The leading cause of many respiratory diseases is an ongoing and progressive inflammatory response. Traditionally, inflammatory lung diseases were studied primarily through animal models, cell cultures, and organoids. These technologies have certain limitations, despite their great contributions to the study of respiratory diseases. Precision-cut lung slices (PCLS) are thin, uniform tissue slices made from human or animal lung tissue and are widely used extensively both nationally and internationally as an in vitro organotypic model. Human lung slices bridge the gap between in vivo and in vitro models, and they can replicate the living lung environment well while preserving the lungs’ basic structures, such as their primitive cells and trachea. However, there is no perfect model that can completely replace the structure of the human lung, and there is still a long way to go in the research of lung slice technology. This review details and analyzes the strengths and weaknesses of precision lung slices as an in vitro model for exploring respiratory diseases associated with inflammation, as well as recent advances in this field.

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.

This narrative review aims to explore research advances in multimodal rehabilitation for advanced cancer pain, with a primary focus on nonpharmacological intervention approaches, to offer comprehensive treatment strategies for cancer pain management. While the WHO analgesic regimen holds a central position, long-term medication use may lead to drug resistance and side effects. Nonpharmacological interventions have shown potential as effective adjuncts to pharmacological treatments, particularly in reducing medication side effects and enhancing patients' quality of life. Disparities in access, cultural acceptability, and cost-effectiveness-especially in low- and middle-income countries(LMICs)-along with publication bias and study heterogeneity remain significant challenges. Emerging technologies such as virtual reality and artificial-intelligence-driven applications show promise in addressing coverage gaps. Based on the comprehensive review of current evidence, multimodal rehabilitation incorporating nonpharmacological strategies-such as physical therapy, exercise training, psychological interventions, and complementary therapies-effectively complements pharmacologic management in alleviating advanced cancer pain and enhancing quality of life. Future efforts should focus on standardizing interventions, expanding access, and integrating these approaches within multidisciplinary frameworks to optimize pain control and functional outcomes.

Cancer pain is the most prevalent symptom experienced by cancer patients. It substantially impacts a patient’s long-term physical and emotional health, making it a pressing issue that must be addressed. Purinergic receptor P2X7 (P2X7R) is a widely distributed and potent non-selective ATP-gated ion channel that regulates tumor proliferation, chronic pain, and the formation of inflammatory lesions in the central nervous system. P2X7R plays an essential role in cancer pain and complications related to cancer pain including depression and opioid tolerance. This review focuses on the structure and distribution of P2X7R, its role in diverse tissues in cancer pain, and the application of P2X7R antagonists in the treatment of cancer pain to propose new ideas for cancer pain management.

Pain is a very common and complex medical problem that has a serious impact on individuals’ physical and mental health as well as society. Non-steroidal anti-inflammatory drugs and opioids are currently the main drugs used for pain management, but they are not effective in controlling all types of pain, and their long-term use can cause adverse effects that significantly impair patients’ quality of life. Mesenchymal stem cells (MSCs) have shown great potential in pain treatment. However, limitations such as the low proliferation rate of MSCs in vitro and low survival rate in vivo restrict their analgesic efficacy and clinical translation. In recent years, researchers have explored various innovative approaches to improve the therapeutic effectiveness of MSCs in pain treatment. This article reviews the latest research progress of MSCs in pain treatment, with a focus on methods to enhance the analgesic efficacy of MSCs, including engineering strategies to optimize the in vitro culture environment of MSCs and to improve the in vivo delivery efficiency of MSCs. We also discuss the unresolved issues to be explored in future MSCs and pain research and the challenges faced by the clinical translation of MSC therapy, aiming to promote the optimization and clinical translation of MSC-based analgesia therapy. Graphical Abstract

Bone cancer pain (BCP) is a severe complication in patients with advanced cancer, for which current therapies remain inadequate and often lead to significant adverse effects. Mesenchymal stromal cell (MSC)-based therapy has recently emerged as a promising strategy for pain management. However, the safety profile of MSC therapy for BCP treatment has not yet been verified in preclinical studies. In this study, clinical-grade human umbilical cord-derived MSCs (hUC-MSCs) at doses of 1 × 10⁶ or 4 × 10⁶ were administered intrathecally to BCP rats to evaluate analgesic efficacy, acute toxicity, and in vivo biodistribution. Additional assessments in nude mice investigated the tumorigenicity and tumor-promoting potential of hUC-MSCs. Intrathecal administration of hUC-MSCs effectively alleviated mechanical allodynia, heat hyperalgesia, spontaneous flinching, and gait abnormalities in BCP rats, while attenuating hyperactivation of neurons and glial cells in the spinal dorsal horn. The higher dose of 4 × 10⁶ hUC-MSCs demonstrated superior analgesic efficacy compared to the 1 × 10⁶ dose. Importantly, comprehensive safety evaluations confirmed a favorable preclinical safety profile for intrathecal hUC-MSC administration, demonstrating absence of acute toxicity, restricted distribution, and no tumorigenicity or tumor-promoting potential. Intrathecal hUC-MSC therapy demonstrates marked analgesic efficacy and a favorable safety profile in BCP, showing strong potential for clinical translation. This preclinical study provides compelling evidence to support future clinical trials and therapeutic applications of hUC-MSC therapy for BCP.