1 The Department of Palliative Medicine, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Yunnan Palliative Medicine Research Center, Yunnan 650118, China.
2 The Second Department of Medicine, the Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Yunnan 650118, China.
Exp Biol Med (Maywood). 2018 Jan;243(1):57-65. doi: 10.1177/1535370217740859. Epub 2017 Nov 2.
Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous HS may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of HS in BCP. We first measured the changes of serum HS in patients with BCP and analyzed the relationship between them, then investigated the effect of HS preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum HS level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with HS significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of HS preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with HS significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of HS preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous HS and exogenous HS in the development of BCP and present us a new strategy of pain management.
骨癌疼痛（BCP）是一种严重的痛觉过敏，发生于原发性骨肿瘤或转移至骨骼的晚期癌症。BCP 可严重降低生活质量，对现代医学构成挑战。研究表明，外源性 HS 可能作为神经保护剂，对中枢神经系统的某些疾病起作用。本研究旨在探讨 HS 在 BCP 中的镇痛作用。我们首先测量了 BCP 患者血清 HS 的变化，并分析了它们之间的关系，然后研究了 HS 预处理对 BCP 的影响，并在大鼠模型中探讨了其机制。我们的结果表明，血清 HS 水平与疼痛评分呈负相关。在大鼠 BCP 模型中，HS 预处理显著减轻了 BCP，表现为热痛觉过敏和机械性痛觉过敏的减少。HS 预处理的机制可能涉及脊髓中小胶质细胞的失活和炎症抑制，其中激活了增殖物激活受体γ/p38/Jun N-末端激酶通路。
影响陈述 骨癌疼痛（BCP）显著降低了患者的生活质量或预期寿命，并给社会带来了严重的健康负担。然而，由于 BCP 的确切机制仍不清楚，因此尚未开发出有效的治疗方法。目前有一些止痛药，但它们有一些不可避免的副作用。急需额外的治疗策略。首先，我们发现 HS 预处理显著减轻了 BCP，表现为热痛觉过敏和机械性痛觉过敏的减少。其次，阐明了 HS 预处理的机制。它可能涉及脊髓中小胶质细胞的失活和炎症抑制，其中激活了增殖物激活受体γ/p38/Jun N-末端激酶通路。这一新发现可能有助于我们理解内源性 HS 和外源性 HS 在 BCP 发展中的作用差异，并为我们提供一种新的疼痛管理策略。
