Pain-related behavior and the characteristics of dorsal-root ganglia in a rat model of hip osteoarthritis induced by mono-iodoacetate

Abstract

The principal aim of this study was to clarify the time course of pain-related behavior and pain-related sensory innervation in a rat model of hip osteoarthritis (OA) induced by intra-articular injection of mono-iodoacetate (MIA). Using 6-week-old male Sprague Dawley rats, 25 μl of sterile saline of 1% Fluoro-Gold solution (FG) (control group; n = 30) and 25 μl of sterile saline of 1% FG with 2 mg of MIA (MIA group; n = 30) was injected into the right hip joints. Gait function was evaluated using a CatWalk system after 7, 14, 28, 42, and 56 days (n = 5, respectively). Neurons in the dorsal root ganglion (DRG) between L1 and L5 were immunostained for calcitonin gene-related peptide (CGRP) and activating transcription factor-3 (ATF3). Gait analysis revealed the mean six parameters of hind paws at all time points were significantly lower in the MIA group (p = 0.05). The number of CGRP-immunoreactive (-IR) DRG neurons was significantly increased on days 7, 14, 28, and 42 peaking at 14 days in the MIA group. By contrast, expression of ATF3-IR in FG-labeled DRG neurons was significantly increased on days 42 and 57. The FG-labeled DRG neurons were distributed between L1 and L5, mainly at the L4 level. Pain-related behavior indicated by gait disturbance was observed in a MIA model of hip OA in rat. Early elevation of CGRP expression and late expression of ATF-3 were demonstrated in DRG neurons, possibly reflecting inflammatory pain and neuropathic pain in hip OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1424–1430, 2017.