Pathological Characteristics of Monosodium Iodoacetate-Induced Osteoarthritis in Rats

BACKGROUND@#This study aimed to identify pain-related behavior and pathological characteristics of the knee joint in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA). @*METHODS@#Knee joint inflammation was induced by intra-articular injection of MIA (4 mg/50 lL, n = 14) in 6-weekold male rats. Knee joint diameter, weight-bearing percentage on the hind limb during walking, the knee bending score, and paw withdrawal to mechanical stimuli were measured to evaluate edema and pain-related behavior for 28 d after MIA injection. Histological changes in the knee joints were evaluated using safranin O fast green staining on days 1, 3, 5, 7, 14, and 28 after OA induction (n = 3, respectively). Changes in bone structure and bone mineral density (BMD) were examined 14 and 28 d after OA (n = 3, respectively) using micro-computed tomography (CT). @*RESULTS@#The knee joint diameter and knee bending scores of the ipsilateral joint significantly increased 1 d after MIA injection, and the increased knee joint diameter and knee bending score persisted for 28 d. Weight-bearing during walking and paw withdrawal threshold (PWT) decreased from 1 and 5 d, respectively, and were maintained up to 28 d after MIA. Cartilage destruction started on day 1, and Mankin scores for bone destruction significantly increased for 14 d, as shown by micro-CT imaging. @*CONCLUSION@#The present study demonstrated that histopathological structural changes in the knee joint due to inflammation started soon after MIA injection, which induced OA pain from inflammation-related acute pain to spontaneous and evoked associated chronic pain.

Low-Level Laser Irradiation Improves Motor Recovery After Contusive Spinal Cord Injury in Rats

This study investigated the therapeutic effects of low-level laser irradiation (LLLI) on the recovery of motor function and its underlying mechanisms in rats with spinal cord injury (SCI). The spinal cord was contused at the T11 level using a New York University impactor. Thirty-eight rats were randomly divided into four groups: LLLI with 0.08 J, 0.4 J, 0.8 J, and sham. We transcutaneously applied at the lesion site of the spinal contusive rats 5 min after injury and then daily for 21 days. The Basso, Beattie and Bresnahan (BBB) locomotor scale and combined behavioral score (CBS) were used to evaluate motor function. The spinal segments of rostral and caudal from the lesion site, the epicenter, and L4–5 were collected from normal and the all groups at 7 days after SCI. The expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) was compared across groups in all regions. In the present study, LLLI with 0.4 J and 0.8 J led to a significant improvement in motor function compared to sham LLLI, which significantly decreased TNF-α expression at the lesion epicenter and reduced iNOS expression in the caudal segment for all LLLI groups and in the L4–5 segments for the 0.4 J and 0.8 J groups when compared to sham LLLI group. Our results demonstrate that transcutaneous LLLI modulate inflammatory mediators to enhance motor function recovery after SCI. Thus, LLLI in acute phase after SCI might have therapeutic potential for neuroprotection and restoration of motor function following SCI.

The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 microl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

Effect of the Combination of CI-988 and Morphine on Neuropathic Pain after Spinal Cord Injury in Rats

Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain.

Loss of hsp70.1 Decreases Functional Motor Recovery after Spinal Cord Injury in Mice

Heat shock proteins (HSPs) are specifically induced by various forms of stress. Hsp70.1, a member of the hsp70 family is known to play an important role in cytoprotection from stressful insults. However, the functional role of Hsp70 in motor function after spinal cord injury (SCI) is still unclear. To study the role of hsp70.1 in motor recovery following SCI, we assessed locomotor function in hsp70.1 knockout (KO) mice and their wild-type (WT) mice via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, before and after spinal hemisection at T13 level. We also examined lesion size in the spinal cord using Luxol fast blue/cresyl violet staining. One day after injury, KO and WT mice showed no significant difference in the motor function due to complete paralysis following spinal hemisection. However, when it compared to WT mice, KO mice had significantly delayed and decreased functional outcomes from 4 days up to 21 days after SCI. KO mice also showed significantly greater lesion size in the spinal cord than WT mice showed at 21 days after spinal hemisection. These results suggest that Hsp70 has a protective effect against traumatic SCI and the manipulation of the hsp70.1 gene may help improve the recovery of motor function, thereby enhancing neuroprotection after SCI.

Long-term Follow-up of Cutaneous Hypersensitivity in Rats with a Spinal Cord Contusion

Sometimes, spinal cord injury (SCI) results in various chronic neuropathic pain syndromes that occur diffusely below the level of the injury. It has been reported that behavioral signs of neuropathic pain are expressed in the animal models of contusive SCI. However, the observation period is relatively short considering the natural course of pain in human SCI patients. Therefore, this study was undertaken to examine the time course of mechanical and cold allodynia in the hindpaw after a spinal cord contusion in rats for a long period of time (30 weeks). The hindpaw withdrawal threshold to mechanical stimulation was applied to the plantar surface of the hindpaw, and the withdrawal frequency to the application of acetone was measured before and after a spinal contusion. The spinal cord contusion was produced by dropping a 10 g weight from a 6.25 and 12.5 mm height using a NYU impactor. After the injury, rats showed a decreased withdrawal threshold to von Frey stimulation, indicating the development of mechanical allodynia which persisted for 30 weeks. The withdrawal threshold between the two experimental groups was similar. The response frequencies to acetone increased after the SCI, but they were developed slowly. Cold allodynia persisted for 30 weeks in 12.5 mm group. The sham animals did not show any significant behavioral changes. These results provide behavioral evidence to indicate that the below-level pain was well developed and maintained in the contusion model for a long time, suggesting a model suitable for pain research, especially in the late stage of SCI or for long term effects of analgesic intervention.