Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delta-9-tetrahydrocannabinol (dronabinol), as well as their effects on physical and cognitive functioning, and human abuse potential (HAP) outcomes among individuals with knee osteoarthritis (KOA). This was a within-subject, double-blind, randomized, placebo-controlled study. Participants (N = 37; 65% women; mean age = 62) diagnosed with knee osteoarthritis of ≥3/10 average pain intensity were included. Participants received (1) placebo-placebo, (2) hydromorphone (4 mg)-placebo; (3) dronabinol (10 mg)-placebo, and (4) hydromorphone (4 mg)-dronabinol (10 mg). Clinical and experimentally-induced pain, physical and cognitive function, subjective drug effects, HAP, adverse events, and pharmacokinetics were evaluated. No significant analgesic effects were observed for clinical pain severity or physical functioning across all drug conditions. Little enhancement of hydromorphone analgesia by dronabinol was observed on evoked pain indices. While subjective drug effects and some HAP ratings were increased in the combined drug condition, these were not significantly increased over the dronabinol alone condition. No serious adverse events were reported; hydromorphone produced more mild adverse events than placebo, but hydromorphone + dronabinol produced more moderate adverse events than both placebo and hydromorphone alone. Only hydromorphone impaired cognitive performance. Consistent with laboratory studies on healthy adults, the present study shows minimal benefit of combining dronabinol (10 mg) and hydromorphone (4 mg) for analgesia and improving physical functioning in adults with KOA.

A Preliminary Examination of the Effects and Mechanisms of Cognitive Behavioral Therapy for Insomnia on Systemic Inflammation Among Patients with Knee Osteoarthritis.

BACKGROUND: Systemic inflammation, particularly the elevation of interleukin-6 (IL-6), plays an important role in the maintenance and progression of knee osteoarthritis. Insomnia, being highly prevalent in knee osteoarthritis, is understood to be a risk factor for systemic inflammation. The present study examined if cognitive behavioral therapy for insomnia (CBT-I) would reduce circulating IL-6 levels to a larger extent than the active control condition via greater improvement in sleep maintenance disturbance at mid-treatment, among individuals with knee osteoarthritis and insomnia disorder. METHODS: This is an ancillary study (N = 64) from a larger double-blind, randomized, active controlled clinical trial. Serum IL-6 was measured at baseline, post-treatment, and 3- and 6-month follow-ups. Sleep was measured by daily sleep diaries. RESULTS: Overall, there was no significant IL-6 trajectory differences between CBT-I and the active control (p = .64). Compared to the active control, CBT-I demonstrated greater improvement in sleep maintenance disturbance at mid-treatment (p = .01), which, in turn, was significantly associated with lower levels of IL-6 at 3-month follow-up (p < .05). Sleep maintenance disturbance at mid-treatment did not significantly predict changes in IL-6 levels at post-treatment (p = .43) and 6-month follow-up (p = .90). CONCLUSIONS: Our study demonstrates that CBT-I can be efficacious in improving sleep maintenance disturbance among individuals with knee osteoarthritis and insomnia disorder. However, no convincing evidence was found that CBT-I can substantially reduce IL-6 levels via improvement in sleep. CBT-I alone may not be effective in reducing systematic inflammation in this clinical population. TRIAL REGISTRATION: NCT00592449.

The use of telemedicine for perioperative pain management during the COVID-19 pandemic.

INTRODUCTION: Using a human factors engineering approach, the Johns Hopkins Personalized Pain Program adopted telemedicine for perioperative pain management in response to the COVID-19 pandemic. This study examines the impact of telemedicine adoption on the quality and outcomes of perioperative pain management. METHODS: A mixed-methods study with a convergent parallel design was conducted. From June 2017 to December 2021, 902 patients participated in the Personalized Pain Program. Quantitative data on daily opioid consumption, pain severity and interference, physical and mental health status, and patient satisfaction and engagement were continuously collected with all patients using chart review and patient surveys. Beginning 23 March 2020, the Personalized Pain Program transitioned to telemedicine. A pre-post quasi-experimental design was used to examine the impact of telemedicine. In addition, qualitative interviews were conducted with 3 clinicians and 17 patients to explore their experience with telemedicine visits. RESULTS: The monthly number of new patients seen in the Personalized Pain Program did not significantly change before and after telemedicine adoption. Compared to patients having in-person visits before the pandemic, patients having telemedicine visits during the pandemic achieved comparable improvements in daily opioid consumption, pain severity and interference, and physical health status. While telemedicine helped overcome many challenges faced by the patients, the limitations of telemedicine were also discussed. CONCLUSION: The COVID-19 pandemic stimulated the use of telemedicine. To facilitate telemedicine adoption beyond the pandemic, future research is needed to examine best practices for telemedicine adoption and provide additional evidence on the effectiveness of telemedicine.

A multidisciplinary transitional pain service to improve pain outcomes following trauma surgery: a preliminary report.

OBJECTIVES: Trauma (i.e., musculoskeletal injury from a blunt or penetrating force) can change the trajectory of a person's life. Patients often experience chronic pain, reduced quality of life, long-term opioid therapy, and psychiatric comorbidities after trauma surgery. This case report presents clinical outcomes of four patients who received postsurgical pain care in a transitional pain service (TPS) that provides long-term coordinated multimodal pain care, opioid tapering plans, and psychiatric care. METHODS: The Personalized Pain Program (PPP) measures prescription opioid use and patient-reported outcomes: pain severity and pain interference (Brief Pain Inventory), pain catastrophizing (Pain Catastrophizing Scale), insomnia severity (Insomnia Severity Index), physical and mental health functioning (SF-12 pre-COVID-19; SF-36 during COVID-19 pandemic) at initial and subsequent clinic visits. RESULTS: All four patients reduced their postsurgical opioid use with concurrent reductions in pain and improved functioning while receiving postoperative care in the PPP (average length of treatment: 2.8 years). Psychiatric co-treatment addressed the onset or exacerbation of mental health comorbidities following trauma. CONCLUSIONS: Long-term multidisciplinary pain care may improve post-trauma recovery and reduce risks of long-term opioid therapy and disability. Prospective studies are needed to evaluate the effectiveness of TPSs for patients undergoing trauma surgery.

Patient Experiences and Clinical Outcomes in a Multidisciplinary Perioperative Transitional Pain Service.

Siloed pain management across the perioperative period increases the risk of chronic opioid use and impedes postoperative recovery. Transitional perioperative pain services (TPSs) are innovative care models that coordinate multidisciplinary perioperative pain management to mitigate risks of chronic postoperative pain and opioid use. The objective of this study was to examine patients' experiences with and quality of recovery after participation in a TPS. Qualitative interviews were conducted with 26 patients from The Johns Hopkins Personalized Pain Program (PPP) an average of 33 months after their first PPP visit. A qualitative content analysis of the interview data showed that participants (1) valued pain expectation setting, individualized care, a trusting patient-physician relationship, and shared decision-making; (2) perceived psychiatric treatment of co-occurring depression, anxiety, and maladaptive behaviors as critical to recovery; and (3) successfully sustained opioid tapers and experienced improved functioning after PPP discharge. Areas for improved patient-centered care included increased patient education, specifically about the program, continuity of care with pain specialists while tapering opioids, and addressing the health determinants that impede access to pain care. The positive patient experiences and sustained clinical benefits for high-risk complex surgical patient support further efforts to implement and adapt similar models of perioperative pain care.

A comparison of cognitive behavioral therapy for insomnia to standard of care in an outpatient substance use disorder clinic embedded within a therapeutic community: a RE-AIM framework evaluation.

BACKGROUND: Rates of substance use disorders (SUDs) continue to rise in the USA with parallel rises in admissions to outpatient SUD treatment programs. Insomnia symptoms reduce treatment adherence, trigger relapse, and generally undermine SUD recovery efforts. Cognitive-behavioral therapy for insomnia (CBT-I) is the first-line treatment recommended for chronic insomnia. No study has examined the effectiveness of CBT-I for individuals who recently entered an outpatient SUD treatment program embedded within a therapeutic community (i.e., long-term drug-free residential setting). METHODS: A randomized controlled trial conducted at a SUD program embedded in a therapeutic community aimed to compare group-based CBT-I (gCBT-I) (N = 10) with the standard of care (SOC) (N = 11) among individuals who have SUDs and comorbid insomnia. We present a RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework evaluation to provide empirical data on gCBT-I feasibility and facilitators and barriers of conducting an insomnia-focused clinical effectiveness study within a therapeutic community. RESULTS: Participants in both study arms reported moderately severe insomnia symptoms at admission and reductions in insomnia symptoms over time. Among participants who completed the Insomnia Severity Index (ISI) beyond admission, ISI decreased to ≤ 8 (the clinical cutoff for mild insomnia) in 80% of individuals in the gCBT-I group compared with 25% of individuals in the SOC group. A RE-AIM framework evaluation showed initial success with Reach and Adoption while Implementation, and Maintenance were limited. Effectiveness was inconclusive because of challenges with recruitment, intervention integrity, and missing data that precluded meeting the planned recruitment and study aims and led to study termination. Coordination and communication with staff and leadership facilitated gCBT-I implementation, yet well-known CBT-I barriers including time- and resource-intensive sleep medicine training for interventionalists and maintenance of treatment integrity during an 8-week intervention limited gCBT-I sustainability. CONCLUSIONS: This analysis supports the feasibility of conducting behavioral sleep medicine research in outpatient SUD treatment programs embedded within therapeutic communities. Implementation of an insomnia-focused intervention was widely accepted by patients and providers and has potential to address insomnia symptoms in early SUD recovery. Addressing patient- and organizational-level implementation barriers may enhance the sustainability and scalability of sleep interventions and provide new hope to effectively treat insomnia among people living with SUDs. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03208855. Registered July 6, 2017https://clinicaltrials.gov/ct2/show/NCT03208855?term=NCT03208855&draw=2&rank=1.

Patient engagement and prescription opioid use in perioperative pain management.

OBJECTIVE: To examine (1) patient perceptions regarding their engagement and the engagement of their families in perioperative pain management, (2) demographic and clinical characteristics associated with perceived patient and family engagement, and (3) the association between perceived patient and family engagement and patient outcomes. DESIGN: A prospective, observational study. SETTING: The Personalized Pain Program (PPP) at the Johns Hopkins Hospital in Baltimore, Maryland. PARTICIPANTS: Patients having more than one visit to the PPP. INTERVENTIONS: n/a. MAIN OUTCOME MEASURES: Since the inception of the PPP, patients were surveyed prior to each clinic visit to assess their pain severity and interference using the Brief Pain Inventory. Starting August 22, 2018, two additional questions were added to the survey to assess patient perceptions of their engagement and the engagement of their families in perioperative pain management. In addition, electronic medical records were reviewed to collect data on daily opioid consumption during the first and last PPP visits presurgery and post-surgery. RESULTS: The final analysis included 511 survey responses from 155 patients. Perceived engagement of the patient in perioperative pain management improved over time (p < .001) and was significantly associated with reduction in prescription opioid consumption after surgery (coef = 12.7, SE = 5.8, p = .031). CONCLUSIONS: Surgical patients and their family members should be actively engaged in perioperative pain management to improve prescription opioid use and the quality and safety of perioperative care.

Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model.

This Phase II study evaluated analgesia, abuse liability, and cognitive performance of hydromorphone and oral delta-9-tetrahydrocannabinol (THC; dronabinol) using a within-subject, double-blind, randomized, placebo-controlled, human laboratory trial. Healthy adults (N = 29) with no history of drug use disorder received combinations of placebo, hydromorphone (4 mg; oral), and dronabinol (2.5 mg, 5.0 mg, 10 mg; oral). Primary outcomes were quantitative sensory testing (QST) measures of acute (thermal, pressure pain; thermal, punctate probe temporal summation; cold pressor; conditioned pain modulation) and chronic pain (capsaicin 10% topical cream with thermal rekindling), measures of drug abuse liability, cognitive functioning, and adverse events. Subgroup analyses were conducted within opioid-responders (endorsed >20 on a Drug Effect visual analog scale during the hydromorphone-only condition) and nonresponders. A consistent dose-effect relationship of dronabinol on hydromorphone across all measures was not observed. Analgesia only improved in the hydromorphone + dronabinol 2.5 mg condition. Hydromorphone + dronabinol 2.5 mg showed the lowest and hydromorphone+dronabinol 5 mg showed the highest risk for abuse. Hydromorphone+dronabinol 10 mg produced a high rate of dysphoric effects, and hydromorphone+dronabinol 5 mg and hydromorphone + dronabinol 10 mg produced AEs. Subgroup analyses showed subjective effects and abuse risk was increased among opioid responders and largely absent among nonresponders. Overall, only hydromorphone+dronabinol 2.5 mg modestly enhanced hydromorphone-based analgesia and hydromorphone + dronabinol 5 mg and 10 mg increased risk for abuse and AEs. These data can help inform opioid-sparing efforts in clinical pain populations. Demonstration that potential opioid effects varied as a function of participant opioid sensitivity (e.g., responder status) is a novel finding that warrants additional research.

Temporal Association of Pain Catastrophizing and Pain Severity Across the Perioperative Period: A Cross-Lagged Panel Analysis After Total Knee Arthroplasty.

OBJECTIVE: Although numerous studies show that preoperative pain catastrophizing is a risk factor for pain after total knee arthroplasty (TKA), little is known about the temporal course of the association between perioperative pain catastrophizing and pain severity. The present study investigated temporal changes and their dynamic associations between pain catastrophizing and pain severity before and after TKA. DESIGN: A secondary data analysis of a larger observational parent study featuring prospective repeated measurement over 12 months. SETTING: Dual-site academic hospital. SUBJECTS: A total of 245 individuals who underwent TKA. METHODS: Participants completed pain catastrophizing and pain severity questionnaires at baseline, 6 weeks, and 3, 6, and 12 months after TKA. Cross-lagged panel analysis was conducted with structural equation modeling including age, sex, race, baseline anxiety, and depressive symptoms as covariates. RESULTS: Reduction in pain catastrophizing from baseline to 6 weeks after TKA was associated with lower pain severity at 3 months after TKA (standardized ß = 0.14; SE = 0.07, P = 0.046), while reduction in pain severity at 6 weeks after TKA was not associated with pain catastrophizing at 3 months after TKA (P = 0.905). In the chronic postsurgical period (>3 months), pain catastrophizing at 6 months after TKA predicted pain severity at 12 months after TKA (ß = 0.23, P = 0.009) with controlling for auto-correlation and covariates, but not vice versa. CONCLUSIONS: We provide evidence that changes in pain catastrophizing from baseline to 6 weeks after TKA are associated with subsequent pain severity. Future studies are warranted to determine whether targeting pain catastrophizing during the perioperative period may improve clinical outcomes for individuals undergoing TKA.

Addressing the Opioid Crisis One Surgical Patient at a Time: Outcomes of a Novel Perioperative Pain Program.

Opioid prescriptions in the surgical setting have been implicated as contributors to the opioid epidemic. The authors hypothesized that a multidisciplinary approach to perioperative pain management for patients on chronic opioid therapy could decrease postoperative opioid requirements while reducing postoperative pain scores and improving functional outcomes. Therefore, a Perioperative Pain Program (PPP) for chronic opioid users was implemented. This study presents outcomes from the first 9 months of the PPP. Sixty-one patients met the inclusion criteria. Opioid consumption in morphine milligram equivalent (MME) was calculated and physical and health status of patients was assessed with the Brief Pain Inventory, Short-Form McGill Pain Questionnaire, and Short Form-12. Preliminary results showed significant reduction in MME, improved pain scores, and improved function for surgical patients on chronic opioids. PPP effectively reduced opioid usage without negatively influencing patient-reported outcomes, such as physical pain score assessment and health-related quality of life.

Ethnic disparities in pain processing among healthy adults: µ-opioid receptor binding potential as a putative mechanism.

Although ethnic differences in pain perception are well documented, the underlying mechanism for these outcomes has not been established. µ-opioid receptor (MOR) function might contribute to this disparity, given that MORs play a key role in pain sensitivity and modulation. However, no study has characterized ethnic differences in MOR physiology. This study sought to address this knowledge gap by examining differences in µ-selective agonist binding potential (BPND; [C]-Carfentanil) between 27 non-Hispanic black (NHB) and 27 demographically similar, non-Hispanic white participants. Participants completed questionnaires and two 90-minute high-resolution research tomograph positron emission tomography (PET) imaging sessions. During PET imaging, a capsaicin or control cream was applied to individuals' arms, and pain ratings were collected. Bonferroni-corrected PET volumes of interest analyses revealed significantly greater [C]-Carfentanil BPND among NHB participants in bilateral ventral striatum ([left]: F1,52 = 16.38, P < 0.001; [right]: F1,52 = 21.76, P < 0.001), bilateral dorsolateral prefrontal cortex ([left] F1,52 = 17.3, P < 0.001; [right]: F1,52 = 14.17, P < 0.001), bilateral subgenual anterior cingulate cortex ([left]: F1,52 = 10.4, P = 0.002; [right]: F1,52 = 12.91, P = 0.001), and right insula (F1,52 = 11.0, P = 0.002). However, there were no significant main effects of condition or ethnicity × condition interaction effects across models, likely attributable to individual variability in the direction of change within groups. BPND values were significantly correlated with pain ratings collected during the capsaicin condition (r range = 0.34-0.46, P range = 0.01-0.001). Results suggest that NHB individuals might have generally greater unoccupied MOR density than non-Hispanic white peers. Findings have implications for physiological differences underlying ethnicity-related pain disparities. If replicated, these results further emphasize the need for tailored treatments in historically underserved populations.

A model for an institutional response to the opioid crisis.

The use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. Physicians, policymakers, and researchers are focused on finding ways to decrease opioid use and overdose. This crisis calls for a coordinated response that includes the entire healthcare sector. In this work, the authors lay out a blueprint for such a response at the level of the academic medical center. The proposed model is a comprehensive opioid overdose prevention, response, and education program to evaluate, monitor, and address prescription opioid-related adverse events and addiction among all patients within a healthcare system. The approach includes three inter-related elements: (1) creation of an organizational structure that is subdivided into subcommittees to facilitate cross-functional collaboration and implementation. These subcommittees will focus on Research and Design, Implementation, Advisory, and Compliance with the recommendation. (2) Development of an effective communication plan throughout the institution to enable the organization to function seamlessly and efficiently as a single unit, (3) development of a data tracking and reporting system that intended to have a 360° view of all aspects of opioid prescription and downstream patient outcomes. The most effective response system will require an organizational structure that facilitates the ad hoc constitution of cross-functional teams with members drawn from all levels of the organizational hierarchy (executive leadership to frontline staff). Such a structure provides the teams with immediate solutions as developed by the frontline staff and authority to remove institutional barriers that may delay or limit the successful implementation. The model described was developed in our institution by a cross-functional team that included members from the Johns Hopkins School of Medicine and Johns Hopkins University Carey Business School, Department of Operations Management. The multidisciplinary nature of collaboration allowed us to develop a model for an immediate institution-wide response to the opioid crisis, and one that other healthcare organizations could adopt with local modification as a template for execution. The model also meant to serve as a template for an institutional rapid-response that can be seamlessly implemented during any future drug-related crisis or epidemic.

Sex differences in measures of central sensitization and pain sensitivity to experimental sleep disruption: implications for sex differences in chronic pain.

Study Objectives: Females demonstrate heightened central sensitization (CS), a risk factor for chronic pain characterized by enhanced responsivity of central nervous system nociceptors to normal or subthreshold input. Sleep disruption increases pain sensitivity, but sex has rarely been evaluated as a moderator and few experiments have measured CS. We evaluated whether two nights of sleep disruption alter CS measures of secondary hyperalgesia and mechanical temporal summation in a sex-dependent manner. We also evaluated differences in measures of pain sensitivity. Methods: Seventy-nine healthy adults (female n = 46) participated in a randomized crossover experiment comparing two consecutive nights of eight pseudorandomly distributed forced awakenings (FA [-200 min sleep time]) against two nights of undisturbed sleep (US). We conducted sensory testing the mornings following Night 2; the heat-capsaicin pain model was used to induce secondary hyperalgesia. Results: FA reduced total sleep time (REM and NREM Stage 3) more profoundly in males. We observed divergent, sex-dependent effects of FA on secondary hyperalgesia and temporal summation. FA significantly increased secondary hyperalgesia in males and significantly increased temporal summation in females. Sex differences were not attributable to differential sleep loss in males. FA also significantly reduced heat-pain threshold and cold pressor pain tolerance, independently of sex. Conclusions: Sleep disruption enhances different pain facilitatory measures of CS in males and females suggesting that sleep disturbance may increase risk for chronic pain in males and females via distinct pathways. Findings have implications for understanding sex differences in chronic pain and investigating sleep in chronic pain prevention efforts.

An Innovative Perioperative Pain Program for Chronic Opioid Users: An Academic Medical Center's Response to the Opioid Crisis.

Increased utilization of prescription opioids for pain management has led to a nationwide public health crisis with alarming rates of addiction and opioid-related deaths. In the surgical setting, opioid prescriptions have been implicated as a contributing factor to the opioid epidemic. The authors developed an innovative model to address aspects of pain management and opioid utilization during preoperative evaluation, acute surgical hospitalization, and postoperative follow-up for chronic opioid users. This program involves multidisciplinary teams that include acute and chronic pain specialists, psychiatrists, integrative medicine specialists, and physical medicine and rehabilitation services. It also features a novel infrastructure for triage and pain management education and treatment. Individualized patient plans are devised that can include preoperative opioid weaning, regional anesthesia that minimizes opioid use, and multimodal techniques for surgical pain treatment. Multidisciplinary programs such as this have the potential to both improve perioperative pain control and prevent escalation of opioid use among chronic opioid users.

Comorbid chronic pain and opioid use disorder: literature review and potential treatment innovations.

Chronic pain (CP) and opioid use disorder (OUD) remain challenging complex public health concerns. This is an updated review on the relationship between CP and OUD and the use of stepped care models for assessment and management of this vulnerable population. A literature search was conducted from 2008 to the present in PubMed, Embase, and PsycInfo using the terms pain or chronic pain and opioid-related disorders, opiate, methadone, buprenorphine, naltrexone, opioid abuse, opioid misuse, opioid dependen*, heroin addict, heroin abuse, heroin misuse, heroin dependen*, or analgesic opioids, and stepped care, integrated services, multidisciplinary treatment, or reinforcement-based treatment. Evidenced-based data exists on the feasibility, implementation, and efficacy of stepped care models in primary care settings for the management of CP and opioid use. Although these studies did not enroll participants with OUD, they included a sub-set of patients at risk for the development of OUD. There remains a dearth of treatment options for those with comorbid CP and OUD. Future research is needed to explore the aetiology and impact of CP and OUD, and greater emphasis is needed to improve access to comprehensive pain and substance use programmes for high-risk individuals.

Double jeopardy: a review of weight gain and weight management strategies for psychotropic medication prescribing during methadone maintenance treatment.

Methadone maintenance treatment (MMT) is an important treatment tool for the opioid epidemic. One challenge is that many persons who present for MMT also have co-occurring psychiatric disorders. Individually, both methadone and psychiatric medications carry risk of weight gain. Therefore, concurrent prescribing of methadone and psychiatric medications places dual diagnosis patients at even greater risk. As a parallel obesity epidemic grows, results from clinical trials assessing weight gain and weight management strategies among MMT and psychiatric patients can both inform and guide clinical practice. This study reviews findings from a literature search for recent clinical trials that focused on weight gain and weight management strategies during MMT with concurrent psychotropic medication use. While several studies have documented weight gain during MMT and psychotropic medication treatment, this study failed to identify recent work that explored concurrent prescribing. Most weight management strategies involved the use of additional medications and available data suggests that MMT and concurrent use of psychotropic medications increases the risk for obesity. More robust research is needed on weight gain and potential mitigation strategies when these treatment modalities are jointly utilized. Clarification of underlying biological mechanisms and development of non-pharmacological interventions merit further consideration.

Sex moderates the effects of positive and negative affect on clinical pain in patients with knee osteoarthritis.

BACKGROUND AND AIMS: Sex differences in clinical pain severity and response to experimental pain are commonly reported, with women generally showing greater vulnerability. Affect, including state (a single rating) and stable (average daily ratings over two weeks) positive affect and negative affect has also been found to impact pain sensitivity and severity, and research suggests that affect may modulate pain differentially as a function of sex. The current study aimed to examine sex as a moderator of the relationships between affect and pain-related outcomes among participants with knee osteoarthritis (KOA). METHODS: One hundred and seventy-nine participants (59 men) with KOA completed electronic diaries assessing clinical pain, positive affect, and negative affect. A subset of participants (n=120) underwent quantitative sensory testing, from which a single index of central sensitization to pain was derived. We used multiple regression models to test for the interactive effects of sex and affect (positive versus negative and stable versus state) on pain-related outcomes. We used mixed effects models to test for the moderating effects of sex on the relationships between state affect and pain over time. RESULTS: Sex differences in affect and pain were identified, with men reporting significantly higher stable positive affect and lower central sensitization to pain indexed by quantitative sensory testing, as well as marginally lower KOA-specific clinical pain compared to women. Moreover, there was an interaction between stable positive affect and sex on KOA-specific clinical pain and average daily non-specific pain ratings. Post hoc analyses revealed that men showed trends towards an inverse relationship between stable positive affect and pain outcomes, while women showed no relationship between positive affect and pain. There was also a significant interaction between sex and stable negative affect and sex on KOA-specific pain such that men showed a significantly stronger positive relationship between stable negative affect and KOA-specific pain than women. Sex did not interact with state affect on pain outcomes. CONCLUSIONS: Findings suggest that men may be particularly sensitive to the effects of stable positive affect and negative affect on clinical pain. Future work with larger samples is needed in order to identify potential mechanisms driving the sex-specific effects of affect on pain. IMPLICATIONS: The current study provides novel data that suggesting that the association of positive affect, negative affect, and pain are different in men versus women with KOA. Further understanding of the difference in affective expression between men and women may lead to the development of novel therapeutic interventions and help to identify additional modifiable factors in the prevention and management of pain.

Characterization of pain, disability, and psychological burden in Marfan syndrome.

The clinical manifestations of Marfan syndrome frequently cause pain. This study aimed to characterize pain in a cohort of adults with Marfan syndrome and investigate demographic, physical, and psychological factors associated with pain and pain-related disability. Two hundred and forty-five participants (73% female, 89% non-Hispanic white, 90% North American) completed an online questionnaire assessing clinical features of Marfan syndrome, pain severity, pain-related disability, physical and mental health, depressive symptoms, pain catastrophizing, and insomnia. Eighty-nine percent of respondents reported having pain with 28% of individuals reporting pain as a presenting symptom of Marfan syndrome. Almost half of individuals reported that pain has spread from its initial site. Participants in our study reported poor physical and mental health functioning, moderate pain-related disability, and mild levels of depressive symptoms, sleep disturbances, and pain catastrophizing. Those who identified pain as an initial symptom of Marfan syndrome and those who reported that pain had spread from its initial site reported greater psychological burden compared with those without pain as an initial symptom or pain spreading. Physical health is the largest predictor of pain severity and pain-related disability. While pain catastrophizing and worse mental health functioning are significant correlates of pain severity and pain-related disability, respectively. Pain is a significant and persistent problem in Marfan syndrome and is associated with profound disability and psychological burden. Further studies are indicated to better characterize the directionality of pain, pain-related disability, and psychological burden in Marfan syndrome. © 2016 Wiley Periodicals, Inc.