Based on the concept of "blood exhaustion" from The Inner Canon of Yellow Emperor （《黄帝内经》）， a three-stage syndrome differentiation and treatment strategy for cancer-related anorexia-cachexia syndrome is proposeed. In the cancer-induced anorexia stage， the pathogenesis is characterized by cancer consuming the spleen and stomach， leading to stagnation of transportation and transformation in the middle jiao （焦）. Treatment should focus on strengthening the spleen， promoting appetite， dispersing accumulation， and aiding digestion， with modified Zisheng Pills （资生丸） in Extensive Notes on Medicine from Xian Xing Studio （《先醒斋医学广笔记》） or Zisheng Decoction （资生汤） in Records of Chinese Medicine with Reference to Western Medicine （《医学衷中参西录》）. In the pre-cachectic stage of malnutrition， the pathogenesis involves insufficient nourishment of blood and qi with essence depletion hindering production. Treatment should focus on nourishing blood and harmonizing ying （营）， warming yang and supplementing qi， and modified Huangqi Jianzhong Decoction （黄芪建中汤） can be used. In the cachectic stage， the pathogenesis involves blood deficiency and essence exhaustion， with blood stasis obstructing the collaterals. The therapeutic approach should focus on tonifying deficiency and replenishing essence， unblocking collaterals， and removing stasis， and modified Buzhong Yiqi Decoction （补中益气汤） and Zuo Gui Beverage （左归饮） are suggested.

[Objective] : To systematically evaluate the overall efficacy of external application of traditional Chinese medicine (EA-TCM) in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain (CIBP). [Methods] : We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems. It included four Chinese databases [Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP) ], six English databases (Scopus, Embase, Web of Science, PubMed, Cochrane Library, and OpenGrey), and two registration systems (Chinese Clinical Trial Registry and ClinicalTrials.gov). The timeframe for the literature search extended from the inception of each database to December 31, 2023. Meta-analysis was performed using RevMan (v5.4.1), and the outcome indicators (pain relief rate, analgesic duration, quality of life, pain intensity, breakthrough pain frequency, and adverse reactions) were graded using GRADE profiler (v3.6). [Results] : According to the established inclusion and exclusion criteria, a total of 43 studies was deemed eligible, involving 3 142 participants with CIBP. The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone, the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate [risk ratio (RR) = 1.32, 95% confidence interval (CI): 1.24 to 1.41, P < 0.000 01], analgesic duration [mean difference (MD) = 1.33, 95% CI: 0.97 to 1.69, P < 0.000 01], and quality of life (MD = 5.66, 95% CI: 4.88 to 6.44, P < 0.000 01). Furthermore, the combined therapy significantly reduced pain intensity (MD = – 1.00, 95% CI: – 1.19 to – 0.80, P < 0.000 01), breakthrough pain frequency (MD = – 0.43, 95% CI: – 0.51 to – 0.36, P < 0.000 01), and adverse reactions (RR = 0.60, 95% CI: 0.53 to 0.68, P < 0.000 01) in CIBP patients. Based on the GRADE assessment, the level of evidence varied from low to moderate. [Conclusion] EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life. Additionally, the EA-TCM can effectively reduce the incidence of adverse reactions associated with three-step analgesic therapy.

Bone metastasis-caused pain （BMP） is a common complication of cancer， and the incidence has been on the rise with the increase in the overall prevalence of cancer， threatening the survival and quality of life of patients. BMP is a kind of special pain with the characteristics of inflammatory pain and neuropathic pain， but is different from the two. Therefore， its pathogenesis is very complicated， and it is of great significance to understand the pathogenesis. The currently available studies mainly focused on osteoclast activation， changes in the bone microenvironment， glial cell activation， spinal cord neuron activation， and miRNA dysregulation. Modern therapies include the three-step analgesics， bisphosphonates， palliative radiotherapy， and interventional therapy for bone metastases， which show definite efficacy in short term. However， the long-term effect is unsatisfactory due to the adverse reactions， addiction， and drug resistance. Studies have shown that traditional Chinese medicine （TCM） has definite curative effect on BMP， which is safe， enhances efficacy， reduces toxicity， and boosts immunity. Moreover， it exerts the effect through multiple components， multiple targets， and multiple pathways. As a result， it has unique advantages in the prevention and treatment of BMP and has become a research focus. This paper summarizes the research on the pathogenesis of BMP， the intervention of TCM （compound Chinese medicine prescriptions， Chinese medicinals， and monomers from Chinese medicinals）， and the mechanisms of TCM， such as inhibiting osteoclast activation， glial cell activation， and spinal cord neuron activation， regulating pain mediators and abnormal expression of microRNA， and anti-tumor， which is expected to further clarify the pathogenesis of BMP and provide ideas and methods for the effective prevention and treatment of BMP with TCM.