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Signaling mediated by soluble epoxide hydrolase (sEH) has been reported to play an important role in pain processing. Previous studies revealed that sEH activity is inhibited by specific binding of electrophiles to a redox-sensitive thiol (Cys521) adjacent to the catalytic center of the hydrolase. Here, we investigated if this redox-dependent modification of sEH is involved in pain processing using "redox-dead" knockin-mice (sEH-KI), in which the redox-sensitive cysteine is replaced by serine. However, behavioral characterization of sEH-KI mice in various animal models revealed that acute nociceptive, inflammatory, neuropathic, and visceral pain processing is not altered in sEH-KI mice. Thus, our results suggest that redox-dependent modifications of sEH are not critically involved in endogenous pain signaling in mice.
Many patients use opioids chronically before surgery; it is unclear if surgery alters the likelihood of ongoing opioid consumption in these patients.
Embedded behavioral medicine services are a common component of multidisciplinary chronic pain treatment programs. However, few studies have studied whether these services are associated with improved treatment outcomes.
To study the impact of anesthesia opioid-related outcomes and acute and chronic postsurgical pain, we organized a multicenter study that comprehensively combined detailed perioperative data elements from multiple institutions. By combining pre- and postoperative patient-reported outcomes with automatically extracted high-resolution intraoperative data obtained through the Multicenter Perioperative Outcomes Group (MPOG), the authors sought to describe the impact of patient characteristics, preoperative psychological factors, surgical procedure, anesthetic course, postoperative pain management, and postdischarge pain management on postdischarge pain profiles and opioid consumption patterns. This study is unique in that it utilized multicenter prospective data collection using a digital case report form integrated with the MPOG framework and database. Therefore, the study serves as a model for future studies using this innovative method. Full results will be reported in future articles; the purpose of this article is to describe the methods of this study.
Osteoarthritis (OA) is known to be a slowly progressive disease that alters all tissue compartments of the joint involved with a characteristic degradation of the cartilage, bone remodeling, and inflammation. One of the prominent symptoms in OA patients is pain, but a few radiological, inflammatory or structurally related biomarkers have shown little if any associations to pain. This study aimed to assess serum levels of 92 markers involved in inflammatory pathways in patients with knee OA (KOA) and evaluate their possible associations with the clinical pain intensity.
Whilst sensory and sympathetic neurons are known to innervate bone, previous studies have found it difficult to unequivocally identify and characterise only those that are of sensory origin. In this study, we have utilized an in vivo anterograde tracing technique to selectively label spinal afferent (sensory) nerve endings that innervate the periosteum and marrow cavity of murine long bones. Unilateral injections of dextran-biotin (anterograde tracer; 20% in saline, 50-100 nL) were made into L3-L5 dorsal root ganglia (DRG). After a 10-day recovery period to allow sufficient time for selective anterograde transport of the tracer to nerve terminal endings in bone, the periosteum (whole-mount) and underlying bone were collected, processed to reveal anterograde labelling, and immuno-labelled with antibodies directed against protein gene product (pan-neuronal marker; PGP9.5), tyrosine hydroxylase (sympathetic neuron marker; TH), calcitonin gene-related protein (peptidergic nociceptor marker; CGRP) and/or neurofilament 200 (myelinated axon marker; NF200). Anterograde labelled nerve endings were dispersed throughout the periosteum and marrow cavity, and could be identified in close apposition to blood vessels and at sites distant from them. The periosteum and the marrow cavity were each innervated by myelinated (NF200+) sensory neurons, and unmyelinated (NF200-) sensory neurons that were either peptidergic (CGRP+) or non-peptidergic (CGRP-). Spinal afferent nerve endings did not express TH, and lacked the cylindrical morphology around blood vessels characteristic of sympathetic innervation. This approach to selective labelling of sensory nerve terminal endings will help to better identify how different sub-populations of sensory neurons, and their peripheral nerve terminal endings, interact with bone. This article is protected by copyright. All rights reserved.
Early life administration of vincristine (VNC), commonly used to treat pediatric leukemia, evokes peripheral neuropathy and mechanical pain hypersensitivity in rats that lasts into adolescence. However, the degree to which VNC-evoked neuropathic pain persists throughout adulthood has yet to be examined. It also remains unclear if pediatric VNC exposure can 'prime' developing nociceptive pathways and thereby exacerbate chronic pain following subsequent trauma later in life. To address these issues, rats received five total doses of VNC (60 µg/kg; or vehicle) on postnatal days (P) 11, 13, 17, 19 and 21 followed by a hindpaw surgical incision during adulthood. In addition, in order to model the clinical scenario where cancer relapse necessitates another round of chemotherapy, separate groups of rats that had been treated with VNC (or vehicle) as neonates were subsequently administered VNC as adults (five injections at 100 µg/kg). Intraepidermal nerve fiber density and baseline mechanical pain sensitivity were similar between the neonatal VNC and vehicle-treated littermate controls at 13-15 weeks of age, suggesting that the peripheral neuropathy, and resulting chronic pain, had resolved by adulthood. Importantly, there was no significant overall effect of early life VNC on the severity of post-operative pain following adult incision. Similarly, prior VNC exposure did not significantly influence the degree of mechanical pain hypersensitivity produced by adult VNC treatment. Collectively, these findings suggest that early life VNC administration does not increase the susceptibility to develop chronic pain as adults.
This article reviews current headache disability measures and clinical need, as well as presenting the rationale for a new measure addressing work-related disability in migraine patients and the steps devoted to this aim.