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Opioids and NSAIDs are commonly used for pain relief in AP. Opioids carry risk of sphincter of oddi constriction. Although diclofenac prevents post ERCP pancreatitis, few reports of diclofenac associated AP is also present. Although, both tramadol and diclofenac are commonly used for pain relief in AP, no study has evaluated their comparative efficacy and safety.
Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low-dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, six and 12 months after major lower back surgery.
Complex regional pain syndrome (CRPS) develops after limb injury, with persistent pain and deficits in movement frequently co-occurring. The striatum is critical for mediating multiple mechanisms that are often aberrant in CRPS, which includes sensory and pain processing, motor function and goal-directed behaviors associated with movement. Yet much remains unknown with regards to the morphological and functional properties of the striatum and its sub-regions in this disease. Thus, we investigated 20, patients (15 female, age 58 ± 9 years, right-handed) diagnosed with chronic (6+ months of pain duration) CRPS in the right hand and 20 matched, healthy controls with anatomical and resting-state, functional magnetic resonance imaging (fMRI). In addition, a comprehensive clinical and behavioral evaluation was performed, where each participant's pain, motor function and medical history were assessed. CRPS patients harbored significant abnormalities in hand coordination, dexterity and strength. These clinical pain and movement-related findings in CRPS patients were concomitant with bilateral decreases in gray matter density in the putamen as well as functional connectivity increases and decreases amongst the putamen and pre-/postcentral gyri and cerebellum, respectively. Importantly, higher levels of clinical pain and motor impairment were associated with increased putamen-pre-/postcentral gyri functional connectivity strengths. Collectively, these findings suggest that putaminal alterations, specifically the functional interactions with sensorimotor structures, may underpin clinical pain and motor impairment in chronic CRPS patients.
Neurogenic inflammation, mediated by the activation of primary neurons, is thought to be an important factor in migraine pathophysiology. Programmed cell death ligand-1 (PD-L1) can suppress the immune response through the Programmed cell death-1 receptor. However, the role of PD-L1/PD-1 in migraine remains unclear. In this study we evaluated the expression and role of PD-L1/PD-1 in the trigeminal ganglia in an animal model of acute migraine.
Radiating pain is a significant feature of chronic musculoskeletal pain conditions such as radiculopathies, repetitive motion disorders and whiplash associated disorders. It is reported to be caused by the development of mechanically-sensitive ectopic receptive fields along intact nociceptor axons at sites of peripheral neuroinflammation (neuritis). Since inflammation disrupts axonal transport, we have hypothesised that anterogradely-transported mechanically sensitive ion channels accumulate at the site of disruption, which leads to axonal mechanical sensitivity (AMS). In this study, we have characterised the mechanical properties of the ectopic axonal receptive fields and have examined the contribution of mechanically sensitive ion channels to the development of AMS following neuritis and vinblastine-induced axonal transport disruption. In both models, there was a positive force-discharge relationship and mechanical thresholds were low (∼9 mN/mm). All responses were attenuated by ruthenium red and FM1-43, which block mechanically sensitive ion channels. In both models, the transport of TRPV1 and TRPA1 was disrupted, and intraneural injection of agonists of these channels caused responses in neurons with AMS following neuritis but not vinblastine treatment. In summary, these data support a role for mechanically sensitive ion channels in the development of AMS.
The effective management of pain is a longstanding public health concern. Although opioids have been frontline analgesics for decades, they also have well-known undesirable effects that limit their clinical utility, such as abuse liability and respiratory depression. The failure to develop better analgesics has, in some ways, contributed to the escalating opioid epidemic that has claimed tens of thousands of lives and has cost hundreds of billions of dollars in health-care expenses. A paradigm shift is needed in the pharmacotherapy of pain management that will require extensive efforts throughout biomedical science. The purpose of the present review is to highlight the critical role of the to devise improved translational models of pain for drug development. Despite high heterogeneity of painful conditions that involve cortical-dependent pain processing, current models often feature an overreliance on simple reflex-based measures and an emphasis on the absence, rather than presence, of behavior as evidence of analgesic efficacy. Novel approaches should focus on the restoration of operant and other CNS-mediated behavior under painful conditions.
Gene variants may contribute to individual differences in the experience of pain and the efficacy and reward of treatments. We explored gene variation in opioid-naïve and opioid-consuming patients undergoing elective lower extremity total joint replacement. We focused on 3 gene pathways including prostaglandin, gamma-aminobutyric acid (GABA)-ergic reward, and hepatic metabolism pathways. We report that for genes with possible or probable deleterious impact in these 3 pathways, opioid consumers had more gene variants than opioid-naïve patients (median 3 vs 1, P = .0092). We conclude that chronic opiate users may have genetic susceptibility to altered responses in reward/dependency and pain/inflammation pathways.
Pain ratings are almost ubiquitous in pain assessment, but their variability is high. Low correlations of continuous/numerical rating scales with categorical scales suggest that individuals associate different sensations with the same number on a scale, jeopardizing the interpretation of statistical results. We analyzed individual conceptions of rating scales and whether these conceptions can be utilized in the analysis of ratings of experimental stimuli in pain-free healthy individuals and people with reoccurring/persistent pain.
Preventing and treating opioid dependence and withdrawal is a major clinical challenge, and the underlying mechanisms of opioid dependence and withdrawal remain elusive. We hypothesized that prolonged morphine exposure or chronic inflammation-induced μ-opioid receptor activity serves as a severe stress that elicit neuronal alterations and recapitulates events during development. Here, we report that Wnt signaling, which is important in developmental processes of the nervous system, plays a critical role in withdrawal symptoms from opioid receptor activation in mice. Repeated exposures of morphine or peripheral inflammation produced by intraplantar injection of Complete Freund's Adjuvant significantly increases the expression of Wnt5b in the primary sensory neurons in dorsal root ganglion (DRG). Accumulated Wnt5b in DRG neurons quickly transmits to the spinal cord dorsal horn (DH) following naloxone treatment. In the DH, Wnt5b, acts through the atypical Wnt-Ryk receptor and alternative Wnt-YAP/TAZ signaling pathways, contributing to the naloxone-precipitated opioid withdrawal-like behavioral symptoms and hyperalgesia. Inhibition of Wnt synthesis and blockage of Wnt signaling pathways greatly suppress the behavioral and neurochemical alterations after naloxone-precipitated withdrawal. These findings reveal a critical mechanism underlying naloxone-precipitated opioid withdrawal, suggesting that targeting Wnt5b synthesis in DRG neurons and Wnt signaling in DH may be an effective approach for prevention and treatment of opioid withdrawal syndromes, as well as the transition from acute to chronic pain.