Kinematic and dynamic gait compensations resulting from knee instability in a rat model of osteoarthritis

Abstract

IntroductionOsteoarthritis (OA) results in pain and disability; however, preclinical OA models often focus on joint-level changes. Gait analysis is one method used to evaluate both preclinical OA models and OA patients. The objective of this study is to describe spatiotemporal and ground reaction force changes in a rat medial meniscus transection (MMT) model of knee OA and to compare these gait measures with assays of weight bearing and tactile allodynia.MethodsSixteen rats were used in the study. The medial collateral ligament (MCL) was transected in twelve Lewis rats (male, 200 to 250 g); in six rats, the medial meniscus was transected, and the remaining six rats served as sham controls. The remaining four rats served as naïve controls. Gait, weight-bearing as measured by an incapacitance meter, and tactile allodynia were assessed on postoperative days 9 to 24. On day 28, knee joints were collected for histology. Cytokine concentrations in the serum were assessed with a 10-plex cytokine panel.ResultsWeight bearing was not affected by sham or MMT surgery; however, the MMT group had decreased mechanical paw-withdrawal thresholds in the operated limb relative to the contralateral limb (P = 0.017). The gait of the MMT group became increasingly asymmetric from postoperative days 9 to 24 (P = 0.020); moreover, MMT animals tended to spend more time on their contralateral limb than their operated limb while walking (P < 0.1). Ground reaction forces confirmed temporal shifts in symmetry and stance time, as the MMT group had lower vertical and propulsive ground reaction forces in their operated limb relative to the contralateral limb, naïve, and sham controls (P < 0.05). Levels of interleukin 6 in the MMT group tended to be higher than naïve controls (P = 0.072). Histology confirmed increased cartilage damage in the MMT group, consistent with OA initiation. Post hoc analysis revealed that gait symmetry, stance time imbalance, peak propulsive force, and serum interleukin 6 concentrations had significant correlations to the severity of cartilage lesion formation.ConclusionThese data indicate significant gait compensations were present in the MMT group relative to medial collateral ligament (MCL) injury (sham) alone and naïve controls. Moreover, these data suggest that gait compensations are likely driven by meniscal instability and/or cartilage damage, and not by MCL injury alone.

Activation of neuronal Kv7/KCNQ/M-channels by the opener QO58-lysine and its anti-nociceptive effects on inflammatory pain in rodents

“…When challenged by CFA under chronic conditions, rats can transfer their bodyweight from the irritated paw to the healthy counterpart [25,26] . Therefore, the weight difference between the paw pair reflects the severity of pain.…”

Animal Models of Osteoarthritis: Challenges of Model Selection and Analysis

“…The magnitude at which the animal withdraws its foot is reported as the paw withdrawal threshold, and a lower paw withdrawal threshold is taken to represent increased sensitivity and neuropathic pain in the distal limb. Decreased paw withdrawal thresholds have been reported in a number of rat OA models including MMT (42,43), partial medial meniscectomy (44), and monosodium iodoacetate injection (44). When the filament is applied, however, it has been reported that filaments with stiffness greater than 16 g may lift the rat's foot (44).…”

“…There is currently no standard method of gait analysis for use in animal OA models. Published methods have included scoring based on apparent lameness (40), measurement of stride length and limb rotation from inked paw prints in rats (48), measurement of dynamic force application using a pressure-sensitive walkway (42,46), and fluoroscopic measurements of hind limb motion (47). In larger animals, gait and functionality measures such as kinematic marker analysis, ground reaction force measurements, and observational gait assessment have been applied to study OA-related changes for conditions including dog hip OA (49), lameness in horses (50), and postsurgical sheep knee OA (51).…”

Animal Models of Meniscal Injury in Post-Traumatic Arthritis

“…Signifi cant differences in serum cytokines were not identifi ed between groups. Histological lesions were signifi cantly worse in MMT/MCLT than MCLT [ 70 ]. Thus, MMT/MCLT produces very distinctive functional and histological defi ciencies that MCLT alone does not.…”

“…The additional effect of MMT compared to MCLT alone has been recently investigated in Lewis rats followed for 28 days postoperatively [ 70 ]. MMT/MCLT limbs had increased mechanical allodynia compared to unoperated in the same animal, but compared to control animals, there was only a trend to increased mechanical allodynia in MMT/MCLT groups, and no difference between surgical groups.…”