Browse by Audience
Knee pain in osteoarthritis is complex and complicated by the fact that osteoarthritis is considered to be a disorder of multiple phenotypes. This complexity challenges our understanding as to why some people remain relatively symptom-free, while others progress to persistent pain. One approach to understanding the mechanisms underlying the transition to persistent pain is by identifying pain susceptibility phenotypes in people with or at risk of knee osteoarthritis. Using variables representative of the multidimensional nature of pain in people who were free of persistent pain, we identified four phenotypes characterised by low pressure pain thresholds and temporal summation and not psychosocial factors in those who developed persistent pain two years later. The group with the highest proportion of low pressure pain thresholds and a moderate proportion with facilitated temporal summation had twice the odds of developing persistent knee pain. This work provides preliminary insights into the critical importance of altered neurobiological mechanisms of pain signalling that contributes to development of chronic, persistent pain in knee osteoarthritis.
Learn More >Neural function depends on maintaining cellular membrane potentials as the basis for electrical signaling. Yet in mammals and insects, neuronal and glial membrane potentials can reversibly depolarize to zero, shutting down neural function by the process of spreading depolarization (SD) that collapses the ion gradients across membranes. SD is not evident in all metazoan taxa with centralized nervous systems. We consider the occurrence and similarities of SD in different animals and suggest that it is an emergent property of nervous systems that have evolved to control complex behaviours requiring energetically expensive, rapid information processing in a tightly regulated extracellular environment. Whether SD is beneficial or not in mammals remains an open question. However, in insects it is associated with the response to harsh environments and may provide an energetic advantage that improves the chances of survival. The remarkable similarity of SD in diverse taxa supports a model systems approach to understanding the mechanistic underpinning of human neuropathology associated with migraine, stroke and traumatic brain injury.
Learn More >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.
Learn More >Many patients use opioids chronically before surgery; it is unclear if surgery alters the likelihood of ongoing opioid consumption in these patients.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >