Cancer pain is a common and severe complication of human breast cancer, and relieving pain is fundamental strategy in the treatment. Fentanyl, as an opioid analgesic, is widely used in breast cancer patients. However, little is known about its effects on stemness and epithelial-mesenchymal transition (EMT) of breast cancer cells. Aberrant protein glycosylation is involved in cancer malignancy. The α1, 6-fucosylation is an important type of glycosylation, and the elevated α1, 6-fucosylation catalyzed by fucosyltransferase Ⅷ (FUT8) is found in many tumors. However, whether 1, 6-fucosylation is involved in regulating stemness and EMT, and stimulated by fentanyl is not clear. In this study, we found that fentanyl induced stemness and EMT in MCF-7 and MDA-MB-231 breast cancer cells by analysis of sphere formation, expression of stemness markers (Sox2, Oct4) and EMT markers (N-cadherin, E-cadherin and Vimentin). Results also showed that fentanyl upregulated FUT8 gene and protein expression by qPCR, Western blot and immunofluorescent staining, as well as α1, 6-fucosylation level by Lectin blot and Lectin fluorescent staining. Furthermore, decreased or blocked α1, 6-fucosylation by FUT8 siRNA transfection or LCA Lectin blockage reduced stemness and EMT. Additionally, fentanyl activated the key molecules and target genes in Wnt/β-catenin signaling pathway. LGK-974 (an inhibitor of Wnt ligands) suppressed fentanyl-mediated upregulation of α1, 6-fucosylation, stemness and EMT. The results of tumor xenograft demonstrated that fentanyl enhanced tumor growth, α1, 6-fucosylation, stemness and EMT. Taken together, our study reveals that fentanyl upregulated FUT8 expression, which increased α1, 6-fucosylation level through activation of Wnt/β-catenin signaling pathway, thereby, induce stemness and EMT of breast cancer cells. This study suggest a potential side effect of fentanyl in the treatment of cancer, which may guide the safety of fentanyl in the clinical application.

Postoperative pain is one of the most prevalent complications following surgery, and more than 47% of surgical patients endure postoperative discomfort worldwide. In Africa, due to resource shortages and other issues, postoperative pain is substantially more common when compared to developed countries. Severe postoperative pain has many negative effects, including possibly death, which can burden both individuals and society as a whole. Therefore, effectively controlling postoperative pain is becoming increasingly important. To enhance the effectiveness of future pain management, a thorough analysis of the current reasons for inadequate postoperative pain management is necessary. In this article, the present situations of occurring postoperative pain, children’s postoperative pain, and pain management in Africa are reviewed, based on relevant and recent literature. In particular, the reasons for inadequate postoperative pain management in Africa are detailed in this article from five perspectives: the inadequate assessment of postoperative pain, the knowledge gap among medical professionals, the patients’ misconceptions, the scarcity of resources, and the lack of medications. Additionally, we offer appropriate solutions following various factors.

Background: The transition from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype presents a novel therapeutic strategy for chronic pain. Objective: We investigated the role of microglia polarization in cancer-induced bone pain (CIBP), as well as the role of the P2X7 receptor in modulating M1 to M2 polarization. Methods: Walker-256 breast cancer cells were administered into tibias of female rats to induce bone cancer–associated cancer. Results: During bone cancer development, the P2X7 receptor and M1 microglia markers were upregulated. In contrast, inhibition of the P2X7 receptor by BBG, a blood-brain barrier-permeable P2X7R-specific antagonist, alleviated the pain and promoted microglia polarization toward the M2 phenotype, while suppressing the M1 phenotype in vivo and in vitro. Conclusion: P2X7 receptor-mediated spinal microglia polarization is involved in alleviation of CIBP. Therefore, P2X7R is a potential option for CIBP treatment.

Acupuncture is an ancient Chinese technique, developed over >3,000 years, in which ʻacupointsʼ are stimulated with the aim of treating various diseases. A number of previous studies have indicated that acupuncture may play a role in inducing analgesia. Acupuncture‑induced analgesia has been hypothesized to act on various parts of the central nervous system, including the spinal cord, brain stem, cerebral ganglia and cerebral cortex. The mechanisms underlying the effects of acupuncture have been purported to include neurohumors and neurotransmitters, such as opioids and γ‑aminobutyric acid, signaling pathways and the immune response, which are all involved in the induction of analgesia.

Autophagy is a critical cellular adaptive response in tumor formation. Nutritional deficiency and hypoxia exacerbate autophagic flux in established malignancies, promoting tumor cell proliferation, migration, metastasis, and resistance to therapeutic interventions. Pro-survival autophagy inhibition may be a promising treatment option for advanced cancer. Furthermore, excessive or persistent autophagy is cytotoxic, resulting in tumor cell death. Targeted autophagy activation has also shown significant promise in the fight against tumor drug resistance. Several research groups have examined the ability of natural products (NPs) such as alkaloids, terpenoids, polyphenols, and anthraquinones to serve as autophagy inhibitors or activators. The data support the capacity of NPs that promote lethal autophagy or inhibit pro-survival autophagy from being employed against tumor drug resistance. This paper discusses the potential applications of NPs that regulate autophagy in the fight against tumor drug resistance, some limitations of the current studies, and future research needs and priorities.

Neuropathic pain is a chronic pain condition caused by damage to the nervous system. Its pathogenesis is complex, and effective treatments are limited, significantly impairing patients' quality of life. Mitochondria are the energy supply centers of cells and play a crucial role in maintaining neuronal homeostasis. Growing evidence suggests mitochondrial dysfunction is a key contributor to pain initiation and persistence. However, the role of mitochondrial dysfunction in neuropathic pain has been relatively less studied, and its underlying mechanisms remain unclear. This article reviews the latest research progress on the mechanisms by which mitochondrial dysfunction affects neuropathic pain, with a focus on key pathways including mitochondrial morphological alterations, bioenergetic abnormalities (such as reduced adenosine triphosphate production and decreased membrane potential), dynamic impairments (e.g., disrupted axonal transport, mitochondrial fragmentation, and calcium homeostasis imbalance), enhanced oxidative stress, and impaired mitochondrial autophagy. These mechanisms collectively contribute to neuronal dysfunction and abnormal transmission of pain signals. Additionally, this article elaborates on various therapeutic strategies targeting mitochondrial dysfunction, offering novel insights and scientific evidence for the precise treatment of neuropathic pain.