Osteoarthritis (OA) is a potentially disabling disease whose progression is dependent on several risk factors. OA management usually involves the use of non-steroidal anti-inflammatory drugs (NSAIDs) that are the primary pharmacological treatments of choice. However, NSAIDs have often been associated with unwanted side effects. Cyclooxygenase (COX)-2 specific inhibitors, such as celecoxib, have been successfully used as an alternative in the past for OA treatment and have demonstrated fewer side effects. While abundant data are available for the clinical efficacy of drugs used for OA treatment, little is known about the disease-modifying effects of these agents. A previous review published by Zweers et al. (2010) assessed the available literature between 1990 and 2010 on the disease-modifying effects of celecoxib. In the present review, we aimed to update the existing evidence and identify evolving concepts relating to the disease-modifying effects of not just celecoxib, but also other NSAIDs. We conducted a review of the literature published from 2010 to 2016 dealing with the effects, especially disease-modifying effects, of NSAIDs on cartilage, synovium, and bone in OA patients. Our results show that celecoxib was the most commonly used drug in papers that presented data on disease-modifying effects of NSAIDs. Further, these effects appeared to be mediated through the regulation of prostaglandins, cytokines, and direct changes to tissues. Additional studies should be carried out to assess the disease-modifying properties of NSAIDs in greater detail.

Vibration acceleration through whole body vibration has been reported to promote fracture healing. However, the mechanism responsible for this effect remains unclear. Purpose of this study was to determine whether vibration acceleration directly affects cells around the fracture site and promotes endochondral ossification. Four-week-old female Wistar Hannover rats were divided into two groups (vibration [V group] and control [C group]). The eighth ribs on both sides were cut vertically using scissors. From postoperative day 3 to 11, vibration acceleration using Power Plate ® (30 Hz, low amplitude [30-Low], 10 min/day) was applied in the V group. Mature calluses appeared earlier in the V group than in the C group by histological analysis. The GAG content in the fracture callus on day 6 was significantly higher in the V group than in the C group. The mRNA expressions of SOX-9, aggrecan, and Col-II in the fracture callus on day 6 and Col-X on day 9 were significantly higher in the V group than in the C group. For in vitro analysis, four different conditions of vibration acceleration (30 or 50 Hz with low or high amplitude [30-Low, 30-High, 50-Low, and 50-High], 10 min/day) were applied to a prechondrogenic cell (ATDC5) and an undifferentiated cell (C3H10T1/2). There was no significant difference in cell proliferation between the control and any of the four vibration conditions for both cell lines. For both cell lines, alcian blue staining was greater under 30-Low and 50-Low conditions than under control as well as 30-High and 50-High conditions on days 7 and 14. Vibration acceleration under 30-L condition upregulated chondrogenic gene expressions of SOX-9, aggrecan, Col-II, and Col-X. Lowamplitude vibration acceleration can promote endochondral ossification in the fracture healing in vivo and chondrogenic differentiation in vitro.

Purpose: Thermal radiofrequency ablation (RF) is a minimally invasive procedure used to denervate the pain-transmitting peripheral nerves in chronic pain patients. Standard RF (SRF) and cooled RF (CRF) are two commonly used thermal ablation technologies hypothesized to provide pain relief by temporarily blocking signaling of the pain-transmitting sensory nerves and eliminating perception of pain in the central nervous system (CNS). CRF overcomes the lesion size limitations inherent to SRF administered at 80 C by circulating fluid around a 60 C probe tip to remove heat from tissue adjacent to the electrode, thereby delivering energy within a larger radius. Although previous ex vivo studies have evaluated RF lesion size, the underlying central and/or peripheral mechanisms for RF-induced pain relief have not been characterized. Here, we present the first in vivo analysis of pathophysiological changes that occur in response to either SRF or CRF. We hypothesize that enhanced delivery of thermal energy provided by CRF correlates with sustained peripheral and/or CNS neuroadaptations. To test this hypothesis, we evaluated functional, structural, and biochemical responses in rodents exposed to sciatic nerve (SN) RF. Methods: As previously reported, sciatic nerve RF ablations can be performed in rats to mimic clinical applications allowing for rapid assessment of changes that occur over extended durations in humans. (Note: Two weeks of a rat lifespan corresponds to one human year.) In one group, male Lewis rats were exposed to recommended human clinical parameters of SRF (90s, 22-gauge, 5mm active tip, 80 C) or CRF (150s, 17-gauge, 2mm active tip, 60 ) on the SN and assessed for immediate changes. Another group of Lewis rats were exposed to optimized levels of SRF (50s) or CRF (80s) to allow for long-term evaluation with minimal collateral damage to surrounding tissues and severe adverse events. Power output was recorded to calculate total energy delivered from the generator. Following ablation, rats were assessed for nerve function (electromyography, EMG) and lesion volume (9.4T Bruker MR scanner). EMG measurements were also taken repeatedly over the course of 12 weeks. At necropsy, nerves were harvested for histological analysis (H&E). A subsequent study exposed male Lewis rats to a pain phenotype in which local inflammation was induced via Freund's complete adjuvant (FCA) injection in the left hind paw prior to ablation. Rats in the pain study were evaluated weekly via von-Frey for changes in left hind paw mechanosensitivity. At day 35 post-ablation necropsy, brains were collected for immunohistochemical analysis of CNS protein expression in brain regions known to be impacted by chronic pain. Results: Utilizing human clinical parameters, CRF delivered~3.5 times greater energy than SRF in vivo and remained consistent when optimized for the smaller rodent anatomy. In histological images of CRF nerves, a region of lesser thermal damage (pink) was flanked by regions of more severe damage (purple), paralleling the thermal pr...