The Association Between Perceived Injustice and Opioid Craving in Patients With Chronic Pain: The Mediating Role of Daily Pain Intensity, Negative Affect, and Catastrophizing.

OBJECTIVES: The first objective of this study was to examine the association between perceived injustice and opioid craving in patients with chronic pain who are prescribed opioids. We also examined whether pain intensity, negative affect, or catastrophizing mediated this association. METHODS: In this longitudinal diary study, patients (n = 103) completed a questionnaire assessing perceived injustice and then completed daily measures of pain intensity, negative affect, catastrophizing, and opioid craving for 14 consecutive days. RESULTS: A significant association was found between perceived injustice and opioid craving ( P < 0.01), with higher levels of perceived injustice being associated with heightened levels of opioid craving. A 2-1-1 multilevel mediation analysis indicated that the association between perceived injustice and craving was significantly mediated by catastrophizing ( P < 0.05). CONCLUSIONS: The present study provides new insights into the factors that might contribute to opioid craving in patients with chronic pain. Our findings suggest that perceived injustice might lead to increased catastrophizing and, in turn, heightened daily levels of opioid craving. These findings could have implications for chronic pain management clinicians who prescribe opioids.

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia.

ABSTRACT: The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.

Day-to-day opioid withdrawal symptoms, psychological distress, and opioid craving in patients with chronic pain prescribed opioid therapy.

BACKGROUND: Research has shown that opioid craving is one of the strongest determinants of opioid misuse in patients with chronic pain. To date, however, little is known on the factors that contribute to opioid craving in these patients. It is possible that patients' physical dependence to opioids, manifested by opioid withdrawal symptoms in between daily opioid doses, contribute to opioid craving. Physical dependence symptoms might also lead to psychological distress, which in turn might contribute to opioid craving. The first objective of this study was to examine the day-to-day association between opioid withdrawal symptoms and opioid craving among patients with chronic pain. We also examined whether negative affect and catastrophic thinking mediated this association. METHODS: In this longitudinal study, chronic pain patients (n = 79) prescribed short-acting opioids completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables. RESULTS: Day-to-day elevations in opioid withdrawal symptoms were associated with heightened opioid craving (p < .001). Results of a multilevel mediation analysis revealed that this association was mediated by patients' daily levels of negative affect and catastrophizing (p < .001). CONCLUSIONS: Our study provides valuable new insights into our understanding of factors that may contribute to prescription opioid craving among patients with chronic pain.

Day-to-day hedonic and calming effects of opioids, opioid craving, and opioid misuse among patients with chronic pain prescribed long-term opioid therapy.

ABSTRACT: Concerns have been raised regarding the misuse of opioids among patients with chronic pain. Although a number of factors may contribute to opioid misuse, research has yet to examine if the hedonic and calming effects that can potentially accompany the use of opioids contribute to opioid misuse. The first objective of this study was to examine the degree to which the hedonic and calming effects of opioids contribute to opioid misuse in patients with chronic pain. We also examined whether the hedonic and calming effects of opioids contribute to patients' daily levels of opioid craving, and whether these associations were moderated by patients' daily levels of pain intensity, catastrophizing, negative affect, or positive affect. In this longitudinal diary study, patients (n = 103) prescribed opioid therapy completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables. The hedonic and calming effects of opioids were not significantly associated with any type of opioid misuse behavior. However, greater hedonic and calming effects were associated with heightened reports of opioid craving (both P's < 0.005). Analyses revealed that these associations were moderated by patients' daily levels of pain intensity, catastrophizing, and negative affect (all P's < 0.001). Results from this study provide valuable new insights into our understanding of factors that may contribute to opioid craving among patients with chronic pain who are prescribed long-term opioid therapy. The implications of our findings for the management of patients with chronic pain are discussed.