In osteoarthritis (OA), pain is the dominant clinical symptom, yet the therapeutic approaches remain inadequate. The knowledge of the nociceptive mechanisms in OA, which will allow to develop effective therapies for OA pain, is of utmost need. In this study, we investigated the nociceptive mechanisms involved in post-traumatic OA pain, using the destabilization of the medial meniscus (DMM) mouse model. Our results revealed the development of peripheral pain sensitization, reflected by augmented mechanical allodynia. Along with the development of pain behaviour, we observed an increase in the expression of calcitonin gene-related peptide (CGRP) in both the sensory nerve fibers of the periosteum and the dorsal root ganglia. Interestingly, we also observed that other nociceptive mechanisms commonly described in non-traumatic OA phenotypes, such as infiltration of the synovium by immune cells, neuropathic mechanisms and also central sensitization were not present. Overall, our results suggest that CGRP in the sensory nervous system is underlying the peripheral sensitization observed after traumatic knee injury in the DMM model, highlighting the CGRP as a putative therapeutic target to treat pain in post-traumatic OA. Moreover, our findings suggest that the nociceptive mechanisms involved in driving pain in post-traumatic OA are considerably different from those in non-traumatic OA.

在骨关节炎 (OA) 中，疼痛是主要的临床症状，但治疗方法仍然不足。最需要了解 OA 的伤害感受机制，这将有助于开发有效的 OA 疼痛疗法。在这项研究中，我们使用内侧半月板 (DMM) 小鼠模型的不稳定来研究创伤后 OA 疼痛中涉及的伤害感受机制。我们的结果揭示了外周痛敏化的发展，这反映在增强的机械性异常性疼痛中。随着疼痛行为的发展，我们观察到降钙素基因相关肽（CGRP）在骨膜和背根神经节的感觉神经纤维中的表达增加。有趣的是，我们还观察到在非创伤性 OA 表型中常见的其他伤害感受机制，如免疫细胞对滑膜的浸润、神经病理性机制和中枢致敏作用均不存在。总体而言，我们的结果表明，感觉神经系统中的 CGRP 是 DMM 模型中膝外伤后观察到的外周敏化的基础，突出了 CGRP 作为治疗创伤后 OA 疼痛的推定治疗靶点。此外，我们的研究结果表明，在创伤后 OA 中引起疼痛的伤害感受机制与非创伤性 OA 有很大不同。强调 CGRP 作为治疗创伤后 OA 疼痛的推定治疗靶点。此外，我们的研究结果表明，在创伤后 OA 中引起疼痛的伤害感受机制与非创伤性 OA 有很大不同。强调 CGRP 作为治疗创伤后 OA 疼痛的推定治疗靶点。此外，我们的研究结果表明，在创伤后 OA 中引起疼痛的伤害感受机制与非创伤性 OA 有很大不同。