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Patients qualifying for Medicare disability have the highest rates of opioid use compared with older Medicare beneficiaries and commercial insurance beneficiaries. Research on opioid overdose deaths in this population can help identify appropriate interventions.
Individuals with chronic pain commonly report significant functional impairment and reduced quality of life. Despite this, little is known about psychological processes and mechanisms underpinning enhancements in well-being within this population. The study aimed to investigate whether (1) increased levels of pain intensity and interference were associated with lower levels of mental well-being, (2) increased positive goal engagement was associated with higher levels of mental well-being and (3) whether the relationships between pain characteristics and mental well-being were mediated by increased positive goal engagement. A total of 586 individuals with chronic pain participated in the cross-sectional, online study. Participants completed self-report measures to assess pain intensity and interference, mental well-being and goal motivation variables. Results showed that pain interference and positive goal engagement were associated with mental well-being. Moreover, the relationship between pain interference and mental well-being was partially mediated by positive goal engagement. The results provide tentative evidence for the protective role of positive goal engagement in enabling individuals with chronic pain to maintain a sense of mental well-being. The study develops the biopsychosocial model of chronic pain by examining the roles and relationships of relevant yet previously unexplored psychological constructs. The promotion of mental well-being through the enhancement of positive goal engagement is discussed, offering a platform for further research and clinical interventions.
Bone cancer pain (BCP), which is induced by primary or metastatic bone cancer, remains a clinically challenging problem due to the poor understanding of its mechanisms. Sirtuin 1 (SIRT1) plays an important role in various pain models. Intrathecal administration of SRT1720, a SIRT1 activator, attenuates BCP in a rat model. However, the expression and activity of SIRT1 during the development and maintenance of BCP remain unknown. Furthermore, the underlying mechanism of SIRT1 in BCP remains ambiguous. In this study, we detected the time course of SIRT1 expression and activity in the spinal cord of mice with BCP and examined whether SRT1720 alleviated BCP by inhibiting metabotropic glutamatergic receptor (mGluR) 1/5 expression. In addition, we downregulated spinal SIRT1 expression in normal mice through an intrathecal injection of AAV-SIRT1-shRNA and then assessed pain behavior and mGluR1/5 expression. Mice with BCP developed significant mechanical allodynia and spontaneous flinching, accompanied by decreased levels of the SIRT1 protein, mRNA, and activity in the spinal cord. The SRT1720 treatment produced an analgesic effect on tumor-bearing mice and decreased the spinal levels of the mGluR1/5 protein and mRNA. In contrast, the AAV-SIRT1-shRNA treatment induced pain behavior in normal mice and increased the spinal levels of the mGluR1/5 protein and mRNA. The results suggested a critical role for SIRT1 in the development and maintenance of BCP and further indicated that activation of SIRT1 in the spinal cord by SRT1720 functionally reverses BCP in mice by inhibiting mGluR1/5.
Comorbid psychiatric and pain-related conditions are common in patients with fibromyalgia. Most studies in this area have used data from patients in specialty care and may not represent the characteristics of fibromyalgia in primary care patients. We sought to fill gaps in the literature by determining if the association between psychiatric diagnoses, conditions associated with chronic pain, and fibromyalgia differed by gender in a primary care patient population.
Attachment influences the way individuals anticipate, react, and seek support when faced with chronic pain. Although cross-sectional research indicates that attachment insecurity and pain self-efficacy are associated with pain intensity in chronic pain populations, little is known about their long-term effects on pain, and about the directionality of associations between these constructs. Furthermore, whereas attachment is a relational concept, few studies on genito-pelvic pain have espoused a couples' perspective.
To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention.
The search for new ligands to treat neuropathic pain remains a challenge. Recently, oxytocin has emerged as an interesting molecule modulating nociception at central and peripheral levels, but no attempt has been made to evaluate the effect of recurrent oxytocin administration in neuropathic pain. Using male Wistar rats with spinal nerve ligation, we evaluated the effects of recurrent spinal (1 nmol; given by lumbar puncture) or peripheral (31 nmol; given by intraplantar injection in the ipsilateral paw to spinal nerve ligation) oxytocin administration on pain-like behavior in several nociceptive tests (tactile allodynia and thermal and mechanical hyperalgesia) on different days. Furthermore, we used an electrophysiological approach to analyze the effect of spinal 1 nmol oxytocin on the activity of spinal dorsal horn wide dynamic range cells. In neuropathic rats, spinal or peripheral oxytocin partially restored the nociceptive threshold measured with the von Frey filaments (tactile allodynia), Hargreaves (thermal hyperalgesia) and Randall-Selitto (mechanical hyperalgesia) tests for 12 days. These results agree with electrophysiological data showing that spinal oxytocin diminishes the neuronal firing of the WDR neurons evoked by peripheral stimulation. This effect was associated with a decline in the activity of primary afferent Aδ- and C-fibers. The above findings show that repeated spinal or peripheral oxytocin administration attenuates the pain-like behavior in a well-established model of neuropathic pain. This study provides a basis for addressing the therapeutic relevance of oxytocin in chronic pain conditions.
Cannabinoid receptors type 1 (CB) and type 2 (CB) are promising targets for a number of diseases, including obesity, neuropathic pain, and multiple sclerosis, among others. Upon ligand-mediated activation of these receptors, multiple receptor conformations could be stabilized, resulting in a complex pattern of possible intracellular effects. Although numerous compounds have been developed and widely used to target cannabinoid receptors, their mode of action and signaling properties are often only poorly characterized. From a drug development point of view, unraveling the underlying complex signaling mechanism could offer the possibility to generate medicines with the desired therapeutic profile. Recently, an increased interest has emerged for the development of agonists that are signaling pathway-selective and thereby do not evoke on-target adverse effects. This phenomenon, in which specific pathways are preferred upon receptor activation by certain ligands, is also known as 'biased signaling'. For a particular group of cannabinoid receptor ligands (i.e. CB/CB agonists), namely the synthetic cannabinoid receptor agonists (SCRAs), the research on biased signaling is still in its infancy and interesting outcomes are only recently being revealed. Therefore, this review aims at providing insights into the recent knowledge about biased agonism mediated by SCRAs so far. In addition, as these outcomes are obtained using a distinct panel of functional assays, the accompanying difficulties and challenges when comparing functional outcomes are critically discussed. Finally, some guidance on the conceptualization of ideal in vitro assays for the detection of SCRA-mediated biased agonism, which is also relevant for compounds belonging to other chemical classes, is provided.
This study aimed to identify relationships between sensory function and pain in common pain conditions (Arthritis, Complex Regional Pain Syndrome (CRPS) and Fibromyalgia Syndrome (FMS)) and healthy participants. Sensory abnormalities are known to be concomitant with some types of chronic pain but comparison across pain conditions using existing research is difficult due to methodological differences. Pragmatic Quantitative Sensory Testing (QST) methods were used.