Neuro-Skeletal Circuits Group, Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
Instituto de Engenharia Biomédica (INEB), Universidade do Porto, Porto, Portugal.
Sci Rep. 2020 Sep 17;10(1):15271. doi: 10.1038/s41598-020-72227-9.
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。了解 OA 中的伤害感受机制将有助于开发治疗 OA 疼痛的有效方法，这是当务之急。在这项研究中，我们使用内侧半月板不稳定（DMM）小鼠模型研究了创伤后 OA 疼痛涉及的伤害感受机制。我们的结果表明，外周疼痛敏化的发展，表现为机械性超敏反应增强。随着疼痛行为的发展，我们观察到骨膜和背根神经节中的感觉神经纤维中降钙素基因相关肽（CGRP）的表达增加。有趣的是，我们还观察到，其他在非创伤性 OA 表型中通常描述的伤害感受机制，如滑膜中免疫细胞浸润、神经病理性机制和中枢敏化，并不存在。总的来说，我们的结果表明，感觉神经系统中的 CGRP 是 DMM 模型中创伤性膝关节损伤后观察到的外周敏化的基础，这突出了 CGRP 作为治疗创伤后 OA 疼痛的潜在治疗靶点的可能性。此外，我们的发现表明，驱动创伤后 OA 疼痛的伤害感受机制与非创伤性 OA 中的伤害感受机制有很大的不同。
