Experimental Pain Sensitivity Research Articles

(494) Optimizing resilience in orofacial pain and nociception (ORION): exploring the efficacy of a hope intervention for pain

Resilience is a dynamic process resulting in positive adjustment and adaptation after exposure to adversity. In recent years, there has been growing interest in the contribution of positive psychological factors to pain and pain-related coping; however, interventions built upon bolstering resilience have received less attention. Hope is a strength-based motivational state consisting of one’s belief in their ability to generate routes to achieve goals (pathways) and initiating directional activity towards attaining goals (agency). Emerging evidence supports the role of hope in psychosocial adjustment and adaptive pain coping, suggesting that approaches designed to foster hope and personal strengths may enhance pain adaptation. Therefore, the overall objective of this pilot study was to test the feasibility and efficacy of a resilience-oriented hope intervention for clinical pain, as well as psychosocial outcomes and experimental pain sensitivity in individuals with orofacial pain. Twenty-three participants (78% female) with temporomandibular disorder were randomized to a 3-session intervention intended to increase hope or a control intervention involving education about pain and stress. Prior to and after the intervention, participants attended two laboratory sessions whereby they completed psychosocial questionnaires and sensitivity to heat, cold, and pressure pain was assessed. Hope was measured by the Adult State Hope Scale. Results indicated that higher levels of hope were associated with greater pressure pain thresholds at all sites: temporalis, masseter, temporomandibular joint [TMJ], forearm, trapezius, tibialis anterior (r’s=.31-.49; p’s<.03). Compared to Pain Education, the Hope group exhibited an increase in hope, reductions in pain catastrophizing, as well as greater increases in heat pain tolerance and pressure pain thresholds at the tibialis anterior and TMJ. Although preliminary, these results suggest that resilience-oriented interventions may be beneficial in reducing pain and catastrophizing and could serve as a target for pain management. Funded by the APS Sharon S. Keller Chronic Pain Research grant.

(209) Association of socioeconomic factors with pain and function in older adults with knee osteoarthritis

The pain and loss of function evoked by knee osteoarthritis (OA) contribute significantly to decreased quality of life in older adults. A robust inverse association between socio-economic status (SES) and negative health outcomes has been well documented. The present analysis seeks to investigate potential associations between SES indicators and clinical and experimental pain measures in older adults with knee OA. Older adults with knee OA (n=292) underwent a battery of clinical and experimental pain assessments over several sessions. Participants reported demographic, clinical pain and SES information including annual household income and education level. Individuals also underwent the Short Physical Performance Battery (SPPB) to assess physical function. Participants reporting an annual household income of <$40,000 reported greater levels of pain (p>0.01), impairment (p<0.01), and stiffness (p<0.05) on the WOMAC compared to those with >$40,000. They also reported greater levels of pain during the SPPB balance and walking tasks (p<0.01). Similarly, participants with no university education reported greater levels of knee pain (p<0.01), impairment (p<0.01), and stiffness (p<0.05) on the WOMAC. These associations remained significant even after accounting for age, race, sex, and body mass index. Similar associations emerged for mechanical and thermal experimental pain measures, where lower SES was associated with increased experimental pain sensitivity (p<0.05). Our findings suggest that education and income levels are both inversely associated with greater levels of clinical knee pain and physical performance in older adults with knee OA. Further research is needed to more comprehensively understand the interaction between SES and clinical pain in individuals with knee OA.

Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity.

Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). Heat detection and heat pain thresholds at clinical painful and nonpainful body areas were assessed. Based on TSP and CPM, 4 distinct groups were formed: group 1 (n = 85) had impaired CPM and facilitated TSP; group 2 (n = 148) had impaired CPM and normal TSP; group 3 (n = 45) had normal CPM and facilitated TSP; and group 4 (n = 122) had normal CPM and normal TSP. Group 1 showed more pain regions than the other 3 groups (P < 0.001), indicating that impaired CPM and facilitated TSP play an important role in widespread pain. Groups 1 and 2 compared with group 4 had lower heat pain threshold at nonpainful areas and lower cuff pressure pain tolerance (P < 0.02), indicating that CPM plays a role for widespread hyperalgesia. Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.

Experimental pain sensitivity in multiple system atrophy and Parkinson's disease at an early stage.

Chronic spontaneous pain is a clinically relevant non-motor symptom in multiple system atrophy (MSA) and Parkinson's disease (PD). Experimental pain sensitivity, reflecting the mechanisms of nociception and pain perception leading to clinical pain, is known to be enhanced in both diseases at advanced stages. Also, this study aimed at investigating experimental pain sensitivity already at an early stage (i.e. symptom duration ≤5years). Experimental pain sensitivity was assessed by investigating the nociceptive flexion reflex (NFR, reflecting spinal nociception) and heat and electrical pain thresholds. 'Off-drug' MSA (n=11) and PD (n=14) patients selected at an early stage of the disease were compared to healthy controls (HC, n=27). MSA patients had either parkinsonian (MSA-P, n=5) or cerebellar (MSA-C, n=6) subtypes. Compared to HC, MSA patients had lower heat pain sensitivity, whereas PD patients had reduced NFR threshold. MSA and PD patients did not differ from HC regarding other variables. MSA-P and MSA-C patients did not differ, either. Impaired sensory discrimination and attention deficits could contribute to the reduced perception of heat pain in MSA, whereas in PD, local changes in spinal excitability or a diminished dopaminergic descending inhibition might impact on the motor efference of the NFR to reduce its threshold to nociceptive afferent information. WHAT DOES THIS STUDY ADD?: This study investigated experimental pain sensitivity at an early stage in MSA and PD.

Hormonal contraceptive pill effect on pain sensitivity response

Background and Aim: Estrogen strongly influences nociceptive actions, whereas progesterone prevents the neuropathic pain. However, there is only a little evidence on the direct effect of hormonal-based drugs on the experimental pain sensitivity response. Therefore, the aim of the present study was to investigate the effect of hormonal combined oral contraceptive pill (COCP) on pain sensitivity. Methods: A total of 45 participants (15 men [control], 15 women [using COCP], and 15 women menstruating naturally) were subjected to cold pressor test. Participants relaxed their least dominant arm in a 32΀C water bath (3 min) and then the hand was plunged into an ice slurry bath (0΀C-2΀C). The time taken for the participant to report the pain was recorded as pain threshold. The time from pain threshold to the participant no longer able to tolerate the pain was recorded as pain tolerance. Pain intensity and pain unpleasantness were recorded using the visual analog scale. Results: The pain tolerance was significantly greater ( P = 0.02) in women using COCP compared to control women (women not on COCP) and men. The pain unpleasantness was significantly decreased ( P = 0.04) in COCP women compared to control women (women not on COCP) and men. Conclusion: Women using COCP have more tolerance and less unpleasantness to the pain threshold. They appear to respond differently than women menstruating naturally to cold pressor pain, which may be due to psychological, social, or environmental factors that need to be evaluated in future studies.

Impact of Psychological Covariates on Experimental Pain Sensitivity in Children and Adolescents with SCD

Background: Children with Sickle Cell Disease (SCD) have increased sensitivity to heat and cold pain (Brandow et al) during steady state. However, the role of psychological factors such as anxiety, depressive symptoms and catastrophizing on pain sensitivity is not known in SCD. Characterization of these factors may provide an insight into the study of their possible roles in the transition to chronic pain.Aim: To determine if psychological factors impact pain sensitivity in patients with SCD.Methods: Patients with SCD were offered quantitative sensory testing (QST) when at steady state (at least 2 weeks following a VOE). QST procedures included estimation of pressure, mechanical and thermal pain thresholds (minimum intensity of stimulus which is first perceived as painful) and tolerances (maximum intensity of a pain-producing stimulus that a participant is willing to accept in a given situation) as well as windup values (increased pain perception to repetitive painful stimuli). At each time point, participants completed the PROMIS measures of pain intensity, pain interference, anxiety, depressive symptoms, sleep, fatigue and peer relationships. Participants also completed the Pain Catastrophizing Scale ((PCS)-Sullivan et al), Child Somatization Inventory (Walker et al), Pain Coping Inventory (Varni et al)* as well as Peds QL Generic and SCD specific measures of Quality of life*.Results: We determined the experimental pain phenotype (sensitivity to pressure, mechanical and thermal pain) of 29 patients with SCD during steady state (> 2 weeks from a vaso-occlusive episode). These participants were not receiving long-term opioids or adjunctive medications for pain. The median age of participants was 15 (IQR 10-19) and majority (69%) were female. Approximately half of the study sample had HbSS. Three quarters of the study sample were prescribed hydroxyurea. The median Hb level was 11.1 (IQR 10.2-11.6). The median number of VOC's in the year prior to testing was 1(IQR 0-2) and in 3 years prior to testing was 3 (IQR 2-5). The median PROMIS pain intensity T-score was 37.8, PROMIS pain interference T-score was 48.75, PROMIS Depressive symptom T-score was 44.35 and PROMIS anxiety was 43.9; these scores were not higher than the average T-score of 50 described in the pediatric population. High catastrophizing scores were reported on the PCS, with median score being 29. The median cold pain threshold was 23.6 degrees C (IQR 15.8-26.7) and median heat pain threshold was 39.1 degrees C (IQR 37.5-40.9).We noted that increase in scores on PROMIS depressive symptoms was associated with lower heat (Spearman's rho= -0.55), cold (Spearman's rho= 0.57) and mechanical (Spearman's rho= -0.4) pain thresholds. Scores on PROMIS depressive symptoms predicted heat and cold pain thresholds independent of age and VOC's in the past 3 years. Increased PROMIS anxiety scores were associated with lower mechanical pain thresholds (Spearman's rho= -0.43) and lower cold detection thresholds (Spearman's rho= 0.46). Increased scores on PCS were associated with lower heat detection thresholds (Spearman's' rho= -0.39). (All p-values were<0.05) Table 1OutcomeDepressive symptomsVOCs in 3 years prior to studyAge (years)Model signCoeffp-valueCoeffp-valueCoeffp-valueCold Pain Threshold0.40.003-0.190.6-0.410.16<0.0127Heat Pain Threshold-0.120.0130.380.0120.20.068<0.00128Conclusions: Depressive symptoms and anxiety are associated with lower experimental pain thresholds in patients with SCD. Higher scores on PROMIS depressive symptoms predict increased sensitivity to heat and cold pain independent of age and number of VOCs experienced in the past 3 years. Further studies are needed to determine the contribution of psychological factors in the transition to chronic pain in SCD.Acknowledgments: 1-Sickle Cell Disease Association of America 2- *PedsQL™ contact information and permission to use: Mapi Research Trust, Lyon, France. E-mail: PROinformation@mapi-trust.org - Internet: www.Mapi-trust.org and http://www.pedsql.org/index.html DisclosuresNo relevant conflicts of interest to declare.

Differential dopamine function in fibromyalgia.

Approximately 30% of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [(18)F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and 11 female controls completed study procedures. Subjects received one FAL PET scan while performing a "2-back" task, and one while performing a "0-back" (attentional control, "baseline") task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.

Hepatitis C virus infection and pain sensitivity in patients on methadone or buprenorphine maintenance therapy for opioid use disorders

BackgroundPatients with opioid use disorders on opioid agonist therapy (OAT) have lower pain tolerance compared to controls. While chronic viral infections such as HCV and HIV have been associated with chronic pain in this population, no studies have examined their impact on pain sensitivity. MethodsWe recruited 106 adults (41 uninfected controls; 40 HCV mono-infected; and 25 HCV/HIV co-infected) on buprenorphine or methadone to assess whether HCV infection (with or without HIV) was associated with increased experimental pain sensitivity and self-reported pain. The primary outcome was cold pain tolerance assessed by cold-pressor test. Secondary outcomes were cold pain thresholds, wind-up ratios to repetitive mechanical stimulation (i.e., temporal summation) and acute and chronic pain. Multivariable regression models evaluated associations between viral infection status and outcomes, adjusting for other factors. ResultsNo significant differences were detected across groups for primary or secondary outcomes. Adjusted mean cold pain tolerance was 25.7 (uninfected controls) vs. 26.8 (HCV mono-infection) vs. 25.3 (HCV/HIV co-infection) seconds (global p-value=0.93). Current pain appeared more prevalent among HCV mono-infected (93%) compared to HCV/HIV co-infected participants (76%) and uninfected controls (80%), as did chronic pain (77% vs. 64% vs. 61%, respectively). However, differences were not statistically significant in multivariable models. ConclusionThis study did not detect an association between HCV infection and increased sensitivity to pain among adults with and without HIV who were treated with buprenorphine or methadone for opioid use disorders. Results reinforce that pain and hyperalgesia are common problems in this population.

Does pain vary across the menstrual cycle? A review.

Reproductive hormones are implicated in moderating pain. Animal studies support both pronociceptive and antinociceptive actions of oestradiol and progesterone suggesting that the net effect of these hormones on pain is complex and likely depends on the interaction between hormones and the extent of fluctuation rather than absolute hormone levels. Several clinical pain conditions show variation in symptom severity across the menstrual cycle. Though, there is still no consensus on whether the menstrual cycle influences experimental pain sensitivity in healthy individuals. Comprehensive literature searches on clinical and experimental pain across the menstrual cycle, as well as gonadal hormones and pain were performed using the electronic databases PubMed, Google Scholar and the Cochrane Library. Full-text manuscripts were reviewed for relevancy and reference lists were cross-checked for additional relevant studies. Most of the more recent, well-controlled studies show that menstrual cycle phase has no effect on the perception of pain in healthy, pain-free women. Although recent studies investigating pain-related brain activation have shown differential activation patterns across the menstrual cycle in regions involved with cognitive and motor function, even in the absence of a behavioural pain response, suggesting that cognitive pain and bodily awareness systems are sensitive to menstrual cycle phase. The interaction between the gonadal hormones and pain perception is intricate and not entirely understood. We suggest further investigations on the association between female reproductive hormones and pain sensitivity by exploring the interaction between clinical and experimental pain and the hormone changes that characterize puberty, post-partum and the menopause transition.

(222) Experimental pain sensitivity and clinical pain severity in Asian Americans compared to non-Hispanic whites with knee osteoarthritis

(222) Experimental pain sensitivity and clinical pain severity in Asian Americans compared to non-Hispanic whites with knee osteoarthritis

(298) Stoicism is associated with experimental measures of pain perception, but not spinal nociception

Evidence suggests that stoic attitudes may be related to the experience of pain. The present study examined the relationship between pain-related stoicism and experimental pain sensitivity in 25 healthy, pain-free men and women. Pain sensitivity was assessed over two testing sessions from electrocutaneous pain threshold/tolerance, heat pain threshold/tolerance, ischemic pain threshold/tolerance, cold pain threshold/tolerance, and nociceptive flexion reflex (NFR) threshold (a physiological measure of spinal nociception).

In Vivo Praying and Catastrophizing Mediate the Race Differences in Experimental Pain Sensitivity

Black individuals have a lower tolerance for experimental pain than white individuals. Black and white individuals also differ in their use of pain coping strategies, which may explain the race differences in pain sensitivity. We examined the extent to which situation-specific pain coping mediated black-white differences in pain sensitivity. We hypothesized that 1) black participants would demonstrate lower pain tolerance than white participants, 2) black participants would use different pain coping strategies than white participants, and 3) the differential use of these strategies would mediate the relationship between race and pain tolerance. Healthy college undergraduates (N = 190) participated in a cold pressor task and then completed the Coping Strategies Questionnaire–Revised to assess their situation-specific pain coping. Compared with white participants, black participants demonstrated lower pain tolerance, engaged in more situation-specific catastrophizing and praying, and ignored pain less frequently. Catastrophizing and praying were inversely related to pain tolerance and were significant mediators of the relationship between race and pain tolerance. The indirect effect of praying was stronger than that of catastrophizing. Race differences in pain sensitivity may be due, in part, to differences in the use of catastrophizing and praying as coping strategies. These results may help guide treatments addressing maladaptive pain coping. PerspectiveThis study suggests that race differences in pain sensitivity may be due, in part, to the differential use of catastrophizing and praying strategies. Psychosocial treatments for pain should encourage patients to take an active role in their pain management.

Social Support Attenuates Physiological Stress Responses and Experimental Pain Sensitivity to Cold Pressor Pain.

Social support improves health and has been shown to attenuate stress and pain. The precise characteristics of social support responsible for these effects, however, remain elusive. The purpose of this study is to examine the relative efficacy of social support versus a neutral non-verbal social presence to attenuate stress and pain. Seventy-six participants provided pain ratings and task assessments during a cold pressor task (CPT) in one of three conditions: verbal social support, neutral non-support, or alone. Reactivity to the CPT was assessed via cardiovascular measures, cortisol, and subjective ratings. Participants receiving social support showed attenuated blood pressure, heart rate, and cortisol reactivity, as well as reduced pain ratings, task difficulty, tension, and effort compared to neutral non-support and alone conditions. Social support, not the mere presence of another individual, attenuated stress and pain during a CPT. Given the negative health consequences of stress and pain, clinical studies incorporating social support into medical procedures and treatments are warranted.

Negative affectivity predicts decreased pain tolerance during low-grade inflammation in healthy women.

Experimental animal studies provided evidence for a synergistic effect of immunological and psychological stressors on subsequent sickness behaviours. Up to now, little corroborating evidence for such synergy exists for humans, in whom it may provide a mechanism leading to the expression of functional somatic symptoms. The aim of the present study was to determine an interaction between stress(-vulnerability) and an immunological activation on experimental pain sensitivity, i.e., pressure pain threshold and tolerance in healthy humans. In healthy female participants (n=25, mean age 22.3 years), negative affectivity (NA) and experienced stress were assessed by questionnaire before receiving a Salmonella typhi vaccine or saline control in a randomized blinded cross-over design. Pressure pain threshold was assessed at the lower back and calves and pain tolerance was assessed at the thumbnail, before and six hours after each injection. Vaccination induced leukocytosis (+100%) and increased serum IL-6 (+670%). NA predicted decreased pain tolerance after vaccination (β=-.57, p=.007), but not after placebo (β=.25, p=.26). Post-hoc analyses also demonstrated an association with administration order. NA moderated the effects of inflammation on pain tolerance. This finding is consistent with a synergistic model whereby inflammation may lower the threshold for pain reporting in individuals with increased vulnerability for somatic symptom reporting.

164. Negative affectivity predicts decreased pain tolerance during low-grade inflammation in healthy women

Introduction: Experimental animal studies provided evidence for a synergistic effect of immunological and psychological stressors on subsequent sickness behaviors. This possibly provides a mechanism leading to the expression of functional somatic symptoms. Up to now little corroborating evidence for such synergy exists for humans in whom it may provide a mechanism leading to the expression of functional somatic symptoms. The aim of the present study was to determine an interaction between psychological stress (-vulnerability) and an immunological activator on experimental pain sensitivity in healthy humans. Methods: In healthy female participants (n = 25, mean age 22.3 years), negative affectivity (NA) and experienced stress were assessed by questionnaire before receiving a Salmonella typhi vaccine or saline control in a randomized blinded cross-over design. Pressure pain threshold was assessed at the lower back and calves and pain tolerance was assessed at the thumbnail, before and six hours after each injection. Results: Vaccination induced low-grade inflammation as shown by leukocytosis (+100%) and increased serum interleukin-6 (+670%). NA predicted decreased pain tolerance after vaccination (beta = −.57, p = .007), but not after placebo (beta = .25, p = .26). Conclusions: NA moderated the effects of inflammation on pain tolerance. This finding is consistent with a synergistic model whereby inflammation may lower the threshold for pain reporting in individuals with increased vulnerability for somatic symptom reporting.

(401) Mast cell stabilizer (ketotifen): implications for the pathophysiology of Fibromyalgia

Emerging data suggest that fibromyalgia (FM) is a neuro-immunologic disorder. Compared to healthy controls, FM patients have greater number of skin mast cells - potent inflammatory cells capable of releasing pro-inflammatory and neuro-sensitisizing molecules. Whether or not these cells are involved in the pathogenesis of FM is unclear. We designed a randomized controlled trial to determine the effects of a mast cell stabilizer (ketotifen) on FM symptoms. Ketotifen is commonly used to treat two mast cell-mediated conditions, bronchial asthma and allergic skin disorders. Fifty-one FM subjects were randomized to daily oral ketotifen 2 mg BID (n=24) for 8 weeks or placebo (N=27). Those with atopic dermatitis, chronic urticaria, or taking anti-allergy drugs were excluded. Demographics of the 51 FM subjects: mean age= 51.2 (SD 8.4) years; female=88%; whites= 88%; ≥high school graduates=71%; concomitant opiates=22%; PHQ-8 depression=13.5 (5.4); experimental pressure pain sensitivity (range 0-20) = 10.0 (0.4); weekly average pain intensity (ActiWatch Pain Monitor) = 6.4 (1.1); and revised FIQ (global FM symptom severity) =66.8 (14.0). We found no statistically significant treatment group differences in the baseline to week 8 changes of our two primary measures: weekly average pain intensity [ketotifen -1.3 (1.9) vs. placebo -1.5 (1.9), p=0.7]; and revised FIQ [-12.1 (19.5) vs. -12.2 (18.1), p=0.9]. Further, no secondary outcome measures (BPI pain intensity, and experimental pressure pain sensitivity) reached statistical significance (p>0.5). Our results did not differ in the intent-to-treat and completer analyses. Three subjects in the ketotifen group and 2 in the placebo group discontinued the study due to study protocol violations. Other than transient sedation [6 (28.6%) vs. 1 (4.0%)], oral ketotifen was well tolerated. In conclusion, oral ketotifen was not associated with improvement of FM symptoms. Importantly, skin mast cells are not major contributor in the pathogenesis of FM. Funded by NIAMS (NIH).

(355) Fatigue is associated with enhanced retrospective report of pain, but not enhanced spinal nociception, in a study of experimental pain and the menstrual cycle

Correlational and experimental evidence suggests that sleep disturbance can enhance pain. The present study examined the relationship between daytime fatigue and experimental pain sensitivity in 58 healthy, pain-free, normally-cycling women. Pain sensitivity was assessed from electrocutaneous pain threshold/tolerance, nociceptive flexion reflex (NFR) threshold (a physiological measure of spinal nociception), and retrospective reports of sensory and affective pain in response to electrocutaneous stimulations (assessed from McGill Pain Questionnaire-Short Form).

Pain Hypervigilance is Associated with Greater Clinical Pain Severity and Enhanced Experimental Pain Sensitivity Among Adults with Symptomatic Knee Osteoarthritis

Pain hypervigilance is an important aspect of the fear-avoidance model of pain that may help explain individual differences in pain sensitivity among persons with knee osteoarthritis (OA). The purpose of this study was to examine the contribution of pain hypervigilance to clinical pain severity and experimental pain sensitivity in persons with symptomatic knee OA. We analyzed cross-sectional data from 168 adults with symptomatic knee OA. Quantitative sensory testing was used to measure sensitivity to heat pain, pressure pain, and cold pain, as well as temporal summation of heat pain, a marker of central sensitization. Pain hypervigilance was associated with greater clinical pain severity, as well as greater pressure pain. Pain hypervigilance was also a significant predictor of temporal summation of heat pain. Pain hypervigilance may be an important contributor to pain reports and experimental pain sensitivity among persons with knee OA.

Multivariable Modeling of Phenotypic Risk Factors for First-Onset TMD: The OPPERA Prospective Cohort Study

Incidence of temporomandibular disorder (TMD) was predicted with multivariable models that used putative risk factors collected from initially TMD-free individuals in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. The 202 baseline risk factors included sociodemographic and clinical characteristics, measures of general health status, experimental pain sensitivity, autonomic function, and psychological distress. Study participants (n = 2,737) were then followed prospectively for a median of 2.8 years to ascertain cases of first-onset TMD. Lasso regression and random forest models were used to predict incidence of first-onset TMD using all of the aforementioned measures. Variable importance scores identified the most important risk factors, and their relationship with TMD incidence was illustrated graphically using partial dependence plots. Two of the most important risk factors for elevated TMD incidence were greater numbers of comorbid pain conditions and greater extent of nonspecific orofacial symptoms. Other important baseline risk factors were preexisting bodily pain, heightened somatic awareness, and greater extent of pain in response to examiners' palpation of the head, neck, and body. Several demographic variables persisted as risk factors even after adjusting for other OPPERA variables, suggesting that environmental variables not measured in OPPERA may also contribute to first-onset TMD. PerspectiveMultivariable methods were used to identify the most important predictors of first-onset TMD in the OPPERA study. Important variables included comorbid pain conditions, preexisting pain, and somatic awareness. Demographic characteristics, which probably reflect environmental variables not measured in OPPERA, also appear to play an important role in the etiology of TMD.

Sex Differences in How Social Networks and Relationship Quality Influence Experimental Pain Sensitivity

This is the first study to examine how both structural and functional components of individuals’ social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one’s significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual’s social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed.