Sensitivity To Pain: Psychological Traits And Associated Brain Structures

Some people feel pain more quickly or more intensely than others, and researches have implicated differences in both psychological traits and brain structures as influences on individual differences in pain sensitivity. The purpose of this thesis was to elucidate, with more specificity,(1) psychological and (2) neural correlates of pain perception.Pain perception, including the sensory-discriminative component (intensity) and motivational-affective component (unpleasantness), may be influenced by psychological factors such as pain-related fear, general psychological distress, and somatization. Although there is considerable evidence that pain-related fear influences pain perception and the development and maintenance of chronic pain lasting for more than three months, studies have not typically assessed relative contributions of pain-related fear, general psychological distress and somatization on pain perception. One methodological concern with research in this area has been a reliance on using individual scales to measure complex constructs such as psychological distress and pain-related fear. Furthermore, a majority of studies have used chronic pain samples, so it is not clear whether possible elevations in somatization, psychological distress and pain-related fear influenced pain perception or resulted from experiences of ongoing pain.Two cross-sectional studies were designed to clarify psychological factors critical to pain perception within pain-free samples of university students. Study1was designed to evaluate the structure and distinctiveness of somatization, psychological distress and pain-related fear using multiple measures to represent each factor instead of single scales. In Study2, the impact of each of these psychological dimensions on pain perception was evaluated within a laboratory pain paradigm. The focus of Study3was upon elucidating brain structure correlates underlying pain sensitivity.In Study1,653university students (455women,198men) completed a battery of self-report measures including five pain-related fear scales, three measures of psychological distress not specifically related to pain, and two somatization scales. Exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) were performed, respectively, on random equal subsets of the total sample to determine whether initially derived factor solutions were replicable in a new group. EFA results identified a three factor solution consistent with the psychological constructs above. CFA confirmed that this solution had an acceptable fit for the data.In Study2,105participants (74women,31men) completed the same questionnaire battery and completed a Cold Pressor Test (CPT) involving the immersion of their non-writing hand in ice water for as long as possible up to a five minute maximum, in a counter-balanced manner. Hierarchical regression models and moderation/mediation analyses were conducted to assess effects of these three psychological factors on four indices of pain perception (i.e., threshold at which pain was first perceived, tolerance based on immersion time, and self-reported intensity and unpleasantness). The main results of Study2were as follows:(1) the pain-related fear and psychological distress factors significantly and positively predicted both pain intensity and pain unpleasantness; however, the impact of psychological distress were fully mediated by pain-related fear,(2) higher scores on the pain-related fear predicted lower pain tolerance levels to a marginally-significant extent (p=0.097) while neither somatization nor psychological distress had effects, and (3) among participants reporting high levels of pain-related fear, high levels of somatization were related to low levels of pain unpleasantness.Taken together, results of Study1and Study2indicated that pain-related fear, rather than psychological distress or somatization, was the key dimension associated with exaggerated pain perception, especially regarding subjective intensity and unpleasantness of pain. Mediating effects of pain-related fear may have indicated associations between general psychological distress and subjective pain experiences are influenced primarily through their shared relations with pain-specific emotional responses. The negative association between somatization and subjective pain experience may have reflected a tendency to focus on somatic symptoms as a protective adaptation that helped to maintain homeostasis, among vulnerable individuals, specifically those who were highly pain-fearful during exposure to noxious stimulation.Regarding the second focus of this thesis, researchers have only recently begun to examine brain structure correlates underlying pain sensitivity. Restricted within the pain matrix, a distributed brain network classically identified by activation pattern in response of nociceptive stimulation, two studies yielded unexpected results indicating the pain matrix is more closely correlated with non-painful sensory detection sensitivity than pain sensitivity (Elsenbruch et al.,2013; Erpelding, Moayedi,&Davis,2012). Furthermore, structural (Emerson et al.,2014) and functional (Goffaux, Girard-Tremblay, Marchand, Daigle,&Whittingstall,2013) whole brain analyses emphasized robust associations of the Default Mode Network (DMN) with pain sensitivity. Notably, only the left precuneus (PCu) of DMN emerged in the functional analysis of relations between pain-induced ERP responses and pain sensitivity. Additionally, given recent evidence illustrating that functional connectivity between the pain matrix and DMN predicts pain detection (Witting et al.,2001) and chronic pain development (Napadow, Kim, Clauw,&Harris,2012; Napadow et al.,2010), prior neglect of the DMN and its interactions with the pain matrix is an important gap that warrants examination in clarifying how pain perception arises. Study3was designed to assess brain structure correlates of pain sensitivity by contrasting non-pain and painful stimulation across the pain matrix and DMN.Eighty pain-free right-handed undergraduates (35women,45men) were recruited for Study3. Following a structural MRI scan, participants received standard psychophysical tests in cold, hot and electro-cutaneous modalities to obtain indices of sensitivity to both non-painful and painful stimulation. Voxel-based morphometry (VBM) analyses were conducted within a unified mask consisting of pain matrix structures and the DMN. Four VBM indices, respectively, measuring gray matter density (GMD), gray matter volume (GMV), white matter density (WMD) and white matter volume (WMV) were analyzed in parallel analyses, using each psychophysical measure as a predictor and controlling for possible confounding variables-age, gender and global average of each VBM indice.With multiple comparisons corrected using the AlphaSim method, results in the thermal modalities indicated some structural correlates of the pain matrix (i.e., thalamus, insula, anterior cingulate cortex, basal ganglia and hippocampus construct) corresponded exclusively with sensitivity to non-painful stimulation, while the left precuneus (PCu) of the DMN was linked exclusively with supra-pain sensitivity. This pattern of double dissociation was present across cold and hot modalities but disappeared for the electro-cutaneous modality. Sensitivity to non-pain electro-cutaneous stimuli was not related to any pain matrix regions or the DMN while sensitivity to painful electro-cutaneous stimulation correlated with a conjunct cluster on amygdale and hippocampus in the pain matrix.In conclusion, pain matrix structures correlated with sensitivity to nonpainful thermal stimuli while the PCu correlated with sensitivity to painful thermal stimulation. Notably, data highlighting the critical role of the precuneus as a correlate of pain sensitivity independently replicated a functional study identifying the precuneus as the sole neural correlate of pain sensitivity. Accordingly, a ’two-stage model’ is proposed to explain how pain matrix structures and the precuneus communicate in the process of pain recognition. Specifically, non-painful sensory representations are processed in pain matrix structures and projected to the precuneus for further integration involving the identification of sensations as "pain". Compatibility of this model with other theories is elaborated in the discussion of Study3.