Beth D. Darnall

Sex and gender in psychoneuroimmunology research: Past, present and future

To date, research suggests that sex and gender impact pathways central to the foci of psychoneuroimmunology (PNI). This review provides a historical perspective on the evolution of sex and gender in psychoneuroimmunology research. Gender and sexually dimorphic pathways may have synergistic effects on health differences in men and women. We provide an overview of the literature of sex and gender differences in brain structure and function, sex steroids, gender role identification, hypothalamic-pituitary-adrenal axis function, genetics, immunology and cytokine response. Specific examples shed light on the importance of attending to sex and gender methodology in PNI research and recommendations are provided.

Self-Delivered Home-Based Mirror Therapy for Lower Limb Phantom Pain

Home-based patient-delivered mirror therapy is a promising approach in the treatment of phantom limb pain. Previous studies and case reports of mirror therapy have used a therapist-guided, structured protocol of exercises. No case report has described treatment for either upper or lower limb phantom pain by using home-based patient-delivered mirror therapy. The success of this case demonstrates that home-based patient-delivered mirror therapy may be an efficacious, low-cost treatment option that would eliminate many traditional barriers to care.

Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis

Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose. Design Retrospective analysis of claims data, 2001-13. Setting Administrative health claims database. Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid. Interventions Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. Main outcome measures Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose. Results 9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P<0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P<0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16). Conclusions From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.

From Catastrophizing to Recovery: a pilot study of a single-session treatment for pain catastrophizing

Background Pain catastrophizing (PC) – a pattern of negative cognitive-emotional responses to real or anticipated pain – maintains chronic pain and undermines medical treatments. Standard PC treatment involves multiple sessions of cognitive behavioral therapy. To provide efficient treatment, we developed a single-session, 2-hour class that solely treats PC entitled “From Catastrophizing to Recovery” [FCR]. Objectives To determine 1) feasibility of FCR; 2) participant ratings for acceptability, understandability, satisfaction, and likelihood to use the information learned; and 3) preliminary efficacy of FCR for reducing PC. Design and methods Uncontrolled prospective pilot trial with a retrospective chart and database review component. Seventy-six patients receiving care at an outpatient pain clinic (the Stanford Pain Management Center) attended the class as free treatment and 70 attendees completed and returned an anonymous survey immediately post-class. The Pain Catastrophizing Scale (PCS) was administered at class check-in (baseline) and at 2, and 4 weeks post-treatment. Within subjects repeated measures analysis of variance (ANOVA) with Student’s t-test contrasts were used to compare scores across time points. Results All attendees who completed a baseline PCS were included as study participants (N=57; F=82%; mean age =50.2 years); PCS was completed by 46 participants at week 2 and 35 participants at week 4. Participants had significantly reduced PC at both time points (P<0001) and large effect sizes were found (Cohen’s d=0.85 and d=1.15). Conclusion Preliminary data suggest that FCR is an acceptable and effective treatment for PC. Larger, controlled studies of longer duration are needed to determine durability of response, factors contributing to response, and the impact on pain, function and quality of life.

Medical and Psychological Risks and Consequences of Long-Term Opioid Therapy in Women

BACKGROUND Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. PURPOSE To review the medical and psychological risks and consequences of long-term opioid therapy in women. METHOD Scientific literature containing relevant keywords and content were reviewed. RESULTS AND CONCLUSIONS Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted.

Physical and psychological correlates of fatigue and physical function: a Collaborative Health Outcomes Information Registry (CHOIR) study.

UNLABELLED Fatigue is a multidimensional construct that has significant implications for physical function in chronic noncancer pain populations but remains relatively understudied. The current study characterized the independent contributions of self-reported ratings of pain intensity, sleep disturbance, depression, and fatigue to ratings of physical function and pain-related interference in a diverse sample of treatment-seeking individuals with chronic pain. These relationships were examined as a path modeling analysis of self-report scores obtained from 2,487 individuals with chronic pain from a tertiary care outpatient pain clinic. Our analyses revealed unique relationships of pain intensity, sleep disturbance, and depression with self-reported fatigue. Further, fatigue scores accounted for significant proportions of the relationships of both pain intensity and depression with physical function and pain-related interference and accounted for the entirety of the unique statistical relationship between sleep disturbance and both physical function and pain-related interference. Fatigue is a complex construct with relationships to both physical and psychological factors that has significant implications for physical functioning in chronic noncancer pain. The current results identify potential targets for future treatment of fatigue in chronic pain and may provide directions for future clinical and theoretical research in the area of chronic noncancer pain. PERSPECTIVE Fatigue is an important physical and psychological variable that factors prominently in the deleterious consequences of pain intensity, sleep disturbance, and depression for physical function in chronic noncancer pain.

Home-based self-delivered mirror therapy for phantom pain: a pilot study.

OBJECTIVE To test the feasibility and preliminary efficacy of self-delivered home-based mirror therapy for phantom pain. DESIGN Uncontrolled prospective treatment outcome pilot study. PARTICIPANTS Forty community-dwelling adults with unilateral amputation and phantom pain > 3 on a 0-10 numeric rating scale enrolled either during a one-time study visit (n = 30) or remotely (n = 10). METHODS Participants received an explanation of mirror therapy and were asked to self-treat for 25 min daily. Participants completed and posted back sets of outcomes questionnaires at months 1 and 2 post-treatment. Main outcome was average phantom pain intensity at post-treatment. RESULTS A significant reduction in average phantom pain intensity was found at month 1 (n = 31, p = 0.0002) and at month 2 (n = 26, p = 0.002). The overall median percentage reduction at month 2 was 15.4%. Subjects with high education (> 16 years) compared with low education (< 16 years) (37.5% vs 4.1%) had greater reduction in pain intensity (p = 0.01). CONCLUSION These findings support the feasibility and efficacy of home-based self-delivered mirror therapy; this low-cost treatment may defray medical costs, therapy visits, and the patient travel burden for people with motivation and a high level of education. More research is needed to determine methods of cost-effective support for people with lower levels of education.

Pilot study of inflammatory responses following a negative imaginal focus in persons with chronic pain: analysis by sex/gender.

BACKGROUND Recent evidence suggests that differential stress and immune responses may play a role in the sex/gender disparity for pain. Pain pathology and psychological stress are both associated with elevated levels of proinflammatory cytokines. OBJECTIVE This pilot study tested a negative imaginal focus to assess whether it would elicit a proinflammatory cytokine response and whether responses would vary by sex/gender. METHODS Adults with chronic musculoskeletal pain were recruited from an outpatient, multidisciplinary pain clinic in Portland, Oregon, between 2007 and 2008. All participants underwent a psychologist-guided 10-minute focus on the negative aspects of their pain condition and the imagined worsening of their pain; no control group was used. Serum collected at baseline and postfocus (1, 2, and 2.5 hours) was assayed for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Cortisol was assayed at each time point and at 15 minutes postfocus. RESULTS Thirty-six outpatients (aged 26-62 years; 23 women, 13 men) participated in the study. Compared with men, women displayed greater negative emotional expression during the experiment, and this in turn mediated their IL-6 inflammatory responses. Relative to men, the IL-6 response trajectory was delayed for women. The IL-6 and TNF-a findings suggest womens maximal cytokine responses were not captured by the final time point. CONCLUSIONS This pilot study provides preliminary evidence that women with chronic pain may experience increased and delayed inflammatory responses following negative emotional expression induced by thinking negatively about their pain condition. The findings have implications for pain catastrophizing research. This early-phase research suggests that the timing and duration of the cytokine response are critical factors to consider in future pain research.

Contributions of Physical Function and Satisfaction with Social Roles to Emotional Distress in Chronic Pain: A Collaborative Health Outcomes Information Registry (CHOIR) Study

Abstract Individuals with chronic pain show greater vulnerability to depression or anger than those without chronic pain, and also show greater interpersonal difficulties and physical disability. The present study examined data from 675 individuals with chronic pain during their initial visits to a tertiary care pain clinic using assessments from Stanford Universitys Collaborative Health Outcomes Information Registry (CHOIR). Using a path modeling analysis, the mediating roles of Patient-Reported Outcomes Measurement Information Systems (PROMIS) Physical Function and PROMIS Satisfaction with Social Roles and Activities were tested between pain intensity and PROMIS Depression and Anger. Pain intensity significantly predicted both depression and anger, and both physical function and satisfaction with social roles mediated these relationships when modeled in separate 1-mediator models. Notably, however, when modeled together, ratings of satisfaction with social roles mediated the relationship between physical function and both anger and depression. Our results suggest that the process by which chronic pain disrupts emotional well-being involves both physical function and disrupted social functioning. However, the more salient factor in determining pain-related emotional distress seems to be disruption of social relationships, than global physical impairment. These results highlight the particular importance of social factors to pain-related distress, and highlight social functioning as an important target for clinical intervention in chronic pain.

Pain Psychology: A Global Needs Assessment and National Call to Action

Objective. The Institute of Medicine and the draft National Pain Strategy recently called for better training for health care clinicians. This was the first high-level needs assessment for pain psychology services and resources in the United States. Design. Prospective, observational, cross-sectional. Methods. Brief surveys were administered online to six stakeholder groups (psychologists/therapists, individuals with chronic pain, pain physicians, primary care physicians/physician assistants, nurse practitioners, and the directors of graduate and postgraduate psychology training programs). Results. 1,991 responses were received. Results revealed low confidence and low perceived competency to address physical pain among psychologists/therapists, and high levels of interest and need for pain education. We found broad support for pain psychology across stakeholder groups, and global support for a national initiative to increase pain training and competency in U.S. therapists. Among directors of graduate and postgraduate psychology training programs, we found unanimous interest for a no-cost pain psychology curriculum that could be integrated into existing programs. Primary barriers to pain psychology include lack of a system to identify qualified therapists, paucity of therapists with pain training, limited awareness of the psychological treatment modality, and poor insurance coverage. Conclusions. This report calls for transformation within psychology predoctoral and postdoctoral education and training and psychology continuing education to include and emphasize pain and pain management. A system for certification is needed to facilitate quality control and appropriate reimbursement. There is a need for systems to facilitate identification and access to practicing psychologists and therapists skilled in the treatment of pain.