity using numbers or words through various types of scales ranging from 0 to 10. Pain rating ranges from 0 (no pain), 1-3 (mild pain, mild discomfort or irritation, slight impairment in daily activities), 4-6 (moderate pain, significant impairment in daily activities), and 7-10 (severe pain, inability to perform daily activities).
Changes in Global Rating of Change
时间窗: From baseline to immediately post dopaminergic medication
It will be used to measure the self-perceived change in the patient's pain state. Its main objective is to quantify the extent to which a patient has improved or worsened over a specific period of time. It involves a single question asked to the patient to rate their change compared to the pre-intervention state, and the scores will range from -7 (much worse than before), through 0 (same as before), to +7 (much better than before).
次要结局
- Changes in Unified Parkinson´s Disease Rating Scale(From baseline to immediately post dopaminergic medication)
- Changes in Brain Symmetry Index in electroencephalography(From baseline to immediately post dopaminergic medication)
- Changes in Finger tapping task(From baseline to immediately post dopaminergic medication)