Erik Schuster

Temporal associations between spouse criticism/hostility and pain among patients with chronic pain: a within-couple daily diary study.

Summary In this within‐couple diary study of patients with chronic low back pain and their spouses, we found that patient perceived criticism/hostility from their spouse was related to patient pain concurrently, and that spouse observations of patient pain behaviors predicted patient perceived hostility in the next 3 hour period. Spouse criticism and hostility directed toward patients may adversely affect the latter’s well‐being. Abstract Chronic musculoskeletal pain can strain marriages, perhaps even to the point of engendering spouse criticism and hostility directed toward patients. Such negative spouse responses may have detrimental effects on patient well‐being. While results of cross‐sectional studies support this notion, we extended these efforts by introducing expressed emotion (EE) and interpersonal theoretical perspectives, and by using electronic diary methods to capture both patient and spouse reports in a prospective design. Patients with chronic low back pain (CLBP) and their spouses (N = 105 couples) reported on perceived spouse behavior and patient pain 5 times/day for 14 days using Personal Data Assistants (PDAs). Concurrent and lagged within‐couple associations between patient’s perceptions of spouse criticism/hostility and patient self‐reported pain and spouses’ observations of patient pain behaviors revealed that (1) patient perceived spouse criticism and hostility were correlated significantly with pain intensity, and spouse observed patient pain behavior was related significantly with patient perceived hostility at the same time point; (2) patient perceived spouse hostility significantly predicted patient pain intensity 3 hours later, and spouse observed pain behaviors significantly predicted patient perceived spouse hostility 3 hours later. Results support both EE and interpersonal models, and imply that a comprehensive model would combine these conceptualizations to fully illustrate how spouse criticism/hostility and patient pain interact to produce a negative spiral. Given that marital interactions are amenable to clinical intervention, improved insight into how spouse behavior and patient pain are tightly linked will encourage productive translational efforts to target this neglected area.

Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses

Summary Individual differences in endogenous opioid function predict morphine analgesic responses, and these endogenous opioid differences mediate the association between greater laboratory‐evoked pain sensitivity and greater analgesic responses to morphine. ABSTRACT Predictors of responsiveness to opioid analgesic medications are not well understood. This study tested whether individual differences in endogenous opioid (EO) function are associated with analgesic responsiveness to morphine. In randomized, counterbalanced order over 3 sessions, 45 chronic low back pain participants and 31 healthy controls received an opioid antagonist (8 mg naloxone), morphine (0.08 mg/kg), or placebo. Participants then engaged in 2 laboratory‐evoked pain tasks (ischemic and thermal). Outcomes included pain threshold, pain tolerance, and pain ratings. Indexes of EO function and morphine analgesic responsiveness were derived for each measure as the difference in pain responses between the placebo condition and naloxone or morphine condition, respectively. For all 7 pain measures across the 2 laboratory pain tasks, greater EO function was associated with significantly lower morphine analgesic responsiveness (P < 0.001–P = 0.02). Morphine reduced pain responses of low EO individuals to levels similar to those of high EO individuals receiving placebo. Higher placebo condition–evoked pain sensitivity was associated with significantly greater morphine analgesic responsiveness for 5 of 7 pain measures (P < 0.001–P = 0.02). These latter associations were significantly mediated by EO function for 4 of these 5 pain outcomes (all P values < 0.05). In the laboratory‐evoked pain context, opioid analgesic medications may supplement inadequate EO analgesia, with little incremental benefit in those with preexisting high EO function. Implications for personalized medicine are discussed.

Anger arousal and behavioral anger regulation in everyday life among patients with chronic low back pain: Relationships to patient pain and function.

OBJECTIVE The objective of this study was to determine the degree to which patient anger arousal and behavioral anger regulation (expression, inhibition) occurring in the course of daily life was related to patient pain and function as rated by patients and their spouses. METHOD Married couples (N = 105) (one spouse with chronic low back pain) completed electronic daily diaries, with assessments 5 times/day for 14 days. Patients completed items on their own state anger, behavioral anger expression and inhibition, and pain-related factors. Spouses completed items on their observations of patient pain-related factors. Hierarchical linear modeling was used to test concurrent and lagged relationships. RESULTS Patient-reported increases in state anger were related to their reports of concurrent increases in pain and pain interference and to spouse reports of patient pain and pain behavior. Patient-reported increases in behavioral anger expression were related to lagged increases in pain intensity and interference and decreases in function. Most of these relationships remained significant with state anger controlled. Patient-reported increases in behavioral anger inhibition were related to concurrent increases in pain interference and decreases in function, which also remained significant with state anger controlled. Patient-reported increases in state anger were related to lagged increases in spouse reports of patient pain intensity and pain behaviors. CONCLUSIONS Results indicate that in patients with chronic pain, anger arousal and behavioral anger expression and inhibition in everyday life are related to elevated pain intensity and decreased function as reported by patients. Spouse ratings show some degree of concordance with patient reports.

Endogenous opioid inhibition of chronic low-back pain influences degree of back pain relief after morphine administration.

Background and Objectives Factors underlying differential responsiveness to opioid analgesic medications used in chronic pain management are poorly understood. We tested whether individual differences in endogenous opioid inhibition of chronic low-back pain were associated with the magnitude of acute reductions in back pain ratings after morphine administration. Methods In randomized counterbalanced order over three sessions, 50 chronic low-back pain patients received intravenous naloxone (8 mg), morphine (0.08 mg/kg), or placebo. Back pain intensity was rated predrug and again after peak drug activity was achieved using the McGill Pain Questionnaire–Short Form (Sensory and Affective subscales, VAS Intensity measure). Opioid blockade effect measures to index degree of endogenous opioid inhibition of back pain intensity were derived as the difference between predrug to postdrug changes in pain intensity across placebo and naloxone conditions, with similar morphine responsiveness measures derived across placebo and morphine conditions. Results Morphine significantly reduced back pain compared with placebo (McGill Pain Questionnaire–Short Form Sensory, VAS; P < 0.01). There were no overall effects of opioid blockade on back pain intensity. However, individual differences in opioid blockade effects were significantly associated with the degree of acute morphine-related reductions in back pain on all measures, even after controlling for effects of age, sex, and chronic pain duration (P < 0.03). Individuals exhibiting greater endogenous opioid inhibition of chronic back pain intensity reported less acute relief of back pain with morphine. Conclusions Morphine appears to provide better acute relief of chronic back pain in individuals with lower natural opioidergic inhibition of chronic pain intensity. Possible implications for personalized medicine are discussed.

Anger arousal and behavioral anger regulation in everyday life among people with chronic low back pain: Relationships with spouse responses and negative affect.

OBJECTIVE To determine the degree to which anger arousal and anger regulation (expression, inhibition) in the daily lives of people with chronic pain were related to spouse support, criticism, and hostility as perceived by patients and as reported by spouses. METHOD Married couples (N = 105, 1 spouse with chronic low back pain) completed electronic daily diaries, with assessments 5 times/day for 14 days. On these diaries, patients completed items on their own anger arousal, anger expression, and inhibition, and on perceived spouse support, criticism, and hostility. Spouses reported on their responses toward patients and their negative affect. Hierarchical linear modeling tested concurrent and lagged relationships. RESULTS Patient-reported increases in anger arousal and anger expression were predominantly related to concurrent decreases in patient-perceived and spouse-reported spouse support, concurrent increases in patient-perceived and spouse-reported spouse criticism and hostility, and increases in spouse-reported negative affect. Relationships for anger expression remained significant with anger arousal controlled. These effects were especially strong for male patients. Spouses reported greater negative affect when patients were present than when they were not. CONCLUSIONS Social support may facilitate adjustment to chronic pain, with declining support and overt criticism and hostility possibly adversely impacting pain and function. Results suggest that patient anger arousal and expression may be related to a negative interpersonal environment for married couples coping with chronic low back pain.

The Contribution of Differential Opioid Responsiveness to Identification of Opioid Risk in Chronic Pain Patients

UNLABELLED The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) predicts increased risk of opioid misuse in chronic pain patients. We evaluated whether higher SOAPP-R scores are associated with greater opioid reinforcing properties, potentially contributing to their predictive utility. Across 2 counterbalanced laboratory sessions, 55 chronic low back pain sufferers completed the SOAPP-R at baseline and measures of back pain intensity, evoked pain responsiveness (thermal, ischemic), and subjective opioid effects after receiving intravenous morphine (.08 mg/kg) or saline placebo. Morphine effect measures were derived for all outcomes, reflecting the difference between morphine and placebo condition values. Higher SOAPP-R scores were significantly associated with greater desire to take morphine again, less feeling down and feeling bad, and greater reductions in sensory low back pain intensity following morphine administration. This latter effect was due primarily to SOAPP-R content assessing medication-specific attitudes and behavior. Individuals exceeding the clinical cutoff (18 or higher) on the SOAPP-R exhibited significantly greater morphine liking, desire to take morphine again, and feeling sedated; less feeling bad; and greater reductions in sensory low back pain following morphine. The SOAPP-R may predict elevated opioid risk in part by tapping into individual differences in opioid reinforcing effects. PERSPECTIVE Based on placebo-controlled morphine responses, associations were observed between higher scores on a common opioid risk screener (SOAPP-R) and greater desire to take morphine again, fewer negative subjective morphine effects, and greater analgesia. Opioids may provide the best analgesia in those patients at greatest risk of opioid misuse.

Expectancy Effects on Conditioned Pain Modulation Are Not Influenced by Naloxone or Morphine

BackgroundRecent studies suggest that participant expectations influence pain ratings during conditioned pain modulation testing. The present study extends this work by examining expectancy effects among individuals with and without chronic back pain after administration of placebo, naloxone, or morphine.PurposeThis study aims to identify the influence of individual differences in expectancy on changes in heat pain ratings obtained before, during, and after a forearm ischemic pain stimulus.MethodsParticipants with chronic low back pain (n = 88) and healthy controls (n = 100) rated heat pain experience (i.e., “test stimulus”) before, during, and after exposure to ischemic pain (i.e., “conditioning stimulus”). Prior to testing, participants indicated whether they anticipated that their heat pain would increase, decrease, or remain unchanged during ischemic pain.ResultsAnalysis of the effects of expectancy (pain increase, decrease, or no change), drug (placebo, naloxone, or morphine), and group (back pain, healthy) on changes in heat pain revealed a significant main effect of expectancy (p = 0.001), but no other significant main effects or interactions. Follow-up analyses revealed that individuals who expected lower pain during ischemia reported significantly larger decreases in heat pain as compared with those who expected either no change (p = 0.004) or increased pain (p = 0.001).ConclusionsThe present findings confirm that expectancy is an important contributor to conditioned pain modulation effects, and therefore significant caution is needed when interpreting findings that do not account for this individual difference. Opioid mechanisms do not appear to be involved in these expectancy effects.

Relationship between endogenous opioid function and opioid analgesic adverse effects.

Background and Objectives Our recent work indicates that endogenous opioid activity influences analgesic responses to opioid medications. This secondary analysis evaluated whether endogenous opioid activity is associated with degree of opioid analgesic adverse effects, and whether chronic pain status and sex affect these adverse effects. Methods Using a double-blind, randomized, placebo-controlled, crossover design, 51 subjects with chronic low back pain and 38 healthy controls participated in 3 separate sessions, undergoing 2 laboratory-evoked pain tasks (ischemic and thermal) after receiving placebo, naloxone, or morphine. Endogenous opioid system function was indexed by the difference in pain responses between the placebo and naloxone conditions. These measures were examined for associations with morphine-related adverse effects. Results Chronic pain subjects reported significantly greater itching and unpleasant bodily sensations with morphine than controls (P < 0.05). Across groups, only 6 of 112 possible associations between adverse effects and blockade effects were significant. For the ischemic task, higher endogenous opioid function was associated with greater itching (visual analog scale [VAS]; P < 0.05), numbness (tolerance; P < 0.001), dry mouth (tolerance; P < 0.05), and unpleasant bodily sensations (VAS; P < 0.05). For the thermal task, higher endogenous opioid function was associated with greater numbness (VAS; P < 0.05) and feeling carefree (VAS; P < 0.05). There were no significant main or interaction effects of chronic pain status or sex on these findings. Conclusions No consistent relationships were observed between endogenous opioid function and morphine-related adverse effects. This is in stark contrast to our previous observation of strong relationships between elevated endogenous opioid function and smaller morphine analgesic effects.

Psychosocial factors predict opioid analgesia through endogenous opioid function

Abstract Use of opioid analgesics for management of chronic nonmalignant pain has become common, yet there are presently no well-validated predictors of optimal opioid analgesic efficacy. We examined whether psychosocial factors (eg, depressive symptoms) predicted changes in spontaneous low back pain after administration of opioid analgesics, and whether endogenous opioid (EO) function mediated these relationships. Participants with chronic low back pain but who were not chronic opioid users (N = 89) underwent assessment of low back pain intensity pre- and post-drug in 3 (counterbalanced) conditions: (1) placebo, (2) intravenous naloxone, and (3) intravenous morphine. Comparison of placebo condition changes in back pain intensity to those under naloxone and morphine provided indexes of EO function and opioid analgesic responses, respectively. Results showed that (1) most psychosocial variables were related significantly and positively to morphine analgesic responses for low back pain, (2) depressive symptoms, trait anxiety, pain catastrophizing, and pain disability were related negatively to EO function, and (3) EO function was related negatively to morphine analgesic responses for low back pain. Bootstrapped mediation analyses showed that links between morphine analgesic responses and depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability were partially mediated by EO function. Results suggest that psychosocial factors predict elevated analgesic responses to opioid-based medications, and may serve as markers to identify individuals who benefit most from opioid therapy. Results also suggest that people with greater depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability may have deficits in EO function, which may predict enhanced response to opioid analgesics.

Do Resting Plasma β-Endorphin Levels Predict Responses to Opioid Analgesics?

Objectives: Clinically feasible predictors of opioid analgesic responses for use in precision pain medicine protocols are needed. This study evaluated whether resting plasma &bgr;-endorphin (BE) levels predicted responses to an opioid analgesic, and whether chronic pain status or sex moderated these effects. Methods: Participants included 73 individuals with chronic low back pain (CLBP) and 88 pain-free controls, all using no daily opioid analgesics. Participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo, with blood samples obtained before drug administration to assay resting plasma BE levels. Once peak drug activity was achieved in each session, participants engaged in an ischemic forearm pain task (ISC) and a heat pain task. Morphine analgesic effects were derived reflecting the difference in pain outcomes between placebo and morphine conditions. Results: In hierarchical regressions, significant Type (CLBP vs. control)×BE interactions (Ps<0.05) were noted for morphine effects on ISC tolerance, ISC intratask pain ratings, and thermal VAS unpleasantness ratings. These interactions derived primarily from associations between higher BE levels and smaller morphine effects restricted to the CLBP subgroup. All other BE-related effects, including sex interactions, for predicting morphine analgesia failed to reach statistical significance. Discussion: BE was a predictor of morphine analgesia for only 3 out of 9 outcomes examined, with these effects moderated by chronic pain status but not sex. On the whole, results do not suggest that resting plasma BE levels are likely to be a clinically useful predictor of opioid analgesic responses.