Neural and Psychological Mechanisms of Pain Perception
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 550
- 试验地点
- 1
- 主要终点
- BOLD response in brain regions of interest measured using fMRI
研究概览
简要总结
Background:
- Painful stimuli cause changes in a network of brain regions called the "Pain Matrix." But most of these regions respond to many other stimuli, not just pain. Researchers want to understand how different factors influence pain. They want to test what happens when people expect different levels of pain and receive treatments that can modify pain. They want to see if these factors influence decisions about pain and how the body responds to it. They also want to compare pain with responses like taste and vision.
Objectives:
- To better understand how pain and emotions are processed and influenced by psychological factors.
Eligibility:
- Healthy volunteers ages 18-50.
Design:
- This study requires 1 to 2 clinic visits that last 1 to 3 hours.
- Participants will be screened with medical history and physical exam.
- Some participants will have one or more magnetic resonance imaging (MRI) scans of their brain. For MRI, participants will lie on a table that slides in and out of a cylinder. The scanner makes loud knocking noises. They will get earplugs.
- Participants' heart activity will be recorded with electrocardiogram. Their pulse, sweating, and breathing will be monitored.
- Some participants will take a taste test. Others may perform simple tasks. Others may receive pain in their arm, leg, or hand. The pain will come from heat or electric shocks. Others may judge pain using a topical pain-relieving cream. Some of these tests may be given during MRI.
- Participants will fill out questionnaires.
- The study will last 3 years.
详细描述
Objective
Pain is one of the most important signals for an organism s survival. The pathways that transfer noxious input from the periphery to the central nervous system are highly conserved across human and animal models. In humans, the ultimate experience of pain is also highly influenced by psychological factors. For example, the placebo effect leads to robust pain relief and can influence responses to noxious stimuli in the human brain. However, the psychological and neurobiological mechanisms by which psychological factors influence pain remain largely unknown.
Pain can be modulated by explicit beliefs about treatments, prior experience and learning, interpersonal processes that support the patient-provider relationship, and contextual factors related to the treatment environment. In the proposed series of experiments, we will systematically investigate the neural and psychological mechanisms that mediate the effects of these factors on acute pain. We will focus on expectations, attention, emotion, conditioning/associative learning, and social factors. These experiments will principally use functional magnetic resonance imaging (fMRI) and psychophysiological measurements, as well as behavioral assays and self-reports. We will examine the effects of different types of pain-related expectations on decisions about pain as well as responses in the brain and periphery. We will also compare acute pain with other hedonic and perceptual processes. This will allow us to distinguish processes that are unique to pain perception from those that are not specific to pain, such as processes involved in perception and decision-making across domains.
Together, the proposed series of experiments aim to elucidate the psychological, neurobiological, and physiological mechanisms that modulate pain. This, in turn, can identify targets for pain treatment and inform mechanistic studies of altered pain processing in clinical populations.
Study Population
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years(Adult)
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA:
- •Between 18 and 50 years old
- •Fluent in English
- •Able to provide written informed consent.
排除标准
- •(all sub-studies):
- •Unable to comply with study procedures or follow-up visits.
- •Has a major medical condition or medical history that in a clinician's assessment could affect heat sensitivity, pain thresholds, or ability to comply with study procedures. This may include cardiovascular, autonomic, or neurological conditions, including stroke, blindness, deafness, a history of brain damage, or a chronic systemic disease (e.g., diabetes).
- •Has a current mood disorder, anxiety disorder, or substance use disorder, or has a history of psychosis, hospitalization for a mental health condition, or recurrent psychiatric episodes.
- •Has a medical condition that in a clinician's assessment might affect somatosensation (e.g., Raynaud's disease, peripheral neuropathy, or circulatory disorder).
- •Has a current chronic pain condition or has had chronic pain in the past (painful condition lasting more than six months).
- •Has a dermatological condition affecting the testing region such as scars, burns, or recent tattoos that might influence cutaneous sensibility.
- •Regular use of prescription medication that has a significant effect on pain or heat perception. Excluded medications include central-acting agents such as opiates (morphine, tramadol), antidepressants (amitriptyline, duloxetine, milnacipran), anticonvulsants (gabapentin, pregabalin), anxiolytics (barbituates, benzodiazepines), hypnotics (zolpidem, sodium oxybate), antipsychotics (valproate, lithium, olanzapine), antimigraine agents (sumatriptan, ergotamine), and muscle relaxants (cyclobenzaprine, carisoprodol). Use of analgesic medications, such as non-steroidal anti-inflammatories, salicylates, and acetaminophen, taken on an "as needed" basis is acceptable as long as the last dose taken was within 5 half-lives of testing.
- •Is pregnant.
- •NIH staff member who is a subordinate/relative/co-worker of any investigator on the protocol.
- •EXCLUSION CRITERIA (fMRI sub-studies):
- •Individuals with conditions that could pose a risk relating to the safety of the fMRI procedure or pain stimulation will be excluded from the MRI portion of the protocol, but may participate in the non-fMRI sessions (with the exception of pregnant women). Such conditions include:
- •Those with ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip, implanted neural stimulator, cochlear implant, ocular foreign body.
- •Those with an abnormality on a structural MRI.
- •Those with an implanted cardiac pacemaker or auto-defibrillator.
- •Those with an insulin pump.
- •Those with irremovable body piercing.
- •Pregnant women (based on urine test completed within 24 hours prior to scan).
- •Individuals who are left-handed (based on self-report or score on handedness questionnaire) will be excluded from fMRI substudies.
- •EXCLUSION CRITERIA (placebo analgesia sub-studies):
- •Participation in an NIH study of analgesia, as gleaned from CRIS.
研究组 & 干预措施
Substudy 1: Instructed subjects
Participants are instructed about outcomes
干预措施: Instructions (Behavioral)
Substudy 2: sugar group
Participants learn about sugar outcomes through conditioning
干预措施: Thermal Pain (Behavioral)
Substudy 3: healthy volunteers
All participants experience all outcomes, within subjects designs
Substudy 2: heat group
Participants learn about heat outcomes through conditioning
干预措施: Thermal Pain (Behavioral)
Substudy 1: Uninstructed subjects
Participants learn through experience
干预措施: Instructions (Behavioral)
Substudy 5: healthy volunteers
Participants experience both placebo and cue-based expectations within subjects
干预措施: Placebo instructions (Behavioral)
Substudy 4: healthy volunteers
Participants are instructed to attend toward or away from the stimulus
干预措施: Attention (Behavioral)
Substudy 2: salt group
Participants learn about salt outcomes through conditioning
干预措施: Thermal Pain (Behavioral)
结局指标
主要结局
BOLD response in brain regions of interest measured using fMRI
时间窗: During the study visit in response to painful and non-painful stimuli.
FMRI substudies proceed following behavioral substudies. We measure brain responses in anticipation and response to painful and non-painful stimuli.
Physiological responses (heart rate, skin conductance, respiration, pupil dilation, eye gaze position)
时间窗: During the study visit in response to painful and non-painful stimuli.
In behavioral and fMRI experiments, we measure autonomic responses in anticipation and response to painful and non-painful stimuli using non-invasive measures.
Pain perception (pain ratings)
时间窗: During the study visit in response to painful stimuli.
Substudies of pain collect pain ratings using a visual analogue scale, either verbally or via computer.
次要结局
- Questionnaire measures (e.g. State-trait anxiety index, Fear of Pain questionnaire, Intolerance of Uncertainty questionnaire, McGill Pain Questionnaire)(Trait measures are collected during initial screening visit ; State measures are collected on every visit)
