Abstract
SummaryObjectivePain is the main reason patients report Osteoarthritis (OA), yet current analgesics remain relatively ineffective. This study investigated both peripheral and central mechanisms that lead to the development of OA associated chronic pain.DesignThe monoiodoacetate (MIA) model of OA was investigated at early (2–6 days post injection) and late (>14 days post injection) time points. Pain-like behaviour and knee histology were assessed to understand the extent of pain due to cartilage degradation. Electrophysiological single-unit recordings were taken from spinal wide dynamic range (WDR) neurons to investigate Diffuse Noxious Inhibitory Controls (DNIC) as a marker of potential changes in descending controls. Immunohistochemistry was performed on dorsal root ganglion (DRG) neurons to assess any MIA induced neuronal damage. Furthermore, qPCR was used to measure levels of glia cells and cytokines in the dorsal horn.ResultsBoth MIA groups develop pain-like behaviour but only late phase (LP) animals display extensive cartilage degradation. Early phase animals have a normally functioning DNIC system but there is a loss of DNIC in LP animals. We found no evidence for neuronal damage caused by MIA in either group, yet an increase in IL-1β mRNA in the dorsal horn of LP animals.ConclusionThe loss of DNIC in LP MIA animals suggests an imbalance in inhibitory and facilitatory descending controls, and a rise in the mRNA expression of IL-1β mRNA suggest the development of central sensitisation. Therefore, the pain associated with OA in LP animals may not be attributed to purely peripheral mechanisms.
Highlights
Pain is the major symptom of OA and the reason patients report the disease,[1] yet the discordance between radiographic joint damage observed and the associated pain renders it difficult to understand which aspects of the disease trigger pain.[2]
Diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous inhibitory control of spinal wide dynamic range (WDR) neurons, where both noxious and innocuous evoked neuronal activity can be strongly inhibited by a second concomitant noxious conditioning stimulus outside of the receptive field.11e13 The activation of supraspinal structures and functional descending controls are required for DNIC to induce neuronal inhibition, as
Variations with monoaminergic descending pathways have been demonstrated over the course of the MIA model, so this study investigated DNIC in both the early inflammatory phase (EP) and late chronic phases (LP) of the model.[24]
Summary
Pain is the major symptom of OA and the reason patients report the disease,[1] yet the discordance between radiographic joint damage observed and the associated pain renders it difficult to understand which aspects of the disease trigger pain.[2]. Diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous inhibitory control of spinal wide dynamic range (WDR) neurons, where both noxious and innocuous evoked neuronal activity can be strongly inhibited by a second concomitant noxious conditioning stimulus outside of the receptive field.11e13 The activation of supraspinal structures and functional descending controls are required for DNIC to induce neuronal inhibition, as. No damage Some loss of toluidine blue staining Small superficial lesions of the articular cartilage Small lesions immediately below the superficial layer of articular cartilage Large lesions or erosion of the articular cartilage covering up to 20% of the condyle Loss of articular cartilage tissue from 20% to 50% of the condyle surface Loss of articular cartilage tissue from 50% to 80% of the condyle surface Loss of articular cartilage tissue from more than 80% of the condyle surface are contributing to the maintenance of chronic pain.13,17e19 the human counterpart of DNIC, Conditioned Pain Modulation (CPM), has been demonstrated to be lost in a variety of chronic pain states.[20,21] measuring CPM responses in patients has been shown to predict the likelihood of patients developing chronic pain and how responsive they will be to drugs that restore this descending inhibition.[22,23] Overall, assessing DNIC or CPM provides a useful method for investigating the functionality of descending controls
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
