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Objective Robust evidence suggests children's catastrophizing about their own pain is a risk factor for poor child pain-related outcomes. In children of parents with chronic pain, child catastrophizing about their parents' pain might be a unique predictor of child pain-related outcomes given their increased exposure to parental chronic pain and disability. The objective of this study was to examine associations between child and parent catastrophizing about their own and each other's pain and child and parent pain-related outcomes. Methods Seventy-two parents with chronic pain and their children (ages 8-15) completed questionnaires assessing their trait catastrophizing about their own and each other's pain, their own pain, and the child's internalizing symptoms. Children completed the cold pressor task (CPT) in the presence of their parent. Parents and children rated children's worst pain intensity and their own anxiety during the task. Analyses were guided by the Actor-Partner Interdependence Model. Results Greater child catastrophizing about parent pain was associated with children's and parents' increased catastrophizing about their own pain. Child catastrophizing about parent pain was associated with greater child- and parent-reported child internalizing symptoms and greater CPT pain intensity for the child, but not parent/child usual pain or CPT anxiety, over and above the influence of parent and child catastrophizing about their own pain. Conclusions Child catastrophizing about parent pain is a potential vulnerability factor associated with poor pain-related outcomes in children of parents with chronic pain that should be considered in future research and clinical settings. Statement of contribution What is already known on this subject? Higher rates of pain and internalizing symptoms are observed in offspring of parents with vs. without chronic pain. Greater child and parent pain catastrophizing are associated with poorer pain-related outcomes in children. Child catastrophizing about parent chronic pain and its association with child outcomes has not been examined. What does this study add? Greater child catastrophizing about parent chronic pain is associated with greater child internalizing and CPT pain. These effects were seen beyond the association of child and parent catastrophizing about their own pain.
Learn More >Glycine neurotransmission in the dorsal horn of the spinal cord plays a key role in regulating nociceptive signaling, but in chronic pain states reduced glycine neurotransmission is associated with the development of allodynia and hypersensitivity to painful stimuli. This suggests that restoration of glycine neurotransmission may be therapeutic for the treatment of chronic pain. Glycine Transporter 2 inhibitors have been demonstrated to enhance glycine neurotransmission and provide relief from allodynia in rodent models of chronic pain. In recent years, photoswitchable compounds have been developed to provide the possibility of controlling the activity of target proteins using light. In this study we have developed a photoswitchable non-competitive inhibitor of Glycine Transporter 2 that has different affinities for the transporter at 365 nm compared to 470 nm light.
Learn More >Voltage-gated sodium (Nav) channels respond to changes in the membrane potential of excitable cells through the concerted action of four voltage-sensor domains (VSDs). Subtype Nav1.7 plays an important role in the propagation of signals in pain-sensing neurons and is a target for the clinical development of novel analgesics. Certain inhibitory cystine knot (ICK) peptides produced by venomous animals potently modulate Nav1.7; however, the molecular mechanisms underlying their selective binding and activity remain elusive. This study reports on the design of a library of photoprobes based on the potent spider toxin Huwentoxin-IV and the determination of the toxin binding interface on VSD2 of Nav1.7 through a photocrosslinking and tandem mass spectrometry approach. Our Huwentoxin-IV probes selectively crosslink to extracellular loop S1-S2 and helix S3 of VSD2 in a chimeric channel system. Our results provide a strategy that will enable mapping of sites of interaction of other ICK peptides on Nav channels.
Learn More >Chronic radicular neuropathic pain is a major clinical problem with a life time prevalence of more than 50%. Pulsed radiofrequency (PRF) treatment is a recognised therapy. However, the pathophysiology of chronic neuropathic pain (CNP) and the mechanism of action of PRF remains ill-defined. Improving our knowledge of the mechanisms of CNP and PRF action will enhance our ability to treat patients with this common debilitating problem more effectively. This study aims to characterise the CSF cellular and peptide constituents in patients with CNP and the effect of pulsed radiofrequency (PRF) on these constituents and reported pain.
Learn More >Registry based repeated-measures psychometric validation of the Danish Oswestry Disability Index (ODI) OBJECTIVE.: The goal was to use classical and modern psychometric validation methods to assess the measurement properties and the minimally clinical important difference (MCID) of the ODI in a Danish cohort of patients with chronic low back pain (LBP) being treated with spinal surgery.
Learn More >Paclitaxel-induced neuropathic pain (PINP) is refractory to currently used analgesics. Previous studies show a pivotal role of oxidative stress in PINP. Because the nuclear factor erythroid-2-related factor 2 (Nrf2) has been considered as the critical regulator of endogenous antioxidant defense, we here explored whether activation of Nrf2 could attenuate PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to assess mechanical allodynia. We showed that a single dose of Nrf2 activator, oltipraz (10, 50, and 100 mg/kg), dose-dependently attenuated established mechanical allodynia, whereas repeated injection of oltipraz (100 mg· kg· d, i.p. from d 14 to d 18) almost abolished the mechanical allodynia in PINP rats. The antinociceptive effect of oltipraz was blocked by pre-injection of Nrf2 inhibitor trigonelline (20 mg/kg, i.p.). Early treatment with oltipraz (100 mg· kg· d, i.p. from d 0 to d 6) failed to prevent the development of the PINP, but delayed its onset. Western blot and immunofluorescence analysis revealed that the expression levels of Nrf2 and HO-1 were significantly upregulated in the spinal cord of PINP rats. Repeated injection of oltipraz caused further elevation of the expression levels of Nrf2 and HO-1 in the spinal cord of PINP rats, which was reversed by pre-injection of trigonelline. These results demonstrate that oltipraz ameliorates PINP via activating Nrf2/HO-1-signaling pathway in the spinal cord.
Learn More >The growing presence of artificial lighting across the globe presents a number of challenges to human and ecological health despite its societal benefits. Exposure to artificial light at night, a seemingly innocuous aspect of modern life, disrupts behavior and physiological functions. Specifically, light at night induces neuroinflammation, which is implicated in neuropathic and nociceptive pain states, including hyperalgesia and allodynia. Because of its influence on neuroinflammation, we investigated the effects of dim light at night exposure on pain responsiveness in male mice. In this study, mice exposed to four days of dim (5 lux) light at night exhibited cold hyperalgesia. Further, after 28 days of exposure, mice exhibited both cold hyperalgesia and mechanical allodynia. No heat/hot hyperalgesia was observed in this experiment. Altered nociception in mice exposed to dim light at night was concurrent with upregulated interleukin-6 and nerve growth factor mRNA expression in the medulla and elevated μ-opioid receptor mRNA expression in the periaqueductal gray region of the brain. The current results support the relationship between disrupted circadian rhythms and altered pain sensitivity. In summary, we observed that dim light at night induces cold hyperalgesia and mechanical allodynia, potentially through elevated central neuroinflammation and dysregulation of the endogenous opioid system.
Learn More >Biological sex influences inflammatory response, as there is a greater incidence of acute inflammation in men and chronic inflammation in women. Here, we report that acute inflammation is attenuated by X-inactive specific transcript (Xist), a female cell-specific nuclear long noncoding RNA crucial for X-chromosome inactivation. Lipopolysaccharide-mediated acute inflammation increased Xist levels in the cytoplasm of female mouse J774A.1 macrophages and human AML193 monocytes. In both cell types, cytoplasmic Xist colocalizes with the p65 subunit of NF-κB. This interaction was associated with reduced NF-κB nuclear migration, suggesting a novel mechanism to suppress acute inflammation. Further supporting this hypothesis, expression of 5' XIST in male cells significantly reduced IL-6 and NF-κB activity. Adoptive transfer of male splenocytes expressing Xist reduced acute paw swelling in male mice indicating that Xist can have a protective anti-inflammatory effect. These findings show that XIST has functions beyond X chromosome inactivation and suggest that XIST can contribute to sex-specific differences underlying inflammatory response by attenuating acute inflammation in women.
Learn More >Background and aims A sizable body of research has elucidated the significant role of psychological reactions to trauma on pain coping and outcomes. In order to best inform intervention development and clinical care for patients with both trauma and pain at the tertiary care level, greater clarity is needed regarding the magnitude of these effects and the specific pathways through which they may or may not function at the time of first presentation to such a treatment setting. To achieve this, the current study examined the cross-sectional relationships between traumatic etiology of pain, psychological distress (anger, depressive symptoms, and PTSD symptoms), and pain outcomes (pain catastrophizing, physical function, disability status). Methods Using a structural path modeling approach, analyses were conducted using a large sample of individuals with chronic pain (n = 637) seeking new medical evaluation at a tertiary pain management center, using the Collaborative Health Outcomes Information Registry (CHOIR). We hypothesized that the relationships between traumatic etiology of pain and poorer pain outcomes would be mediated by higher levels of psychological distress. Results Our analyses revealed modest relationships between self-reported traumatic etiology of pain and pain catastrophizing, physical function, and disability status. In comparison, there were stronger relationships between indices of psychological distress and pain catastrophizing, but a weaker pattern of associations between psychological distress and physical function and disability measures. Conclusions To the relatively small extent that self-reported traumatic etiology of pain correlates with pain-related outcomes, these relationships appear to be due primarily to the presence of psychiatric symptoms and manifest most notably in the context of psychological responses to pain (i.e. catastrophizing about pain). Implications Findings from this study highlight the need for early intervention for patients with traumatic onset of pain and for clinicians at tertiary pain centers to include more detailed assessments of psychological distress and trauma as a component of comprehensive chronic pain treatment.
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