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Chronic pain patients often complain of their poor memory. The mechanisms underlying chronic pain-related memory impairment remain elusive, and there are few clinical therapeutic strategies available for this condition.
Learn More >Chronic pain and opioid use are associated with increased risk for suicidal ideation and behaviors (SIB) in cross-sectional studies, particularly among individuals who catastrophize about their pain. This study examined the longitudinal association between two styles of pain coping, catastrophizing and hoping/praying, as predictors of subsequent SIB, as well as possible mediators of this association among patients with chronic pain receiving long-term opioid therapy. Participants (n = 496) were adults with chronic nonmalignant pain on long-term opioid therapy who did not develop an opioid use disorder. Participants were assessed for pain coping, suicidal ideation, depression, social support and pain interference at baseline, and were reassessed for SI, depression, and pain interference at 6- and 12-month follow-ups. Catastrophizing was a significant predictor of increased subsequent SIB, whereas hoping/praying did not protect against future SIB. The relationship between catastrophizing and future SIB was mediated by depression, but not social support or pain interference. In conclusion, catastrophizing was an important predictor of subsequent SIB due to its effect on increasing depression among patients with chronic nonmalignant pain receiving long-term opioid therapy. Future research should explore the extent to which targeting catastrophizing reduces subsequent depression and suicide risk.
Learn More >Longitudinal Cohort Study OBJECTIVE.: Determine if duration of postoperative opioids is associated with long term outcomes, and if initial postoperative opioid dosage is associated with opioid cessation after spine surgery.
Learn More >Cognitive behavioral therapy (CBT) improves quality of life of patients with irritable bowel syndrome (IBS), a disorder characterized by chronic visceral pain and abnormal bowel habits. Whether CBT can actually improve visceral pain in IBS patients is still unknown. The aim of this study is to evaluate whether environment enrichment (EE), the animal analog of CBT, can prevent stress-induced viscero-somatic hypersensitivity through changes in glucocorticoid receptor (GR) signaling within the central nucleus of the amygdala (CeA).
Learn More >Chronic musculoskeletal pain is a complex medical condition that can significantly impact quality of life. Patients with chronic pain demonstrate attentional biases towards pain-related information. The therapeutic benefits of modifying attentional biases by implicitly training attention away from pain-related information towards neutral information have been supported in a small number of published studies. Limited research however has explored the efficacy of modifying pain-related biases via the internet. This protocol describes a randomised, double-blind, internet-delivered attentional bias modification intervention, aimed to evaluate the efficacy of the intervention on reducing pain interference. Secondary outcomes are pain intensity, state and trait anxiety, depression, pain-related fear, and sleep impairment. This study will also explore the effects of training intensity on these outcomes, along with participants' perceptions about the therapy.
Learn More >Somatosensory neurons have historically been classified by a variety of approaches, including structural, anatomical, and genetic markers; electrophysiological properties; pharmacological sensitivities; and more recently, transcriptional profile differentiation. These methodologies, used separately, have yielded inconsistent classification schemes. Here, we describe phenotypic differences in response to pharmacological agents as measured by changes in cytosolic calcium concentration for the rapid classification of neurons in vitro; further analysis with genetic markers, whole-cell recordings, and single-cell transcriptomics validated these findings in a functional context. Using this general approach, which we refer to as tripartite constellation analysis (TCA), we focused on large-diameter dorsal-root ganglion (L-DRG) neurons with myelinated axons. Divergent responses to the K-channel antagonist, κM-conopeptide RIIIJ (RIIIJ), reliably identified six discrete functional cell classes. In two neuronal subclasses (L1 and L2), block with RIIIJ led to an increase in [Ca] Simultaneous electrophysiology and calcium imaging showed that the RIIIJ-elicited increase in [Ca] corresponded to different patterns of action potentials (APs), a train of APs in L1 neurons, and sporadic firing in L2 neurons. Genetically labeled mice established that L1 neurons are proprioceptors. The single-cell transcriptomes of L1 and L2 neurons showed that L2 neurons are Aδ-low-threshold mechanoreceptors. RIIIJ effects were replicated by application of the K1.1 selective antagonist, Dendrotoxin-K, in several L-DRG subclasses (L1, L2, L3, and L5), suggesting the presence of functional K1.1/K1.2 heteromeric channels. Using this approach on other neuronal subclasses should ultimately accelerate the comprehensive classification and characterization of individual somatosensory neuronal subclasses within a mixed population.
Learn More >Drug-evoked adaptations in the mesolimbic dopamine system are postulated to drive opioid abuse and addiction. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological and behavioral impact. We exposed male and female mice to morphine for one week, with administration patterns that were either intermittent (daily injections) or continuous (osmotic minipump infusion). We then interrupted continuous morphine exposure with either naloxone-precipitated or spontaneous withdrawal. Continuous morphine exposure caused tolerance to the psychomotor-activating effects of morphine, whereas both intermittent and interrupted morphine exposure caused long-lasting psychomotor sensitization. Given links between locomotor sensitization and mesolimbic dopamine signaling, we used fiber photometry and a genetically encoded dopamine sensor to conduct longitudinal measurements of dopamine dynamics in the nucleus accumbens. Locomotor sensitization caused by interrupted morphine exposure was accompanied by enhanced dopamine signaling in the nucleus accumbens. To further assess downstream consequences on striatal gene expression, we used next-generation RNA sequencing to perform genome-wide transcriptional profiling in the nucleus accumbens and dorsal striatum. The interruption of continuous morphine exposure exacerbated drug-evoked transcriptional changes in both nucleus accumbens and dorsal striatum, dramatically increasing differential gene expression and engaging unique signaling pathways. Our study indicates that opioid-evoked adaptations in brain function and behavior are critically dependent on the pattern of drug administration, and exacerbated by interruption of continuous exposure. Maintaining continuity of chronic opioid administration may, therefore, represent a strategy to minimize iatrogenic effects on brain reward circuits.
Learn More >Females are thought to have increased risk of developing post-traumatic headache following a traumatic head injury or concussion. However, the processes underlying this susceptibility remain unclear. We previously demonstrated the development of post-traumatic headache-like pain behaviors in a male rat model of mild closed head injury, along with the ability of sumatriptan and an anti-calcitonin-gene-related peptide monoclonal antibody to ameliorate these behaviors. Here, we conducted a follow-up study to explore the development of post-traumatic headache-like behaviors and the effectiveness of these headache therapies in females subjected to the same head trauma protocol.
Learn More >Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis.
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