Characterization and comparison of rat monosodium iodoacetate and medial meniscal tear models of osteoarthritic pain

Abstract

Osteoarthritis (OA) is a degenerative form of arthritis that can result in loss of joint function and chronic pain. The pathological pain state that develops with OA disease involves plastic changes in the peripheral and central nervous systems, however, the cellular mechanisms underlying OA are not fully understood. We characterized the medial meniscal tear (MMT) surgical model and the intra-articular injection of monosodium iodoacetate (MIA) chemical model of OA in rats. Both models produced histological changes in the knee joint and associated bones consistent with OA pathology. Both models also increased p38 activation in the L3, but not L4 dorsal root ganglia (DRG), increased tyrosine hydroxylase immunostaining in the L3 DRG indicating sympathetic sprouting, and increased phosphorylated (p)CREB in thalamic neurons. In MIA-OA, but not MMT-OA rats, p38 and pERK were increased in the spinal cord, and pCREB was enhanced in the prefrontal cortex. Using in vivo electrophysiology, elevated spontaneous activity and increased responsiveness of wide dynamic range neurons to stimulation of the knee was found in both models. However, a more widespread sensitization was observed in the MIA-OA rats as neurons with paw receptive fields spontaneously fired at a greater rate in MIA-OA than MMT-OA rats. Taken together, the MIA and MMT models of OA share several common features associated with histopathology and sensitization of primary somatosensory pathways, but, observed differences between the models highlights unique consequences of the related specific injuries, and these differences should be considered when choosing an OA model and when interpreting data outcomes. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

“…Havelin et al showed that advanced OA pain is associated with central sensitization, and two aspects of central sensitization, spinal sensitization and descending facilitation, are observed in rats with persistent ongoing pain. Brederson et al stated that p38 and phosphorylated extracellular signal‐regulated kinase (pERK) were increased in the spinal cord, and that phosphorylated cAMP response element binding protein (pCREB) was enhanced in the prefrontal cortex in the MIA‐induced knee OA model. MIA‐induced knee OA is characterized by central sensitization and neuropathic pain.…”

“…With regard to the pain mechanism for hip OA, we have reported an animal model of monosodium iodoacetate (MIA)‐induced hip OA and evaluated the expression of calcitonin gene‐related peptide (CGRP) and activating transcription factor 3 (ATF3) in the dorsal‐root ganglia (DRG) and the expression of the ionized‐calcium‐binding adapter molecule 1 (Iba1) in the spinal cord . In MIA‐induced knee OA model in rats, some studies reported duloxetine attenuated the neuropathic pain . To the best of our knowledge, no report investigated the effect of duloxetine on neuropathic pain and its mechanism in hip OA animal model to date.…”

Pros and cons of mouse models for studying osteoarthritis

“…Therefore, this model is not commonly used to study the progression of OA as the damage it causes does not mimic true OA as well as certain other models. Instead, it is mainly used to observe and evaluate pain behavior and to assess the efficacy of therapeutic interventions to reduce inflammation and pain [36][37][38][39].…”

“…However, they do have utility for studying the mechanism by which OA causes pain and the behavioral changes resulting from this pain. Also, these models are useful for evaluating the efficacy of different drug therapies which can be used to alleviate the pain experienced by people afflicted with OA [32][33][34][35][36][37][38][39].…”

“…Naturally occurring X X X X [9][10][11] Genetically modified X X X X [12][13][14][15][16][17][18][19][20][21][22][23][24] Surgically induced (all) X X X X X [25][26][27][28][29][30] Chemically induced (all) X [31][32][33][34][35][36][37][38][39] Non-invasive induction X X X X X [40][41][42][43][44][45][46][47][48][49][50][51][52] [5,8,63,64]…”