Neural and Psychological Mechanisms of Pain Perception

Overview

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.

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 We plan to recruit 500 healthy volunteers between age 18 and 50. Design The aim of the proposed series of experiments is to understand how expectations, attention, and emotion influence acute pain. We will manipulate expectations about noxious stimuli using associative learning and verbal instructions, in both within-subjects and between-groups designs. We will measure decisions about pain experience (self-report) as well as neural and physiological responses to noxious stimuli that cause pain. We will combine computational modeling with advanced neuroimaging analyses to isolate the neural and psychological mechanisms that mediate the effects of expectations, attention, and emotion on subjective pain. To determine the specificity of these mechanisms, we will compare acute pain modalities (e.g., thermal pain versus shock-induced pain), and we will contrast pain with other hedonic and perceptual domains (e.g., taste). Outcome measures Dependent variables for all experiments will include decisions about pain and/or other percepts (e.g., sweetness of a taste) measured with visual analogue scales, reaction time, physiological responses (e.g., skin conductance, pupil dilation), and/or BOLD activation in regions of interest. We are specifically interested in processes within the network of regions known to be involved in pain processing (pain-processing network, PPN), as well as responses in the prefrontal cortex (PFC), ventral striatum (VS), and amygdala. We hypothesize that nociceptive stimuli and pain ratings will be associated with unique patterns of activation within the PPN, whereas responses in regions associated with value, executive function, and decision-making will be common across outcomes.