Huan-Jun Lu

To elucidate the role and underlying mechanism of bradykinin (BK) B2 receptor and its downstream inositol 1,4,5-trisphosphate receptor type 1 (ITPR1)-mediated endoplasmic reticulum (ER) calcium release signaling in the development and maintenance of trigeminal neuropathic pain. A partial infraorbital nerve transection (pIONT) mouse model of trigeminal neuralgia was employed. Mechanical allodynia was assessed using von Frey filaments. The expression and localization of BK, B2 receptor, and related molecules in the trigeminal ganglion (TG) were analyzed by quantitative real-time PCR (qPCR), Western blot, and immunofluorescence staining. Whole-cell patch-clamp recordings were performed to evaluate TG neuronal excitability. Intracellular calcium signals induced by BK were monitored through Fluo-4 AM calcium imaging. Pharmacological and genetic interventions were conducted via local TG injection of B2 receptor antagonist Icatibant, ITPR1 inhibitor 2-APB, and Itpr1-siRNA. pIONT induced persistent facial mechanical allodynia in mice, accompanied by a significant upregulation of BK mRNA and B2 receptor expression in the TG, which was primarily localized to myelinated neurons (NF200+), peptidergic neurons (CGRP+), and non-peptidergic neurons (IB4+). Local injection of Icatibant into the TG significantly alleviated mechanical nociceptive responses and reduced the hyperexcitability of nociceptive neurons. Calcium imaging showed that BK evoked ITPR1-dependent ER calcium release in TG neurons, which was abolished by both 2-APB and Itpr1-siRNA. Co-application of 2-APB also reversed BK-induced neuronal hyperexcitability and attenuated facial withdrawal responses. Following peripheral nerve injury, the B2 receptor-ITPR1 signaling mediated ER calcium release represents an essential mechanism underlying the development and maintenance of trigeminal neuropathic pain. Targeting this signaling pathway effectively attenuates peripheral neuronal hyperexcitability, providing novel experimental evidence and potential therapeutic targets for the management of trigeminal neuralgia.

Endoplasmic reticulum (ER) stress has emerged as a key player in the development of diverse chronic pain disorders; however, its specific contribution to m

Endoplasmic reticulum (ER) stress has been implicated in various chronic pain conditions, but its role in trigeminal neuropathic pain (TNP) remains unclear

Tenascin-C (TNC) is a complex extracellular matrix (ECM) protein that plays a critical role in regulating cellular adhesion, motility, proliferation, and inflammation through its interaction with Toll-like receptor 4 (TLR4) and other receptors. The upregulation of TNC is associated with inflammatory responses, autoimmune disorders, and neoplastic conditions during both physiological and pathological tissue remodeling. In the central nervous system (CNS), TNC contributes to neuroinflammatory processes by modulating the function of immune cells and the secretion of pro-inflammatory mediators, thereby playing a pivotal role in the initiation and progression of neuroinflammatory diseases. TNC is expressed in astrocytes, neural progenitor cells, and various neuronal populations within both developing and mature CNS regions. It regulates neuronal migration and axonal guidance during neurogenesis, facilitating synaptic plasticity and CNS regeneration. Furthermore, TNC enhances neuroplasticity through interactions with receptor families, such as integrins, to establish the molecular connections necessary for cell communication and signal transduction. This review investigates the mechanistic properties of TNC, focusing on its spatiotemporal expression, molecular interactions with receptors, and its role in neurological disorders, in addition to its modulatory capacity in neuroplastic processes. Additionally, this review delves into recent research advancements with respect to neuroinflammation involving TNC, along with therapeutic strategies targeting TNC.

Lysosomes are highly dynamic organelles that maintain cellular homeostasis and regulate fundamental cellular processes by integrating multiple metabolic pathways. Lysosomal ion channels such as TRPML1-3, TPC1/2, ClC6/7, CLN7, and TMEM175 mediate the flux of Ca²⁺, Cl⁻, Na⁺, H⁺, and K⁺ across lysosomal membranes in response to osmotic stimulus, nutrient-dependent signals, and cellular stresses. These ion channels serve as the crucial transducers of cell signals and are essential for the regulation of lysosomal biogenesis, motility, membrane contact site formation, and lysosomal homeostasis. In terms of pathophysiology, genetic variations in these channel genes have been associated with the development of lysosomal storage diseases, neurodegenerative diseases, inflammation, and cancer. This review aims to discuss the current understanding of the role of these ion channels in the central nervous system and to assess their potential as drug targets.

Nanoparticle delivery of functional molecules or vaccines is an effective method for the treatment of many diseases. This study aims to design ginsenoside Rh2-conjugated O-carboxymethyl chitosan (O-CMC/Rh2) as a drug delivery system and explore its anti-nociceptive effects. O-CMC/Rh2 was synthesized with an esterification reaction, and its chemical composition and morphology were evaluated using proton nuclear magnetic resonance (¹H NMR), the attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and scanning electron microscopy (SEM). In addition, the in vitro cumulative release of Rh2 from the O-CMC/Rh2 was also evaluated under different pH conditions. The results showed that the ginsenoside Rh2 was successfully conjugated to the O-CMC matrix and exhibited a highly porous structure after conjugation, facilitating the release of Rh2 from O-CMC. Complete Freund’s adjuvant (CFA) and burn injury-induced pain models were used to evaluate the anti-nociceptive effects of O-CMC/Rh2 on inflammatory pain. O-CMC/Rh2 reduced CFA-induced pain hypersensitivity in a dose-dependent manner and had a longer analgesic effect than Rh2. In addition, O-CMC/Rh2 also relieved the chronic pain induced by bury injury. These results indicated that O-CMC/Rh2 could be useful in reducing inflammatory pain, thus possessing a potential medicinal application in pain therapy.

Cancer-induced bone pain (CIBP) caused by bone metastasis is one of the most prevalent diseases, and current treatments rely primarily on opioids, which have significant side effects. However, recent developments in pharmaceutical science have identified several new mechanisms for CIBP, including the targeted modification of certain ion channels and receptors. Ion channels are transmembrane proteins, which are situated on biological cell membranes, which facilitate passive transport of inorganic ions across membranes. They are involved in various physiological processes, including transmission of pain signals in the nervous system. In recent years, there has been an increasing interest in the role of ion channels in chronic pain, including CIBP. Therefore, in this review, we summarize the current literature on ion channels, related receptors, and drugs and explore the mechanism of CIBP. Targeting ion channels and regulating their activity might be key to treating pain associated with bone cancer and offer new treatment avenues.

Highlights: • The commonly used synthetic polymers for vascular grafts are reviewed.• Various methods for surface modification of artificial vascular grafts are summarized.• Latest fabrication techniques for small-diameter vascular grafts and their mechanical and biological properties are systematically summarized.• Current state and future perspective of small-diameter vascular grafts are suggested.