Experimental Pain Sensitivity Research Articles

Experimental Pain and Auditory Sensitivity in Overactive Bladder Syndrome: A Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Study.

The objective of this study was to investigate the presence of nonbladder sensory abnormalities in participants with overactive bladder syndrome (OAB). Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study participants with OAB symptoms and controls were recruited from 6 U.S. tertiary referral centers. Quantitative sensory testing (QST) was performed to determine pressure pain sensitivity at the thumbnail bed and auditory sensitivity. Fixed and mixed effect multivariable linear regressions and Weibull models were used to compare QST responses between groups. Pearson correlations were used to assess the relationship between QST measures. Associations between QST and self-reported symptoms were explored with linear regression. A total of 297 participants were analyzed (191 OAB, 106 controls; 76% white, 51% male). OAB cases were older than controls (57.4 vs 52.2 years, p=0.015). No significant differences in experimental thumbnail (nonbladder) pain or auditory sensitivity were detected between OAB cases and controls. Correlations between pressure and auditory derived metrics were weak to moderate overall for both groups, with some significantly stronger correlations for cases. Exploratory analyses indicated increased pressure pain and auditory sensitivity were modestly associated with greater self-reported bladder pain and pain interference with physical function. As a group, no significant differences between OAB cases and controls were observed in experimental nonbladder pain or auditory sensitivity during QST. Associations between QST outcomes and clinical pain raise the possibility of centrally mediated sensory amplification in some individuals with OAB.

Pain differences in neurite orientation dispersion and density imaging measures among community-dwelling older adults

Neurite orientation dispersion and density imaging (NODDI) is a technique providing more detailed information on the microstructural bases of white matter. Given the previously reported white matter contributions to chronic pain, the present study aims to investigate pain-specific differences in NODDI measures across white matter tracts in a sample of community-dwelling older adults with (n = 29) and without (n = 18) chronic musculoskeletal pain. We further aimed to investigate associations between NODDI measures and clinical and experimental pain measures. As part of the Nepal study, a subset of older adults (>60 years old), underwent multiple laboratory sessions providing self-reported and experimental pain measures and a diffusion weighted neuroimaging sequence. Older adults with chronic musculoskeletal pain had a lower neurite density with less geometric complexity across a number of white matter tracts compared to older pain-free controls (corrected p's < 0.05). Lower neurite density was associated with greater self-reported pain intensity and anatomical pain sites, as well as greater experimental pain sensitivity (p's < 0.05). There were also significant pain-by-sex differences in neurite density and geometric complexity across multiple white matter tracts mainly around the hippocampus (corrected p's < 0.05). Finally, there were no pain differences with respect to extra-cellular water diffusion (corrected p's > 0.05). Our study demonstrates less geometric complexity in neurite density and architecture in chronic musculoskeletal pain, partly in a sex-dependent manner. An increased understanding of neurobiological mechanisms such as those measured by NODDI may contribute to the potential targeting of interventions in our older population suffering from chronic pain.

Synergistic effect of chronic pain and nonsuicidal self-harm on pain sensitivity.

Abnormalities in pain processing have been observed in patients with chronic pain conditions and in individuals who engage in self-harm, specifically nonsuicidal self-injurious behaviors (NSSI). Both increased and decreased pain sensitivity have been described in chronic pain patients, while decreased pain sensitivity is consistently observed in individuals with NSSI. The objective of the study was to identify the differential effects of chronic pain and NSSI on experimental pain sensitivity, specifically pressure pain threshold, in depressed patients. Moreover, the role that hopelessness may play between depression severity and pain sensitivity was also examined. Depressed patients with and without chronic pain, and with and without lifetime self-harm behaviors were analyzed into four groups. Group 1 (N = 42) included depressed patients with both Chronic pain ( +) and Self-harm ( +), Group 2 (N = 53) included depressed patients with Chronic pain ( +) but no Self-harm (-), Group 3 (N = 64) included depressed patients without Chronic pain (-), but Self-harm ( +), and Group 4 (N = 81) included depressed patients with neither Chronic pain (-) nor Self-harm (-). Healthy controls (N = 45) were also recruited from the community. Depressed patients with both Chronic pain ( +) and Self-harm ( +) reported higher pressure pain threshold measures when compared with the other groups. Mediation analysis indicated that hopelessness mediates the relationship between depression severity and pressure pain threshold. Our findings suggest that a multiprong approach including adequate mental health services and pain control for depressed patients with comorbid chronic pain and nonsuicidal self-harm is needed to yield effective outcomes.

Clinical, psychological, and sensory characteristics associated with headache attributed to temporomandibular disorder in people with chronic myogenous temporomandibular disorder and primary headaches

BackgroundHeadache attributed to Temporomandibular Disorder (HATMD) is a secondary headache that may have features resulting in diagnostic overlap with primary headaches, namely, tension-type (TTH) or migraine. This cross-sectional study of people with both chronic myogenous TMD and primary headaches evaluated characteristics associated with HATMD.MethodsFrom a clinical trial of adults, baseline data were used from a subset with diagnoses of both TMD myalgia according to the Diagnostic Criteria for TMD (DC/TMD) and TTH or migraine according to the International Classification of Headache Disorders, 3rd edition. HATMD was classified based on the DC/TMD. Questionnaires and examinations evaluated 42 characteristics of facial pain, headache, general health, psychological distress, and experimental pain sensitivity. Univariate regression models quantified the associations of each characteristic with HATMD (present versus absent), headache type (TTH versus migraine), and their interaction in a factorial design. Multivariable lasso regression identified the most important predictors of HATMD.ResultsOf 185 participants, 114 (61.6%) had HATMD, while the numbers with TTH (n = 98, 53.0%) and migraine (n = 87, 47.0%) were similar. HATMD was more likely among migraineurs (61/87 = 70.1%) than participants with TTH (53/98 = 54.1%; odds ratio = 2.0; 95%CL = 1.1, 3.7). In univariate analyses, characteristics associated with HATMD included pain-free jaw opening and examination-evoked pain in masticatory muscles and temporomandibular joints (TMJ) as well as frequency and impact of headache, but not frequency or impact of facial pain. Lowered blood pressure but not psychological or sensory characteristics was associated with HATMD. Multiple characteristics of facial pain, headache, general health, and psychological distress differed between TTH or migraine groups. Few interactions were observed, demonstrating that most characteristics’ associations with HATMD were consistent in TTH and migraine groups. The lasso model identified headache frequency and examination-evoked muscle pain as the most important predictors of HATMD.ConclusionsHATMD is highly prevalent among patients with chronic myogenous TMD and headaches and often presents as migraine. In contrast to primary headaches, HATMD is associated with higher headache frequency and examination-evoked masticatory muscle pain, but with surprisingly few measures of facial pain, general health, and psychological distress. A better understanding of HATMD is necessary for developing targeted strategies for its management.Trial identification and registrationSOPPRANO; NCT02437383. Registered May 7, 2015.

Sex differences in Brain Structure in individuals with knee osteoarthritis pain.

There is evidence of sex differences in the prevalence of chronic musculoskeletal pain as well as in experimental pain sensitivity. However, the neurobiological mechanisms contributing to these sex differences are poorly understood, especially with respect to brain structure. The aim of the present study is to examine sex differences in brain structure in persons with knee osteoarthritis (KOA) pain. Participants (mean age=58 years) with KOA pain (n=146, 65% female) completed demographic, self-reported and experimental pain assessments including temporal summation and conditioned pain modulation along with a 3T high-resolution, T1-weighted anatomical scan at 2 study sites in the US. FreeSurfer software (v.7.1.0, http://surfer.nmr.mgh.harvard.edu ) was used to examine sex differences in gray matter volume and cortical thickness as well as associations with experimental variables. Maps were set at a vertex-wise threshold of P 0.05). The results suggest that brain morphological differences between females and men with KOA pain are associated with distinct pain modulatory measures in men, but not in women. Future studies are needed to characterize potential neurobiological mechanisms underlying endogenous pain modulatory capacity across the sexes to further understand the individualized pain experience. R01AG059809, R01AG067757.

A psychophysical study comparing massage to conditioned pain modulation: A single blind randomized controlled trial in healthy participants

IntroductionPain-inducing massage results in greater pain inhibition than pain free massage, suggesting a mechanism dependent on conditioned pain modulation (CPM). The purpose of this study was to test the hypothesis that pain inducing massage produces similar magnitude of reduction in pain sensitivity as a cold pressor task and that baseline conditioned pain modulation efficiency predicts pain inducing massage related hypoalgesia. MethodsSixty healthy participants were randomly assigned to receive either pain inducing massage to the neck, cold pressor task to the hand, or pain free massage to the neck. Participants also underwent pre and immediate post-intervention quantitative sensory testing. A repeated measures ANCOVA determined between group differences in pain sensitivity changes. ResultsPain inducing massage used as a conditioning stimulus resulted in comparable experimental pain sensitivity changes as a cold pressor task (p > 0.05). Pain intensity during the intervention demonstrated a weak correlation (r = 0.20, p = 0.12) with changes in pain sensitivity at a remote site. Individuals with an efficient CPM at baseline who received the pain inducing massage displayed greater increases in pressure pain threshold compared to individuals with a less efficient CPM indicating the potential benefit of treatment stratification by mechanism. ConclusionAlthough pain inducing massage resulted in less self-reported pain than a cold pressor task, both resulted in similar magnitude of the CPM response, suggesting shared underlying mechanisms. Understanding mechanisms of interventions can move us closer to mechanistic based treatments for pain which is consistent with a personalized medicine approach to care.

Differences in Psychosocial Factors and Experimental Pain Sensitivity Between Hispanics and Non-Hispanic Whites from the U.S.-Mexico Border.

Research suggests that ethnicity is a predictor of pain-related outcomes; however, studies comparing the differences in experimental pain sensitivity between Hispanics and non-Hispanic Whites (NHW) are scarce. This study investigated these differences between Hispanics and NHW from the U.S.- Mexico border. Fifty-eight healthy participants completed the survey packet, which included a demographic and a psychosocial factors questionnaire. Participants underwent quantitative sensory testing, which included heat pain threshold, heat pain tolerance, Suprathreshold Heat Pain Response (SHPR), and Conditioned Pain Modulation (CPM). SHPR was induced by repeated thermal stimuli in both thenar eminences. CPM was assessed using SHPR as the experimental stimulus and cold pressor task as the conditioning stimulus. Analyses showed significant differences in experimental pain measures believed to be representative of facilitatory pain processing including SHPR and heat pain threshold, where Hispanics reported significantly higher pain ratings than NHW. Hispanics also reported higher levels of ethnic identity and acculturation. However, these factors were not significantly associated with experimental pain sensitivity. The experimental pain sensitivity and psychosocial factors included in this study differed by ethnic group, where Hispanics reported significantly higher pain ratings, when compared with NHW. However, ethnic identity and acculturation were not associated with these pain-related outcomes. Overall, enhanced understanding by clinicians of pain sensitivity and disparities in the pain experience between ethnic groups allows for increased cultural sensitivity and can be used to optimize pain treatment on an individual-by-individual basis.

Changes in pain sensitivity and spinal stiffness in relation to responder status following spinal manipulative therapy in chronic low Back pain: a secondary explorative analysis of a randomized trial

BackgroundIn a prior randomized trial, we demonstrated that participants receiving spinal manipulative therapy at a pain-sensitive segment instead of a stiff segment experienced increased mechanical pressure pain thresholds. We hypothesized that the targeted segment mediated this increase through a segment-dependent neurophysiological reflective pathway. Presently, it is not known if this decrease in pain sensitivity is associated with clinical improvement. Therefore, we performed an explorative analysis to examine if changes in experimental pain sensitivity (mechanical and thermal) and lumbar stiffness were further dependent on clinical improvement in disability and patient-reported low back pain.MethodsThis study is a secondary explorative analysis of data from the randomized trial that compared 132 participants with chronic low back pain who received lumbar spinal manipulative therapy applied at either i) the stiffest segment or ii) the segment having the lowest pain threshold (i.e., the most pain-sensitive segment). We collected data at baseline, after the fourth session of spinal manipulation, and at 14-days follow-up. Participants were dichotomized into responders/non-responders using different clinical variables (disability and patient-reported low back pain) with varying threshold values (0, 30, and 50% improvement). Mixed models were used to assess changes in experimental outcomes (stiffness and pain sensitivity). The fixed interaction terms were time, segment allocation, and responder status.ResultsWe observed a significant increase in mechanical pressure pain thresholds for the group, which received spinal manipulative therapy at the most pain-sensitive segment independent of whether they improved clinically or not. Those who received spinal manipulation at the stiffest segment also demonstrated increased mechanical pain sensitivity, but only in the subgroup with clinical improvement. We did not observe any changes in lumbar stiffness.ConclusionOur results suggest the existence of two different mechanistic pathways associated with the spinal manipulation target. i) A decrease of mechanical pain sensitivity independent of clinical outcome (neurophysiological) and ii) a decrease as a reflection of the clinical outcome. Together, these observations may provide a novel framework that improves our understanding of why some respond to spinal manipulative therapy while others do not.Trial registrationClinicalTrials.gov identifier: NCT04086667 registered retrospectively September 11th 2019.

Effects of Mindfulness-Based Stress Reduction on Experimental Pain Sensitivity and Cortisol Responses in Women With Early Life Abuse: A Randomized Controlled Trial.

Early life abuse (ELAb) initiates pathophysiological cascades resulting in long-term maladaptive stress responsivity, hyperalgesia, and an increased risk of psychopathology. Mindfulness-based stress reduction (MBSR) is effective in modifying psychological and somatic symptoms; thus, we predicted that MBSR would be particularly efficacious for women with ELAb. Medically healthy women (mean age = 31 years) with or without a history of early (≤13 years) physical or sexual abuse provided self-report measures and were tested in the laboratory before and after randomization to standard MBSR (n = 52) or social support (SSG) (n = 60) for 8 weeks. The laboratory procedure involved pain testing using the cold pressor and temporal summation of heat pain (indexing central sensitization) procedures, and exposure to the Trier Social Stress Test. Plasma cortisol in response to the experimental protocol was assessed as area under the curve (AUC). The interventions differentially impacted pain sensitivity and cortisol AUC for women with ELAb, as MBSR increased the temporal summation of heat pain intensity ratings (p = .024) and reduced cortisol AUC (p = .004). For women without ELAb, MBSR decreased cold pressor tolerance (p = .045) and decreased the temporal summation of heat pain intensity ratings relative to SSG (p = .024). Both MBSR and SSG improved depression symptoms and emotion regulation abilities (p values < .001); however, MBSR was associated with greater benefits in describing emotions (p = .008) and impulse control (p = .017) for women with ELAb. Women with ELAb benefited from MBSR-specific improvements in central sensitization, mindfulness skills, and emotion regulation abilities. This is the first study to examine the efficacy of MBSR in modifying affective and somatic symptoms based on ELAb status and provides evidence for considering ELAb in tailoring treatment approaches.Trial Registration: ClinicalTrials.gov Identifier: NCT01995916; https://clinicaltrials.gov/ct2/show/NCT01995916.

Comparative Assessment of Nociceptive Mechanisms in Endometriosis Vs. Primary Dysmenorrhea

Study Objective Endometriosis-associated pelvic pain patients frequently experience both cyclical menstrual pain and chronic pelvic pain, suggesting dysregulated central sensory processes. The amount that chronic pain experience affects experimental pain sensitivity in comparison to cyclical menstrual pain exposure, is unknown. Design Subanalysis of a broader, ongoing longitudinal study of concomitant menstrual pain and bladder pain in both chronic and cyclical pain cohorts of women. We characterized body, and vaginal mechanical sensitivity (pressure algometry) as well as visceral hypersensitivity (noninvasive cystometry) during the luteal phase. Participants completed Patient Reported Outcomes Measurement System (PROMIS) anxiety, depression, fatigue and sleep measures as possible QST covariates. Contrasts were done with Wilcoxon rank-sum tests. Setting Patients enrolled from 8/2014 to 12/2018 at Evanston Hospital. Patients or Participants Women with dysmenorrhea (DYS, n=153), healthy controls (n=40), and surgically confirmed endometriosis (n=20). Interventions N/A Measurements and Main Results DYS and endometriosis participants had more vaginal mechanical pain sensitivity than controls (median pressure pain threshold 7.3 N/cm2 [interquartile range {IQR} 4.2, 11.0], 5.3[IQR 3.3, 8.9] vs. 10.6[IQR 7.3, 14.6], p 0.05). Conclusion Endometriosis’ distinct nociceptive profile compared with pure dysmenorrhea suggests chronic pain experience has only a modest additional impact on mechanical hypersensitivity, with far greater impact on visceral (bladder) hypersensitivity.

The effect of music on pain sensitivity in healthy adults

ABSTRACT Background Previous work suggests mediating effects of music on acute pain processing. This quasi-experimental pilot study examined the effects of music on experimental pain sensitivity. Methods Healthy adults (N = 40) completed quantitative sensory tests during three music conditions (silence, listening, and singing). Repeated Measures ANOVA , Friedman’s Test, and post hoc comparisons determined differences in pain intensity and time to cold pain threshold and tolerance between conditions.. Pearson partial correlations evaluated the association of musical factorswith pain sensitivity. Results Participants demonstrated longer time intervals until perceiving pain and tolerated pain for longer durations when singing compared to listening. Greater self-reported singing proficiency was associated with higher tolerance. Several musical factors were significantly correlated with time from pain threshold to reaching tolerance. Conclusion Singing during an acute painful stimulus may increase tolerance. Various musical characteristics impact volunteers’ central pain responses and singing may be an important adjunct pain management strategy.

Changes in Experimental Pain Sensitivity from Using Home-Based Remotely Supervised Transcranial Direct Current Stimulation in Older Adults with Knee Osteoarthritis.

The present study examined the effects of home-based remotely supervised transcranial direct current stimulation on quantitative sensory testing measurements in older adults with knee osteoarthritis. Participants were hypothesized to experience improved pain measurements over time. Open-label, single-arm trial. Southeast Texas between March and November 2018 at a nursing school and participant homes. Older adults (aged 50-85 years) with self-reported unilateral or bilateral knee osteoarthritis pain who met eligibility criteria set by the American College of Rheumatology. The intervention was applied with a constant current intensity for 20 minutes every weekday for two weeks (10 total sessions). Quantitative measures of pain were collected three times over 10 days (days 1, 5, and 10) and included heat threshold and tolerance, pressure pain threshold, punctate mechanical pain, pain, and conditioned pain modulation. Analyses used nonparametric tests to evaluate differences between day 1 and day 10. Generalized linear mixed models were then used to evaluate change across all three time points for each measure. Bayesian inference was used to provide the posterior probability of longitudinal effects. Nonparametric tests found improvements in seven measures, and longitudinal models supported improvements in 10 measures, with some nonlinear effects. The home-based, remotely supervised intervention improved quantitative measurements of pain in older adults with knee osteoarthritis. This study contributes to the growing body of literature supporting home-based noninvasive stimulation interventions.

The Effects of Posttraumatic Stress and Trauma-Focused Disclosure on Experimental Pain Sensitivity Among Trauma-Exposed Women.

Previous studies evaluating the impact of trauma history and posttraumatic stress disorder (PTSD) on pain sensitivity have yielded inconsistent findings. The presence of trauma-related negative affective states may account for these discrepancies. The current study aimed to evaluate the effect of PTSD and trauma-related negative affect on sensory, affective, physiological, and neuroendocrine responses to an experimental pain task. Trauma-exposed adult women (N = 87) with or without probable PTSD underwent an emotional disclosure paradigm during which they wrote about a traumatic event or a neutral topic. Participants then completed a pain induction procedure. Sensory and affective reports of pain, as well as physiological and neuroendocrine reactivity, were assessed. Compared to women without PTSD, those with PTSD demonstrated decreased sensory pain responses, ηp ² = .11, including increased time to pain detection (i.e., threshold) and ability to withstand the pain stimuli (i.e., tolerance) after accounting for relevant covariates. Women with PTSD also demonstrated increased cortisol reactivity following the pain stimulus, ηp ² = .06. The main and interactive effects of PTSD group and writing condition did not significantly predict alterations in affective reports of pain or heart rate reactivity. The results suggest that PTSD symptoms may contribute to alterations in pain sensitivity in trauma-exposed women, but this association is complex and requires further exploration.

Understanding the relationship between features associated with pain-related disability in people with painful temporomandibular disorder: an exploratory structural equation modeling approach.

Pain-related disability is a multifaceted construct that refers to the impact of pain on an individual's capacity to fulfill their self-defined and social roles. This research examined the relationship between clinical, psychological, and pain sensitivity factors and pain-related disability among adults with chronic temporomandibular disorder (TMD). We analyzed data from a cross-sectional community-based sample of 1088 men and women with chronic TMD. We first constructed and tested a measure of pain-related disability (ie, pain impact), including a variable assessing presenteeism, created measurement models of jaw limitation, psychological unease (negative affect, somatic symptoms, and catastrophizing), and experimental pain sensitivity (eg, pressure pain threshold, thermal tolerance, and mechanical pressure pain threshold). Subsequently, latent variables were combined in a structural equation model. Participants (n = 1088) were 18 to 44 years old (mean 29.2, SD ± 7.8) whose chronic TMD had persisted, on average, for 6.9 years (SD ± 6.4). A model of pain-related disability, jaw limitation, and psychological unease was created and refined with exploratory model revisions to account for correlation among variables. Estimation of the final model indicated excellent fit with the data (root-mean-square error of approximation = 0.048, root-mean-square error of approximation 90% confidence interval [CI] 0.043-0.053, comparative fit index = 0.956, standardized root-mean-square residual = 0.040). Jaw functional limitation and psychological unease was strongly related to pain-related disability. Experimental pain sensitivity was removed from our model because of weak direct effect and the burden of performing experimental pain sensitivity testing in a clinical setting. The final model explained 78% of the variance in pain-related disability.

Increased Experimental Pain Sensitivity in Chronic Pain Patients Who Developed Opioid Use Disorder.

Although the great majority of individuals who take opioids for chronic pain use them appropriately and to good effect, a certain minority will develop the problematic outcome of opioid use disorder (OUD). Characteristics associated with the development of OUD in individuals with chronic pain have been described; however, relatively unexplored is how sensitivity to pain is associated with OUD outcomes. We examined for differences in response to static and dynamic experimental pain stimuli between individuals with chronic nonmalignant pain who developed OUD after starting opioid therapy (n=20) and those on opioid therapy who did not (n=20). During a single experimental session, participants underwent cold pressor and quantitative sensory testing pain assays, and objective and subjective responses were compared between groups; the role of pain catastrophizing in mediating pain responses was examined. Results suggested that both groups of opioid-dependent patients were similarly hyperalgesic to the cold pressor pain stimulus, with nonparametric testing revealing worsened central pain sensitization (temporal summation) in those who developed OUD. Significant group differences were evident on subjective ratings of experimental pain, such that those who developed OUD rated the pain as more severe than those who did not. Pain catastrophizing was unrelated to pain responses. Despite the small sample size and cross-sectional design, these findings suggest that experimental pain testing may be a novel technique in identifying patients with chronic pain likely to develop OUD, in that they are likely to evidence exacerbated temporal summation and to rate the associated pain as more severe.

No Evidence of Altered Reactivity to Experimentally Induced Pain Among Regular Cannabis Users.

Recent years have seen an increase in the adoption of cannabinoid medicines, which have demonstrated effectiveness for the treatment of chronic pain. However, the extent to which frequent cannabis use (CU) influences sensitivity to acute pain has not been systematically examined. Such a determination is clinically relevant in light of hypersensitivity to pain associated with prolonged use of other analgesics such as opioids, and reports of increased pain sensitivity to experimentally induced pain during acute cannabis intoxication. This study explored differences in measures of pain intensity and tolerance. The authors hypothesized that individuals who report frequent CU would demonstrate greater experimental pain sensitivity. Frequent cannabis users (≥3× per week; n=40) and nonusers (n=40) were compared on pain sensitivity, pain tolerance, and pain intensity in response to a cold-pressor task. Group differences were examined. Frequent CU was not associated with hyperalgesia as cannabis users and nonusers did not exhibit differences on measures of pain tolerance (t (78)=-0.05; P=0.96), sensitivity (t (78)=-0.83; P=0.41), or intensity (t (78)=0.36; P=0.72). Frequent cannabis users did not demonstrate hyperalgesia. This finding should help to inform evaluations of the relative harms and benefits of cannabis analgesic therapies.

Feasibility and efficacy of remotely supervised cranial electrical stimulation for pain in older adults with knee osteoarthritis: A randomized controlled pilot study

Cranial electrical stimulation (CES) is a noninvasive brain stimulation technique that has been shown to improve pain. However, few studies have investigated the potential benefits associated with remotely supervised CES in older adults with knee osteoarthritis (OA). The aim of this study was to examine the feasibility and preliminary efficacy of remotely supervised CES via secure videoconferencing software on clinical pain severity, experimental pain sensitivity, and pain-related cortical response in older adults with knee OA. Thirty participants with symptomatic knee OA pain were randomly assigned to receive 10 daily sessions (60 min each) of remotely supervised CES (n = 15) or sham CES (n = 15) over two weeks. We measured clinical pain severity via a Numeric Rating Scale, experimental pain sensitivity (e.g., heat pain sensitivity, pressure pain sensitivity, and conditioned pain modulation) using quantitative sensory testing, and pain-related cortical response via functional near-infrared spectroscopy imaging. We also measured participant satisfaction with treatment using the Client Satisfaction Questionnaire. Active CES significantly reduced scores on the Numeric Rating Scale and increased heat pain threshold, pressure pain thresholds, and conditioned pain modulation. We also found significant changes in pain-related cortical hemodynamic activity after CES. Participants tolerated CES well without serious adverse effects and were satisfied with the treatment. Our findings demonstrate promising clinical efficacy of remotely supervised CES for older adults with knee OA.

Pain Sensitivity Modifies Risk of Injury-Related Temporomandibular Disorder

This study evaluates contributions of jaw injury and experimental pain sensitivity to risk of developing painful temporomandibular disorder (TMD). Data were from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) nested case-control study of incident painful TMD. Injury and subsequent onset of painful TMD were monitored prospectively for ≤5 y in a community-based sample of 409 US adults who did not have TMD when enrolled. At baseline, thermal-pressure and pinprick pain sensitivity, as potential effect modifiers, were measured using quantitative sensory testing. During follow-up, jaw injury from any of 9 types of potentially traumatic events was determined using quarterly (3-monthly) health update questionnaires. Study examiners classified incident painful TMD, yielding 233 incident cases and 176 matched controls. Logistic regression models, estimated incidence odds ratios (IORs), and 95% confidence limits (CLs) were used for the association between injury and subsequent onset of painful TMD. During follow-up, 38.2% of incident cases and 13.1% of controls reported 1 or more injuries that were 4 times as likely to be intrinsic (i.e., sustained mouth opening or yawning) as extrinsic (e.g., dental visits, whiplash). Injuries due to extrinsic events (IOR = 7.6; 95% CL, 1.6–36.2), sustained opening (IOR = 5.4; 95% CL, 2.4–12.2), and yawning (IOR = 3.4; 95% CL, 1.6–7.3) were associated with increased TMD incidence. Both a single injury (IOR = 6.0; 95% CL, 2.9–12.4) and multiple injuries (IOR = 9.4; 95% CL, 3.4,25.6) predicted greater incidence of painful TMD than events perceived as noninjurious (IOR = 1.9; 95% CL, 1.1–3.4). Injury-associated risk of painful TMD was elevated in people with high sensitivity to heat pain (IOR = 7.4; 95% CL, 3.1–18.0) compared to people with low sensitivity to heat pain (IOR = 3.9; 95% CL, 1.7–8.4). Jaw injury was strongly associated with elevated painful TMD risk, and the risk was amplified in subjects who had enhanced sensitivity to heat pain at enrollment. Commonly occurring but seemingly innocuous events, such as yawning injury, should not be overlooked when judging prognostic importance of jaw injury.

Experimental Pain Sensitivity in Subjects with Temporomandibular Disorders and Multiple Other Chronic Pain Conditions: The OPPERA Prospective Cohort Study.

To investigate associations between experimental pain sensitivity and five chronic pain conditions among 655 participants in the OPPERA study. Quantitative sensory tests were used to measure sensitivity to three modalities of nociception: blunt pressure pain, mechanical pinprick pain, and thermal heat pain. Participants were also classified according to the presence or absence of five chronic pain conditions: temporomandibular disorders, headache, low back pain, irritable bowel syndrome, and fibromyalgia. Univariate analyses found each modality to be significantly associated with at least one pain condition, most consistently for pressure pain sensitivity (8 of 15 instances) and least consistently for heat pain sensitivity (5 of 35 instances). Yet, multivariable analyses that evaluated the independent contributions of all five pain conditions found few significant associations (12 of 75 instances). Instead, pain sensitivity consistently varied according to the total number of pain conditions a person experienced, implying that the combination of pain conditions influences each nociceptive modality. When evaluating nociceptive sensitivity in a chronic pain patient, comorbid pain conditions should be considered, as the more salient feature underlying sensitivity is likely the number rather than the type(s) of pain conditions.

COMT gene variants and β-endorphin levels contribute to ethnic differences in experimental pain sensitivity.

This cross-sectional study investigated whether the catechol-O-methyltransferase (COMT) gene acts as a significant regulator of pain signaling pathways, regulates β-endorphin, and contributes to ethnic differences in pain sensitivity. One-hundred-sixty healthy subjects were enrolled in this study, with Han and Uyghur groups each consisting of 80 participants. Subjects went through six pain threshold experiments. From venous blood, COMT polymorphisms were genotyped, and serum β-endorphin levels were measured. Bivariate correlation analysis and multiple linear regression were used to identify the relationships among genotypes or β-endorphin levels and different types of pain thresholds. Han and Uyghur ethnic differences were determined in terms of acute-pressure pain-perception thresholds, blunt-pressure pain-perception thresholds, blunt-pressure pain-tolerance thresholds, electric pain-tolerance thresholds, β-endorphin levels, and distributions of rs4680 and rs4633 COMT polymorphisms. β-endorphin levels did not correlate with COMT rs4680 or rs4633 genotypes in both Han and Uyghur. Statistical predictors for a lower pain-threshold performance included being young, Uyghur, female, and having a low body mass index, low β-endorphin level, and the rs4680 GA or GG allele. There is the significant difference in pain sensitivity between healthy Han and Uyghur. COMT gene variants and β-endorphin levels contribute to ethnic differences in pain sensitivity.