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Increased vascular endothelial growth factor (VEGF) levels are associated with OA progression. Indeed, VEGF appears to be involved in OA specific pathologies including cartilage degeneration, osteophyte formation, subchondral bone cysts and sclerosis, synovitis, and pain. Moreover, a wide range of studies suggests that inhibition of VEGF signaling reduces OA progression. This review highlights both the potential significance of VEGF in OA pathology and pain as well as potential benefits of inhibition of VEGF and its receptors as an OA treatment. With the emergence of the clinical use of anti-VEGF therapy outside of OA, both as high dose systemic treatments and low dose local treatments, these particular therapies are now more widely understood. Currently, there is no established disease-modifying drug available for patients with OA, which warrants continued study of the inhibition of VEGF in OA, as standalone or adjuvant therapy.

Objective. To verify the biologic links between progressive cellular and structural alterations within knee joint components and development of symptomatic chronic pain that are characteristic of osteoarthritis (OA), and to investigate the molecular basis of alterations in nociceptive pathways caused by OA-induced pain.Methods. An animal model of knee joint OA pain was generated by intraarticular injection of monoiodoacetate (MIA) in Sprague-Dawley rats, and symptomatic pain behavior tests were performed. Relationships between development of OA with accompanying pain responses and gradual alterations in cellular and structural knee joint components (i.e., cartilage, synovium, meniscus, subchondral bone) were examined by histologic and immunohistologic analysis, microscopic examination, and microfocal computed tomography. Progressive changes in the dynamic interrelationships between peripheral knee joint tissue and central components of nociceptive pathways caused by OA-induced pain were examined by investigating cytokine production and expression in sensory neurons of the dorsal root ganglion and spinal cord.Results. We observed that structural changes in components of the peripheral knee joint correlate with alterations in the central compartments (dorsal root ganglia and the spinal cord) and symptomatic pain assessed by behavioral hyperalgesia. Our comparative gene expression studies revealed that the pain pathways in MIA-induced knee OA may overlap, at least in part, with neuropathic pain mechanisms. Similar results were also observed upon destabilization of the knee joint in the anterior cruciate ligament transection and destabilization of the medial meniscus models of OA.Conclusion. Our results indicate that MIAinduced joint degeneration in rats generates an animal model that is suitable for mechanistic and pharmacologic studies on nociceptive pain pathways caused by OA, and provide key in vivo evidence that OA pain is caused by central sensitization through communication between peripheral OA nociceptors and the central sensory system. Furthermore, our data suggest a mechanistic overlap between OA-induced pain and neuropathic pain.

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Background: Digital patient engagement platforms are designed to improve the efficacy of the perioperative surgical home, but the currently available solutions have shown low patient and provider adoption. The purpose of this study was to evaluate the effectiveness of a text-messaging (Short Message Service [SMS]) bot with respect to patient engagement following joint replacement procedures in a randomized clinical trial. Methods: One hundred and fifty-nine patients (83 patients in the control group and 76 patients in the intervention group) were enrolled in a randomized controlled trial comparing the effectiveness of an SMS bot (intervention group) with the traditional perioperative education process (control group) in patients undergoing primary total knee or hip arthroplasty. There were no significant differences in the demographic characteristics between the 2 groups. The primary outcome of time participating in home-based exercises and the secondary outcomes of knee range of motion, the use of narcotics, visual analog scale (VAS) mood score, telephone calls to the office, patient satisfaction, and visits to the emergency department were measured and were compared between the 2 groups. Continuous outcomes were analyzed using linear regression, and categorical outcomes were analyzed using the Pearson chi-square test. Results: Patients in the intervention group exercised for 8.6 minutes more per day: a mean time (and standard deviation) of 46.4 ± 17.4 minutes compared with 37.7 ± 16.3 minutes for the control group (p < 0.001). The intervention group had an improved mood (mean VAS, 7.5 ± 1.8 points compared with 6.5 ± 1.7 points for the control group; p < 0.001), stopped their narcotic medications 10 days sooner (mean time, 22.5 ± 13.4 days compared with 32.4 ± 11.8 days for the control group; p < 0.001), placed fewer telephone calls to the surgeon’s office (mean calls, 0.6 ± 0.8 compared with 2.6 ± 3.4 for the control group; p < 0.001), and had greater knee range of motion 3 weeks after the surgical procedure (mean flexion, 101.2° ± 11.2° compared with 93.8° ± 14.5° for the control group; p = 0.008), but had an equal range of motion at 6 weeks. There was a trend toward fewer visits to the emergency department in the intervention group, but this comparison lacked statistical power. Conclusions: An SMS bot can improve clinical outcomes and increase patient engagement in the early postoperative period in patients undergoing hip or knee arthroplasty. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

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