The Warmth, Anticipation, Sensation, Aversion, and Body-part Imaging Study

Overview

This functional magnetic-resonance imaging study of the brain will feature a within-subject crossover design to investigate the effects of a placebo cream on painful thermal stimulation rendered upon eight body sites. The investigators aim to 1.) improve the understanding of how the brain represents thermal pain responses somatotopically (i.e., across different body-sites) 2.) to test these brain representations with and without the presence of a pain-targeted placebo intervention, and 3.) to examine how these brain representations change prior to vs. during the delivery of thermal pain. They predict that placebo cream will downregulate the intensity of aversive brain activity representations, and to a lesser degree, sensation and somatotopic representations, both prior to and during painful thermal stimulation.

Background: Pain is a significant problem within and outside of clinical contexts, and understanding the phenomenon is imperative for optimizing patient care and understanding the efficacy of pain treatment. At the same time, pain anxiety handicaps behavior and productivity, impedes the adoption of healthy behaviors and proper healthcare delivery, and is implicated in the development and maintenance of chronic pain disorders. Pain is commonly perceived as a simplistic attention-capturing stimulus response homeostatic monitoring system that serves a tissue-protective function. Contemporary research, however, promotes a process model of pain that goes beyond simple transmission of a nociceptive signal from a transduced stimulus to include aspects of physiological modulation (e.g., regulatory brain activity from midbrain and brainstem, endogenous and exogenous opioids, and experiential perception (e.g., perceptual brain activity from S1, PFC, thalamus, S2, insula, and thalamus, perceptual exercises such as body vision. Clearly, accurate understanding of pain requires require combining signals across brain regions and networks Our lab, using machine-learning based multivoxel pattern analysis (MVPA) have trained several now widely-used whole-brain neural signatures for pain experience using thermal pain delivery devices (e.g., Neural Pain Signature \[NPS\]), as well as pain-related processes such as viewing pictures of others in pain (Vicarious Pain Signature \[VPS\]), and imagining being romantically rejected. Pursuit of this line of work has revealed these signatures are sensitive and specific to the type of pain it was developed for, yet generalizable enough to work in samples and pain modalities it was not developed in. For example, NPS is specific to somatic pain, and rises and falls with levels of somatic pain of many types, including thermal pain, mechanical pain, and electric shock, but does not track vicarious pain. Our existing signatures do not respond to psychological changes in pain, which is believed to be necessary components for understanding pain hyper- and hypo-algesia as well as the placebo effect. The placebo effect is a powerful demonstration of the effects of the psychological pain context on pain experience. The effect may be directly attributable to emotional and attentional processing. Pain processing shifts from nociceptive somatosensory to emotional during chronification of pain and there is ample evidence that anxiety and stress modulate the amounts of pain reported, the degree of treatment and attention requested, and the degree of pain analgesia experienced upon application of placebo. This evidence suggests that aversive processing of incoming stimuli may play a role in the pain experience. Placebo effects may also simply be somatotopically attention driven, as one previous non fMRI study has suggested. The basic mechanisms of placebo effects on pain anticipation and pain anxiety, and how they relate to placebo effects on pain, are still unknown. Understanding how each of subcomponents of pain -- theoretically separable as the detection of incoming sensation, aversive experiencing, and somatotopic location -- is affected by a placebo treatment may elucidate important facts about pain. This includes how pain is anticipated, processed, and subsequently regulated, providing insight into the nature of pain anxiety and how information should be delivered to mitigate pain. Such knowledge is essential for enhancing existing therapies and creating more nuanced and targeted ones for debilitating pain-related maladies such as chronic pain disorders, and important therapeutic procedures that may cause pain (e.g., surgical or dental). Experimental Design: The first hour of fMRI scanning aims to isolate sensation, aversiveness, and somatotopic subcomponents of pain into individual neural signatures. We will do so by subjecting participants at random to stimulations of painful heat and non-painful warmth on various body sites -- left and right masseter, midline chest, midline trunk, left and right forearm, and left and right upper-calf -- as well as listen to an aversive sound (e.g., scratching chalkboard). Participants will also be asked at various times to follow instructions to imagine themselves feeling intense heat pain at a randomly designated body site. In the second hour of fMRI scanning, we will examine to what degree the identified isolated subcomponents of sensation, aversiveness, and somatotopy respond to placebo treatment for heat pain (i.e., the application of an inert cream coinciding with either an instruction that the participant will be given "an analgesic cream" relative to "a control cream with no effect").