Pain Sensitive Research Articles

The Influence of Sex and Gender, Gender Ontological Beliefs, and Sexism on Pain Sensitivity Judgments: Implications for Health Care Settings and Beyond

Chronic pain affects at least one in five individuals. Hence, adequate pain judgement is a vital interpersonal skill. Nonetheless, women often face treatment disparities due to biased assessments. Priorly, sex and gender (i.e., biological category vs. cultural representation) have not been investigated separately. Our study was thus designed to disentangle their distinct influence on pain judgments. In an online study, N = 679 participants (73.8% female) were presented with a novel vignettes paradigm including descriptions of fictional gender-stereotypical and counter-stereotypical women and men. Participants were instructed to rate the characters’ pain sensitivity before completing inventories measuring gender ontological beliefs and ambivalent sexism. We found significant interaction effects of observer and character sex, in that higher pain sensitivity was attributed to opposite-sex characters. Men showed a higher sex bias, which was partially mediated by lower social constructionism and higher hostile sexism. We further uncovered a gender bias across observers, in that feminine characters were assumed to be more pain sensitive, irrespective of their sex. Our research underscores the presence of sex and gender biases in pain judgments, even in scenarios with minimal contextual cues. Despite limitations, the findings offer insights for the development of intervention strategies, which might reduce treatment disparities.

Functional Changes of White Matter Are Related to Human Pain Sensitivity during Sustained Nociception.

Pain is considered an unpleasant perceptual experience associated with actual or potential somatic and visceral harm. Human subjects have different sensitivity to painful stimulation, which may be related to different painful response pattern. Excellent studies using functional magnetic resonance imaging (fMRI) have found the effect of the functional organization of white matter (WM) on the descending pain modulatory system, which suggests that WM function is feasible during pain modulation. In this study, 26 pain sensitive (PS) subjects and 27 pain insensitive (PIS) subjects were recruited based on cold pressor test. Then, all subjects underwent the cold bottle test (CBT) in normal (26 degrees temperature stimulating) and cold (8 degrees temperature stimulating) conditions during fMRI scan, respectively. WM functional networks were obtained using K-means clustering, and the functional connectivity (FC) was assessed among WM networks, as well as gray matter (GM)-WM networks. Through repeated measures ANOVA, decreased FC was observed between the GM-cerebellum network and the WM-superior temporal network, as well as the WM-sensorimotor network in the PS group under the cold condition, while this difference was not found in PIS group. Importantly, the changed FC was positively correlated with the state and trait anxiety scores, respectively. This study highlighted that the WM functional network might play an integral part in pain processing, and an altered FC may be related to the descending pain modulatory system.

Association between systemic inflammation and experimental pain sensitivity in subjects with pain and painless neuropathy after traumatic nerve injuries.

Peripheral neuropathies that occur secondary to nerve injuries may be painful or painless, and including a low-grade inflammation and pro-inflammatory cytokines associated with both regeneration and damage of peripheral nerve cells and fibers. Currently, there are no validated methods that can distinguished between neuropathic pain and painless neuropathy. The aim of this study was to search for proinflammatory and anti-inflammatory proteins associated with pain and experimental pain sensitivity in subjects with surgeon-verified nerve injuries in the upper extremities. One hundred and thirty-one subjects [69 with neuropathic pain, NP; 62 with painless neuropathy, nP] underwent a conditioned pain modulation (CPM) test that included a cold pressor task (CPT) conducted with the non-injured hand submerged in cold water (4°C) until pain was intolerable. CPM was assessed by pain ratings to pressure stimuli before and after applying the CPT. Efficient CPM effect was defined as the ability of the individual's CS to inhibit at least 29% of pain (eCPM). The subjects were assigned to one of two subgroups: pain sensitive (PS) and pain tolerant (PT) after the time they could tolerate their hand in cold water (PS<40s and PT=60s) . Plasma samples were analyzed for 92 proteins incorporated in the inflammation panel using multiplex Protein Extension Array Technology (PEA). Differentially expressed proteins were investigated using both univariate and multivariate analysis (principal component analysis-PCA and orthogonal partial least-squares discriminant analysis-OPLS-DA). Significant differences in all protein levels were found between PS and PT subgroups (CV-ANOVA p<0.001), but not between NP and nP groups (p=0.09) or between inefficient CPM (iCPM) and eCPM (p=0.53) subgroups. Several top proteins associated with NP could be detected using multivariate regression analysis such as stromelysin 2 (MMPs), interleukin-2 receptor subunit beta (IL2RB), chemokine (C-X-C motif) ligand 3 (CXCL3), fibroblast growth factor 5 (FGF5), chemokine (C-C motif) ligand 28 (CCL28), CCL25, CCL11, hepatocyte growth factor (HGF), interleukin 4 (IL4), IL13. After adjusting for multiple testing, none of these proteins correlated significantly with pain. Higher levels of CCL20 (p=0.049) and CUB domain-containing protein (CDCP-1; p=0.047) were found to correlate significantly with cold pain sensitivity. CDCP-1 was highly associated with both PS and iCPM (p=0.042). No significant alterations in systemic proteins were found comparing subjects with neuropathic pain and painless neuropathy. An expression of predominant proinflammatory proteins was associated with experimental cold pain sensitivity in both subjects with pain and painless neuropathy. One these proteins, CDC-1 acted as "molecular fingerprint" overlapping both CPM and CPT. This observation might have implications for the study of pain in general and should be addressed in more detail in future experiments.

Test-Retest Reliability of an Adaptive Thermal Pain Calibration Procedure in Healthy Volunteers

Quantitative sensory testing (QST) allows researchers to evaluate associations between noxious stimuli and acute pain in clinical populations and healthy participants. Despite its widespread use, our understanding of QST's reliability is limited, as reliability studies have used small samples and restricted time windows. We examined the reliability of pain ratings in response to noxious thermal stimulation in 171 healthy volunteers (n = 99 female, n = 72 male) who completed QST on multiple visits ranging from 1 day to 952 days between visits. On each visit, participants underwent an adaptive pain calibration in which they experienced 24 heat trials and rated pain intensity after stimulus offset on a 0 to 10 Visual Analog Scale. We used linear regression to determine pain threshold, pain tolerance, and the correlation between temperature and pain for each session and examined the reliability of these measures. Threshold and tolerance were moderately reliable (Intra-class correlation = .66 and .67, respectively; P < .001), whereas temperature-pain correlations had low reliability (Intra-class correlation = .23). In addition, pain tolerance was significantly more reliable in female participants than male participants, and we observed similar trends for other pain sensitive measures. Our findings indicate that threshold and tolerance are largely consistent across visits, whereas sensitivity to changes in temperature vary over time and may be influenced by contextual factors. PerspectiveThis article assesses the reliability of an adaptive thermal pain calibration procedure. We find that pain threshold and tolerance are moderately reliable whereas the correlation between pain rating and stimulus temperature has low reliability. Female participants were more reliable than male participants on all pain sensitivity measures.

Bedside clinical tests to assess sensitization in office workers with chronic neck pain

Objective This study aimed to assess pain sensitization in individual office workers with chronic neck pain through simple bedside quantitative sensory tests (QST) and to associate the findings with pain intensity and pain catastrophizing. Methods One hundred-and-four office workers with chronic neck pain were assessed using pressure pain threshold (PPT) considering pain sensitive if PPTs were lower than 155 kPa in the upper trapezius and 245 kPa in the tibialis anterior. Pain sensitive to temporal summation of pain (TSP) was considered if there was a difference of two points in the visual analogue scale (VAS) comparing the first and last stimulus. Pain sensitive was considered to conditioned pain modulation (CPM) if the CPM-effect was less than −7.5%. Pain intensity and catastrophizing were measured using VAS and with the Pain Catastrophizing Scale. Results There was at least one pain sensitive QST finding in 66 office workers (63.5%). TSP findings were the most common (48.1%), followed by PPT’s (31.7%) and CPM (20.2%). Based on the QST findings, office workers were divided based on the number of individual QST findings, and higher pain intensity and pain catastrophizing scores were found in office workers with one (N = 38, P < 0.05) or two (N = 28, P < 0.05) compared with office workers with no QST findings (N = 38). Conclusion This study demonstrated that most office workers with chronic neck pain exhibit either widespread pressure hyperalgesia, facilitated TSP or impaired CPM, indicating pain sensitization within the central nervous system. This was associated with increased clinical pain and pain catastrophizing rumination scores.

Polymorphisms of the μ-opioid receptor gene influence cerebral pain processing in fibromyalgia.

BackgroundDysregulation of the μ‐opioid receptor has been reported in fibromyalgia (FM) and was linked to pain severity. Here, we investigated the effect of the functional genetic polymorphism of the μ‐opioid receptor gene (OPRM1) (rs1799971) on symptom severity, pain sensitivity and cerebral pain processing in FM subjects and healthy controls (HC).MethodsSymptom severity and pressure pain sensitivity was assessed in FM subjects (n = 70) and HC (n = 35). Cerebral pain‐related activation was assessed by functional magnetic resonance imaging during individually calibrated painful pressure stimuli.ResultsFibromyalgia subjects were more pain sensitive but no significant differences in pain sensitivity or pain ratings were observed between OPRM1 genotypes. A significant difference was found in cerebral pain processing, with carriers of at least one G‐allele showing increased activation in posterior cingulate cortex (PCC) extending to precentral gyrus, compared to AA homozygotes. This effect was significant in FM subjects but not in healthy participants, however, between‐group comparisons did not yield significant results. Seed‐based functional connectivity analysis was performed with the seed based on differences in PCC/precentral gyrus activation between OPRM1 genotypes during evoked pain across groups. G‐allele carriers displayed decreased functional connectivity between PCC/precentral gyrus and prefrontal cortex.ConclusionsG‐allele carriers showed increased activation in PCC/precentral gyrus but decreased functional connectivity with the frontal control network during pressure stimulation, suggesting different pain modulatory processes between OPRM1 genotypes involving altered fronto‐parietal network involvement. Furthermore, our results suggest that the overall effects of the OPRM1 G‐allele may be driven by FM subjects.SignificanceWe show that the functional polymorphism of the μ‐opioid receptor gene OPRM1 was associated with alterations in the fronto‐parietal network as well as with increased activation of posterior cingulum during evoked pain in FM. Thus, the OPRM1 polymorphism affects cerebral processing in brain regions implicated in salience, attention, and the default mode network. This finding is discussed in the light of pain and the opioid system, providing further evidence for a functional role of OPRM1 in cerebral pain processing.

Masterclass: A pragmatic approach to pain sensitivity in people with musculoskeletal disorders and implications for clinical management for musculoskeletal clinicians

IntroductionResearch on musculoskeletal disorders indicates that pain sensitivity can be an important consideration for musculoskeletal clinicians in the holistic view of a patient presentation. However, diversity in research findings in this field can make this a difficult concept for clinicians to navigate. Limited integration of the concept of pain sensitivity into clinical practice for musculoskeletal clinicians has been noted. PurposeThe purpose of this masterclass is to provide a framework for the consideration of pain sensitivity as a contributing factor in the presentation of people with musculoskeletal pain. It provides pragmatic synthesis of the literature related to pain sensitivity through a lens of how this information can inform clinical practice for musculoskeletal clinicians. Guidance is provided in a ‘how to’ format for integration of this knowledge into the clinical encounter to facilitate personalised care. ImplicationsThe relationship of pain sensitivity with pain and disability is not clear or linear. The real importance of pain sensitivity in a clinical presentation may be: (1) the potential for pain sensitivity to modify the effect of common treatments utilised by musculoskeletal clinicians, or (2) the effect of pain sensitivity on the prognosis/course of a disorder. Screening tools and subjective features have been highlighted to indicate when physical assessment of pain sensitivity should be prioritised in the physical examination. A pragmatic blueprint for specific assessment related to pain sensitivity has been outlined. A framework for integrating assessment findings into clinical reasoning to formulate management plans for the pain sensitive patient is provided.

Sensorimotor Peak Alpha Frequency Is a Reliable Biomarker of Prolonged Pain Sensitivity.

Previous research has observed that the speed of alpha band oscillations (8-12Hz range) recorded during resting electroencephalography is slowed in chronic pain patients. While this slowing may reflect pathological changes that occur during the chronification of pain, an alternative explanation is that healthy individuals with slower alpha oscillations are more sensitive to prolonged pain, and by extension, more susceptible to developing chronic pain. To test this hypothesis, we examined the relationship between the pain-free, resting alpha oscillation speed of healthy individuals and their sensitivity to two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two visits separated by 8weeks on average (n = 61 Visit 1, n = 46 Visit 2). We observed that the speed of an individual's pain-free alpha oscillations was negatively correlated with sensitivity to both models and that this relationship was reliable across short (minutes) and long (weeks) timescales. Furthermore, the speed of pain-free alpha oscillations can successfully identify the most pain sensitive individuals, which we validated on data from a separate, independent study. These results suggest that alpha oscillation speed is a reliable biomarker of prolonged pain sensitivity with potential for prospectively identifying pain sensitivity in the clinic.

(252) The Role of Self-Other Comparisons in Race Differences in Pain Tolerance

Research has found race differences in pain sensitivity and tolerance. Evidence suggests how people compare themselves to similar others influences interpretations of their own health and well-being. We examined participants’ perceptions of their pain sensitivity compared to their perceptions of the pain sensitivity of “typical” members of their race (self-other comparison) and how these self-other comparisons related to race differences in actual pain tolerance. Black and White undergraduates (N=132; 48.5% Black) completed the Race/Ethnicity Expectations of Pain Questionnaire and a cold pressor task. First, we examined participants’ beliefs related to race differences in pain using a paired samples t-test to understand the perceived pain sensitivity of the comparison groups. Then, we examined how participants’ self-other comparison ratings for pain moderated the relationship between race and actual pain tolerance using a robust multiple-group moderation analysis. Results indicated participants rated the “typical” Black person as less pain sensitive than the “typical” White person (t(131)=-6.83, p

Pain and structural alterations in knee joints in patients with haemophilia.

Patients with haemophilia (PwH) suffer from haemophilic arthropathy which leads to an enhanced pain sensitivity. The aim of this study was to determine whether the individual pain condition in terms of pressure pain thresholds (PPT) at the knee joints is linked to changes of underlying anatomical structures in PwH. Eleven landmarks at both knee joints of 36 PwH and 36 controls were examined in terms of PPT and ultrasound sonography (US). PPT were used to generate four groups: pain sensitive and insensitive knees of PwH and controls. PPT of the knee joints were significantly decreased at all landmarks in PwH when compared to controls (P≤.004). US findings revealed that especially osteophytes are more pronounced in pain-sensitive knees of PwH in comparison with pain-insensitive knees of PwH or pain-(in)sensitive knees of controls. The synovia tissue was also thickened in PwH when PPT was altered. In contrast to findings in osteoarthritis-related pain, no differences between the groups were found regarding effusion, whether assessed, for example on the distal edge of m. vastus lateralis (P=.893) or on the lateral joint space (P=.417). Particular degenerative changes in terms of osteophytes and thickness of synovial tissue are associated with an enhanced pain sensitivity in PwH. Altered PPT which were not associated with structural findings may be an indicator for a complex peripheral and/or central sensitization of the affected joints in PwH. The role of this mechanism should be clarified in further studies.

Pain sensitivity and analgesic use among 10,486 adults: the Troms\xf8 study

BackgroundIncreased pain sensitivity is a putative risk factor for chronic pain and consequently for analgesic use. Conversely, analgesic use may be a cause of increased pain sensitivity, e.g., through opioid-induced hyperalgesia. We aimed to study the association between pain sensitivity and analgesic use in a general population, and to test the hypothesis that increased baseline pain sensitivity is a risk factor for future persistent analgesic use.MethodsThe Tromsø Study (2007–08), a population-based health study, was linked with eight years of prescription data from the Norwegian Prescription Database. The cold pressor test was completed in 10,486 participants aged 30+ years, and we used cold pressor endurance time as a proxy measure of pain sensitivity. Cross-sectional associations with different measures of analgesic use were assessed. Furthermore, a cohort of 9,657 persons was followed for 4.5 years.ResultsIn the cross-sectional analysis, increased pain sensitivity was associated with analgesic use; regular users of opioids alone were more pain sensitive than regular users of non-opioid analgesics. Increased baseline pain sensitivity was a risk factor for persistent analgesic use, i.e., using non-steroidal anti-inflammatory drugs, paracetamol, or opioids for ≥ 90 days and proportion-of-days-covered ≥ 40% (HR = 1.22, 95% CI 1.06-1.40), although not statistical significant after confounder adjustment.ConclusionsIncreased pain sensitivity was associated with analgesic use in general, and reduced pain tolerance was found for both opioid and non-opioid analgesic users. The data suggest that hyperalgesia is an effect of analgesics, whereas pain tolerance has little impact on future analgesic use.

A comparison of race-related pain stereotypes held by White and Black individuals.

Pain judgments are the basis for pain management. The purpose of this study was to assess Black and White participants' race-related pain stereotypes. Undergraduates (n=551) rated the pain sensitivity and willingness to report pain for the typical Black person, White person, and themselves. Participants, regardless of race, rated the typical White person as being more pain sensitive and more willing to report pain than the typical Black person. White participants rated themselves as less sensitive and less willing to report pain than same-race peers; however, Black participants rated themselves as more pain sensitive and more willing to report pain than same-race peers. These findings highlight similarities and differences in racial stereotypic pain beliefs held by Black and White individuals.

Pressure Pain Sensitivity Maps of the Neck-Shoulder Region in Breast Cancer Survivors.

The aim of the present study was to report pressure pain sensitivity topographical maps of the frontal and dorsal parts of the shoulder region, and locate the pressure pain sensitive areas in breast cancer survivors compared with matched healthy control subjects. Twenty-two breast cancer survivors (BCS) and 22 matched control subjects participated. A numeric pain rating scale of the neck-shoulder area and pressure pain thresholds (PPTs) was assessed bilaterally over 28 points in the frontal and dorsal neck-shoulder area. Topographical pain sensitivity maps of the upper trapezius, pectoral, and anterior deltoid areas were computed. A three-way analysis of variance was carried out to evaluate the differences in PPTs. The BCS reported spontaneous neck pain (mean ± SD 3.6 ± 2.8), pain in the affected shoulder (4.3 ± 2.7), and pain in the non-affected shoulder (0.9 ± 1.8). Additionally, the BCS exhibited bilaterally lower PPTs in all the measurement points as compared with the control subjects (P < 0.05). The PPTs were lower at the superior part of the trapezius muscle (P < 0.001), the musculotendinous insertion, the anterior part of the deltoid muscle (P < 0.001), and the tendon of the pectoral muscle (P < 0.001) as compared with the control subjects. The results suggest the sensitization processes in the BCS and give preliminary evidence to most sensitive areas in the superior part of the upper trapezius and musculotendinous insertion of the pectoral muscle.

Active pain coping is associated with the response in real-time fMRI neurofeedback during pain

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback is used as a tool to gain voluntary control of activity in various brain regions. Little emphasis has been put on the influence of cognitive and personality traits on neurofeedback efficacy and baseline activity. Here, we assessed the effect of individual pain coping on rt-fMRI neurofeedback during heat-induced pain. Twenty-eight healthy subjects completed the Coping Strategies Questionnaire (CSQ) prior to scanning. The first part of the fMRI experiment identified target regions using painful heat stimulation. Then, subjects were asked to down-regulate the pain target brain region during four neurofeedback runs with painful heat stimulation. Functional MRI analysis included correlation analysis between fMRI activation and pain ratings as well as CSQ ratings. At the behavioral level, the active pain coping (first principal component of CSQ) was correlated with pain ratings during neurofeedback. Concerning neuroimaging, pain sensitive regions were negatively correlated with pain coping. During neurofeedback, the pain coping was positively correlated with activation in the anterior cingulate cortex, prefrontal cortex, hippocampus and visual cortex. Thermode temperature was negatively correlated with anterior insula and dorsolateral prefrontal cortex activation. In conclusion, self-reported pain coping mechanisms and pain sensitivity are a source of variance during rt-fMRI neurofeedback possibly explaining variations in regulation success. In particular, active coping seems to be associated with successful pain regulation.

Why sickness hurts: A central mechanism for pain induced by peripheral inflammation

Low-grade systemic inflammation has been implicated in chronic pain, as well as in comorbid diseases like depression and fatigue. We have previously shown that women’s pain perception and regulation is more affected by systemic inflammation than that of men. Here we investigated the neural substrates underlying these effects using an fMRI paradigm previously employed in a clinical population. Fifty-one participants (29 women) were injected with 0.6ng/kg lipopolysaccharide (LPS) or saline to induce a peripheral inflammatory response. The subjects were then tested with a pressure pain fMRI paradigm designed to capture descending pain inhibitory activity 2h after injection, and blood was sampled for cytokine analysis.The subjects injected with LPS became more pain sensitive compared to the placebo group, and the heightened pain sensitivity was paralleled by decreased activity in the ventrolateral prefrontal cortex and the rostral anterior cingulate cortex (rACC) compared to placebo; areas involved in descending pain regulation. The LPS group also had higher activity in the anterior insular cortex, an area underpinning affective and interoceptive pain processing. Women displayed overall less pain-evoked rACC activity compared to men, which may have rendered women less resilient to immune provocation, possibly explaining sex differences in LPS-induced pain sensitivity. Our findings elucidate the pain-related brain circuits affected by experimental peripheral inflammation, strengthening the theoretical link between systemic inflammation and weakened pain regulation in chronic pain disorders. The results further suggest a possible mechanism underlying the female predominance in many chronic pain disorders.

Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition.

It has been suggested that increased pain sensitivity and disruption of endogenous pain inhibitory processes may account, at least in part, for the greater prevalence and severity of chronic pain in women compared to men. However, previous studies addressing this topic have produced mixed findings. This study examined sex differences in pain sensitivity and inhibition using quantitative sensory testing (QST), while also considering the influence of other important factors such as depressive symptoms and sleep quality. Healthy men (n=24) and women (n=24) each completed a QST battery. This battery included an ischemic pain task (IPT) that used a submaximal effort tourniquet procedure as well as a conditioned pain modulation (CPM) procedure for the assessment of endogenous pain inhibition. Prior to QST, participants completed the Center for Epidemiologic Studies Depression Scale and the Pittsburgh Sleep Quality Index. Analyses revealed significant sex differences for the ischemic pain task and the conditioned pain modulation procedure, such that women tolerated the ischemic pain for a shorter amount of time and demonstrated less pain inhibition compared with men. This remained true even when accounting for sex differences in depressive symptoms and sleep quality. The results of this study suggest that women may be more pain sensitive and possess less-efficient endogenous pain inhibitory capacity compared with men. Whether interventions that decrease pain sensitivity and enhance pain inhibition in women ultimately improve their clinical pain outcomes is an area of research that deserves additional attention in the future.

The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli

Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified “pain genes”. Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT), as its substantial association to pain sensitivity has been reported in various studies, but rejected in several others. In line with findings from behavioral studies, we hypothesized that the effect of COMT on pain processing would become apparent only when the pain system was adequately challenged (i.e., after repeated pain stimulation). In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12). Met/met subjects exhibited stronger pain-related fMRI signals than val/val in several brain structures, including the periaqueductal gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus. These effects were observed only for high intensity pain stimuli after repeated administration. In spite of our relatively small sample size, our results suggest that COMT appears to affect pain processing. Our data demonstrate that the effect of COMT on pain processing can be detected in presence of 1) a sufficiently robust challenge to the pain system to detect a genotype effect, and/or 2) the recruitment of pain-dampening compensatory mechanisms by the putatively more pain sensitive met homozygotes. These findings may help explain the inconsistencies in reported findings of the impact of COMT in pain regulation.

1001 Psychological Distress is a Major Risk Factor for the Continuation of Functional Gastrointestinal Disorders (FGIDs) 12 Years Later in the General Population

Background and aims: Visceral pain sensitivity is influenced by psychological bias in perception reflected in the sensory decision theory index “B”. We sought to develop a noninvasive questionnaire to identify patients with visceral hyperalgesia by identifying questions correlated with the B index.Methods: 107 Rome III positive, clinically diagnosed IBS patients completed a barostat test of rectal pain sensitivity and the following questionnaires: Clinical symptoms of pain and bloating, Recent Physical Symptoms Questionnaire (RPSQ) somatization scale, Pennebaker Inventory of Limbic Languidness (PILL), Pain Vigilance and Awareness Questionnaire (PVAQ), Somatosensory Amplification Scale (SAS), Tellegen Absorption Scale, Visceral Sensitivity Index, and Dissociation, Anxiety, Depression, Sexual Abuse Trauma Index, and Sleep Disturbance subscales of the Trauma Symptoms Checklist 40. The B index and corrected pain threshold (subtracted pressure required to minimally inflate bag) were computed from barostat data. As planned a priori, we also pooled all 218 questions from all scales and used t-tests to identify items which separated the lowest from the highest third of B Index scores. The 26 non-redundant items so identified formed the Visceral Perception Bias Questionnaire (VPBQ), which was scored by summing individual items. Results: The sample was 79% females with average age of 37.2 years. The mean and range for the IOP-adjusted pain threshold was 15.9 (0-44) mmHg and for the B Index 3.3 (0.9-5.5). Clinical pain was not significantly correlated with the B Index or pain threshold, but bloating severity was correlated with pain threshold (-0.22, p<0.05). Conventionally computed scores for some questionnaires (RPSQ, Tellegen Absorption Scale, Dissociation scale, anxiety, depression, and sexual abuse) were significantly correlated with the B Index and pain threshold (PVAQ, Dissociation Scale); however, no correlation exceeded 0.27, which was not strong enough to permit identification of patients with low pain thresholds. The empirically derived VPBQ performed better: it correlated -0.31 with pain threshold and -0.48 with the B Index. A VPBQ score of 35 or higher (67th percentile) identified 51.5% of patients with pain thresholds below 12 mmHg and 64.5% of patients with B Index scores below 2.71 (most sensitive third of patients). Conclusion: The empirically derived VPBQ identified more than half of the most pain sensitive IBS patients, indicating that this is a promising approach. However, further refinement and testing in a new sample of subjects including healthy controls is needed. [Supported by a grant from Takeda Pharmaceuticals and R24 DK067674]

Comparison of pain and dyspnea perceptual responses in healthy subjects

Dyspnea and pain have a number of similarities. Recent brain imaging experiments showed that similar cortical regions are activated by the perceptions of dyspnea and pain. We tested the hypothesis that an individual’s pain sensitivity might parallel the individual’s dyspnea sensitivity. Studies were carried out in 52 young healthy subjects. Each subject experienced experimentally induced pain and dyspnea. Pain was induced by a cold-pressor test and dyspnea was induced by breathholding while the unpleasant experience of pain and dyspnea was assessed by using a Visual Analogue Scale (VAS). The times from the start of cold stimulation and breathholding to the onset of uncomfortable sensation (pain threshold time and the period of no respiratory sensation, respectively) and to the limit of tolerance (pain endurance time and total breathholding time, respectively) were also measured. In response to cold pain stimulation, a behavioral dichotomy (pain-tolerant and pain-sensitive) was observed. The period of no respiratory sensation was significantly shorter in the PS (pain-sensitive) group than in the PT (pain-tolerant) group (16.9±3.8 vs. 19.6±5.3 s: P<0.05), whereas no significant difference in the total breathholding time was found between the PT and PS groups. A significant correlation was observed between the pain threshold time and the period of no respiratory sensation in both the PT and PS groups. However, no significant association was observed between pain and dyspnea tolerance in both groups. In conclusion, an individual’s pain threshold is correlated to the individual’s dyspnea threshold, but the individual’s pain tolerance is not consistently correlated to the individual’s dyspnea tolerance.

Women experience greater heat pain adaptation and habituation than men

It is not clear how males and females cope with pain over time and how sensory and emotional qualities fluctuate from moment to moment, although studies of pain at discrete time points suggest that women are more pain sensitive than men. Therefore, we developed a new broader-based pain model that incorporates a temporally continuous assessment of multiple pain dimensions across sensory and affective dimensions, and normalized peak pain intensity to unmask sex differences that may otherwise be confounded by inter-individual variability in pain sensitivity. We obtained continuous ratings of pain, burning, sharp, stinging, cutting, and annoyance evoked by repeated prolonged noxious heat stimuli in 32 subjects. Strikingly, females reported more pain than males at the outset of the first exposure to pain, but then experienced less pain and annoyance than males as a painful stimulus was sustained and with repeated stimulation. Patterns of pain and annoyance attenuation in women resembled the attenuation of sharp, stinging and cutting sensations, whereas patterns of pain and annoyance in men resembled burning sensations. Taken together, these data demonstrate a prominent sex difference in the time course of pain. Notably only females demonstrate adaptation and habituation that allow them to experience less pain over time. These findings suggest a sexual dichotomy in mechanisms underlying pain intensity and annoyance that could involve specific quality-linked mechanisms. Importantly, temporal processing of pain differs between males and females when adjusted for sex differences in pain sensitivity. Our findings provide insight into sex differences in tonic and possibly chronic pains.