Objective. Interleukin-17 (IL-17) is considered a proinflammatory cytokine, but whether neuronal IL-17 receptors contribute to the generation of arthritic pain is unknown. This study was undertaken to explore whether IL-17A acts on neurons, whether it sensitizes joint nociceptors, and whether neutralization of IL-17 is antinociceptive.Methods. We recorded action potentials from rat joint nociceptors after intraarticular injection of IL-17A. We studied the expression of the IL-17A receptor in the rat dorsal root ganglia (DRG), explored the effect of IL-17A on signaling pathways in cultured rat DRG neurons, and using patch clamp recordings, monitored changes of excitability by IL-17A. We tested whether an antibody to IL-17 influences pain behaviors in mice with antigen-induced arthritis (AIA).Results. A single injection of IL-17A into the rat knee joint elicited a slowly developing and long-lasting sensitization of nociceptive C fibers of the joint to mechanical stimuli, which was not attenuated by neutralizing tumor necrosis factor ␣ or IL-6. The IL-17A receptor was visualized in most rat DRG neurons, the cell bodies of primary sensory neurons. In isolated and cultured rat DRG neurons, IL-17A caused rapid phosphorylation of protein kinase B and ERK, and it rapidly enhanced excitability. In mice with unilateral AIA in the knee, an antibody against IL-17 improved the guarding score and reduced secondary mechanical hyperalgesia at the ipsilateral paw.Conclusion. Our findings indicate that IL-17A has the potential to act as a pain mediator by targeting IL-17 receptors in nociceptive neurons, and these receptors are particularly involved in inflammation-evoked mechanical hyperalgesia.

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One difficulty in revision total knee arthroplasty (TKA) is the management of distal femoral bone defects in which a joint line elevation (JLE) is likely to occur. Although JLE has been associated with inferior clinical results, the effect that an elevated joint line has on knee contact forces has not been investigated. To understand the clinical observations and elaborate the potential risk associated with a JLE, we performed a virtual TKA on the musculoskeletal models of four subjects. Tibio-and patellofemoral joint contact forces (JCF) were calculated for walking and stair climbing, varying the location of the joint line. An elevation of the joint line primarily affected the patellofemoral joint with JCF increases of as much as 60% of the patient's body weight (BW) at 10-mm JLE and 90% BW at 15-mm JLE, while the largest increase in tibiofemoral JCF was only 14% BW. This data demonstrates the importance of restoring the joint line, as it plays a critical role for the magnitudes of the JCFs, particularly for the patellofemoral joint. JLE caused by managing distal femoral defects with downsizing and proximalizing the femoral component could increase the patellofemoral contact forces, and may be a contributing factor to postoperative complications such as pain, polyethylene wear, and limited function. ß

Background:The tetraspanin CD63 is known to regulate protein trafficking, leukocyte recruitment, and adhesion processes. Results: Silencing of CD63 disrupts complex formation between ␤1 integrin and VEGFR2, resulting in impaired downstream signaling. Conclusion: CD63 supports VEGFR2 activation and signaling in vitro and in vivo. Significance: A novel role for the tetraspanin CD63 in the convergence between integrin and growth factor signaling in angiogenesis.

Objective. Significant joint pain is usually widespread beyond the affected joint, which results from the sensitization of nociceptive neurons in the central nervous system (central sensitization). This study was undertaken to explore whether the proinflammatory cytokine interleukin-6 (IL-6) in the joint induces central sensitization, whether joint inflammation causes the release of IL-6 from the spinal cord, and whether spinal IL-6 contributes to central sensitization.Methods. In anesthetized rats, electrophysiologic recordings of spinal cord neurons with sensory input from the knee joint were made. Neuronal responses to mechanical stimulation of the rat knee and leg were monitored. IL-6 and soluble IL-6 receptor (sIL-6R) were applied to the knee joint or the spinal cord. Spinal release of IL-6 was measured by enzyme-linked immunosorbent assay. Soluble gp130, which neutralizes IL-6/ sIL-6R, was spinally applied during the development of joint inflammation or during established inflammation. Conclusion. Our findings indicate that the generation of joint pain in the rat involves not only IL-6 in the joint but also IL-6 released from the spinal cord. Spinal IL-6 contributes to central sensitization and thus promotes the widespread hyperalgesia observed in the course of joint disease.

ObjectiveAfter reverse shoulder arthroplasty (RSA) external and internal rotation will often remain restricted. A postoperative alteration of the biomechanics in the remaining cuff is discussed as a contributing factor to these functional deficits.MethodsIn this study, muscle moment arms as well as origin-to-insertion distance (OID) were calculated using three-dimensional models of the shoulder derived from CT scans of seven cadaveric specimens.ResultsMoment arms for humeral rotation are significantly smaller for the cranial segments of SSC and all segments of TMIN in abduction angles of 30 degrees and above (p ≤ 0.05). Abduction moment arms were significantly decreased for all segments (p ≤ 0.002). OID was significantly smaller for all muscles at the 15 degree position (p ≤ 0.005), apart from the cranial SSC segment.ConclusionsReduced rotational moment arms in conjunction with the decrease of OID may be a possible explanation for the clinically observed impaired external and internal rotation.

Our findings could explain clinically improved rotation in lateralized RSA in comparison to nonlateralized RSA.

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