Greater fear of visceral pain contributes to differences between visceral and somatic pain in healthy women

Abstract

This functional magnetic resonance imaging study addressed similarities and differences in behavioral and neural responses to experimental visceral compared with somatic pain stimuli and explored the contribution of fear of pain to differences between pain modalities. In N = 22 healthy women, we assessed blood oxygen level-dependent responses to rectal distensions and cutaneous heat stimuli matched for perceived pain intensity. Fear of pain and pain unpleasantness were assessed before and after scanning. Visceral pain was more fear evoking and more unpleasant, and trial-by-trial intensity ratings failed to habituate across trials (all interactions modality × time: P < 0.01). Differences in fear of pain and pain intensity independently contributed to greater visceral pain unpleasantness (combined regression model: R(2) = 0.59). We observed joint neural activations in somatosensory cortex and frontoparietal attention network (conjunction analysis: all pFWE <0.05), but distensions induced greater activation in somatosensory cortex, dorsal and ventral anterior insula, dorsal anterior and midcingulate cortices, and brainstem, whereas cutaneous heat pain led to enhanced activation in posterior insula and hippocampus (all pFWE <0.05). Fear of visceral pain correlated with prefrontal activation, but did not consistently contribute to neural differences between modalities. These findings in healthy women support marked differences between phasic pain induced by rectal distensions vs cutaneous heat, likely reflecting the higher salience of visceral pain. More studies with clinically relevant pain models are needed to discern the role of fear in normal interindividual differences in the response to different types of pain and as a putative risk factor in the transition from acute to chronic pain.

The Role of Chronic Stress in Normal Visceroception: Insights From an Experimental Visceral Pain Study in Healthy Volunteers

“…In healthy individuals, we recently observed pharmacologically increased cortisol levels to induce a reduction in visceral pain thresholds and to affect the formation of pain-related emotional memories (8). Importantly, these effects appeared to be specific to the visceral domain and were not observed for somatic stimuli of identical intensities, in line with prior research on distinct mechanisms underlying the processing of visceral and somatic pain (39)(40)(41)(42), and suggesting that visceroception might be particularly vulnerable to stress and stress mediators. Our findings expand this evidence to the dimension of chronic stress, with putative clinical implications for vulnerability and resilience in health and in disorders of gut-brain communication.…”

Sex Differences Linking Pain-Related Fear and Interoceptive Hypervigilance: Attentional Biases to Conditioned Threat and Safety Signals in a Visceral Pain Model

“…Visceral pain is of high clinical relevance, specifically in conditions of the gut-brain axis like irritable bowel syndrome (IBS). Compared to other types of exteroceptive pain, visceral pain is considered to be characterized by a unique biological salience, as supported by greater visceral pain-related fear and enhanced pain-related learning (12,13), making this a suitable preclinical model to study pain-related attentional biases. While numerous studies addressed attentional biases toward threat only, safety cues signaling the absence of an aversive event were also found to induce attentional biases (14) and are prioritized under threatening conditions (15).…”

The gut–brain axis in health neuroscience: implications for functional gastrointestinal disorders and appetite regulation

“…50 Studies comparing the brain response to visceral and somatic pain directly are sparse, but the best available study suggests a pattern of commonalities as well as specificities. 51 The brain regions commonly activated by both visceral and somatic stimulations, such as the insula and ACC/MCC, can be more broadly engaged by spinal lamina I afferent input to the brain, signaling any potential threat to the organism's homeostasis. 46 Therefore, the network commonly activated in pain studies, previously referred to as the "pain neuromatrix," may have to be reconceptualized as a salience network that is engaged in response to any salient stimulus, not limited to pain.…”