A Wearable Thin-Film Hydrogel Laser for Functional Sensing on Skin.

Flexible photonics offers the possibility of realizing wearable sensors by bridging the advantages of flexible materials and photonic sensing elements. Recently, optical resonators have emerged as a tool to improve their oversensitivity by integrating with flexible photonic sensors. However, direct monitoring of multiple psychological information on human skin remains challenging due to the subtle biological signals and complex tissue interface. To tackle the current challenges, here, we developed a functional thin film laser formed by encapsulating liquid crystal droplet lasers in a flexible hydrogel for monitoring metabolites in human sweat (lactate, glucose, and urea). The three-dimensional cross-linked hydrophilic polymer serves as the adhesive layer to allow small molecules to penetrate from human tissue to generate strong light--matter interactions on the interface of whispering gallery modes resonators. Both the hydrogel and cholesteric liquid crystal microdroplets were modified specifically to achieve high sensitivity and selectivity. As a proof of concept, wavelength-multiplexed sensing and a prototype were demonstrated on human skin to detect human metabolites from perspiration. These results present a significant advance in the fabrication and potential guidance for wearable and functional microlasers in healthcare.

TGF-ß1 Inhibits Osteoclast Differentiation and Abnormal Angiogenesis in Intervertebral Disc Degeneration: Evidence from RNA Sequencing and Animal Studies.

OBJECTIVE: Mechanisms involved in developing intervertebral disc degeneration (IDD) are poorly understood, thus making developing effective therapies difficult. This study aimed to suggest a possible molecular mechanism, based on transcriptome sequencing-identified transforming growth factor (TGF-ß), underlying the effects on bone homeostasis in IDD. METHODS: A mouse model for IDD was established. Transcriptome sequencing of nucleus pulposus tissue from mice (n = 3) identified differentially expressed mRNAs and key genes impacting bone homeostasis. A protein-protein interaction network pinpointed core genes. GO and KEGG analysis revealed gene functions. Expression levels of TGF-ß1, tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were measured. Micro-CT evaluated vertebral structures and vascular imaging. Western Blot measured expression levels of Vegf, Opn, MMP3, and MMP13. Safranin O-Fast Green and TRAP staining were performed on intervertebral discs and endplates. RESULTS: Transcriptomic analysis found 1790 differentially expressed mRNAs in IDD mice. Twenty-eight genes related to bone homeostasis in IDD were identified. TGF-ß1 was confirmed as the core gene. GO and KEGG showed TGF-ß1 regulates osteoclast markers like CTSK and TRAP through pathways including NF-κB and MAPK. Experimental validation revealed lower TGF-ß1 expression in IDD mice than controls, and increased TRAP and CTSK expression. Micro-CT showed decreased bone mass and intervertebral disc space in IDD mice. Vascular imaging showed increased vascular volume in IDD cartilaginous endplates. Western blot displayed increased VEGF and OPN levels, but decreased MMP3 and MMP13 in IDD mice. Safranin O-fast green staining revealed severe IDD degeneration. However, TGF-ß1 injection improved bone parameters in IDD mice. In vitro experiments confirmed TGF-ß1 inhibits bone marrow macrophages differentiation into osteoclasts. CONCLUSION: From our data, we conclude that TGF-ß1 repressed osteoclast differentiation and aberrant bone-associated angiogenesis in cartilage endplates (EPs) to alleviate IDD, which may be instrumental for the therapeutic targeting of IDD.

Submonolayer biolasers for ultrasensitive biomarker detection.

Biomarker detection is key to identifying health risks. However, designing sensitive and single-use biosensors for early diagnosis remains a major challenge. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. Telecom optical fibers serve as distributed optical microcavities with high Q-factor, great repeatability, and ultralow cost, which enables whispering-gallery laser emission to detect biomarkers. It is found that the sensing performance strongly depends on the number of gain molecules. The submonolayer lasers obtained a six-order-of-magnitude improvement in the lower limit of detection (LOD) when compared to saturated monolayer lasers. We further achieve an ultrasensitive immunoassay for a Parkinson's disease biomarker, alpha-synuclein (α-syn), with a lower LOD of 0.32 pM in serum, which is three orders of magnitude lower than the α-syn concentration in the serum of Parkinson's disease patients. Our demonstration of submonolayer biolaser offers great potentials in high-throughput clinical diagnosis with ultimate sensitivity.

Contrast-enhanced ultrasonography for identifying acute kidney injury in brain-dead donors.

Background: Acute kidney injury (AKI) is frequently found in deceased donors; however, few studies have reported the use of imaging to detect and identify this phenomenon. The purpose of this study was to detect renal microcirculatory perfusion in brain-dead donors using contrast-enhanced ultrasonography (CEUS), investigate the value of CEUS in identifying AKI, and analyze the correlation between CEUS and preimplantation biopsy results and early post-transplant renal function of grafts. Methods: This prospective study recruited 94 kidneys from brain-dead donors (AKI =44, non-AKI =50) from August 2020 to November 2022. The inclusion criteria were age ≥18 years and brain death. The exclusion criteria encompassed donors maintained with extracorporeal membrane oxygenation (ECMO) and the presence of irregular kidney anatomy. The mean age of the donors was 45.1±10.4 [standard deviation (SD)] years, and the majority were male (86.2%). CEUS was performed prior to organ procurement, and time-intensity curves (TICs) were constructed. The time to peak (TTP) and peak intensity (PI) of kidney segmental artery (KA), kidney cortex (KC), and kidney medulla (KM) were calculated using TIC analysis. Results: Arrival time (AT) of KA (P<0.001) and TTP of kidney cortex (TTPKC) (P<0.001) of the non-AKI group were significantly shorter than those of the AKI group. The PI of the KA (P=0.003), KM (P=0.005), and kidney cortex (PIKC; P<0.001) of the non-AKI group were significantly higher than those of the AKI group. Multivariable logistic regression analysis showed that serum creatinine [odds ratio (OR) =1.06; 95% CI: 1.03-1.1; P<0.001], TTPKC (OR =1.38; 95% CI: 1.03-1.84; P=0.03), and PIKC (OR =0.95; 95% CI: 0.91-1; P=0.046) were the independent factors of AKI. The area under the receiver operating characteristic curve (AUC) for identifying AKI for TTPKC and PIKC was 0.73 and 0.71, respectively. TTPKC showed a weak correlation with interstitial fibrosis (r=0.23; P=0.03), PIKC showed a weak correlation with arterial intimal fibrosis ((r=-0.29; P=0.004) and arteriolar hyalinosis (r=-0.27; P=0.008), and PIKC showed the strongest correlation with eGFR on postoperative day 7 (r=-0.46; P=0.046) in the donor kidneys with AKI. Conclusions: CEUS can be used to identify AKI in brain-dead donors. Furthermore, there is a correlation between CEUS-derived parameters and pretransplant biopsy results and early preimplantation renal function of grafts.

Contrast-enhanced ultrasonography-based renal blood perfusion in brain-dead donors predicts early graft function.

PURPOSE: The aim of this study was to quantify renal microcirculatory perfusion in braindead donors using contrast-enhanced ultrasonography (CEUS), and to establish an accurate, noninvasive, and convenient index for predicting delayed graft function (DGF) post-transplantation. METHODS: In total, 90 brain-dead donor kidneys (training group, n=60; validation group, n=30) examined between August 2020 and November 2022 were recruited in this prospective study. CEUS was performed on the kidneys of brain-dead donors 24 hours before organ procurement and time-intensity curves were constructed. The main measures were arrival time, time to peak, and peak intensity of the kidney segmental arteries, cortex, and medulla. Recipients were divided into DGF and non-DGF groups according to early post-transplant graft function. The area under the receiver operating characteristic curve (AUC) was used to assess diagnostic performance. RESULTS: The arrival time of the kidney segmental artery and cortex and the time interval between the time to peak of the segmental artery and cortex were identified as independent factors associated with DGF by multivariate stepwise regression analysis. A new index for the joint prediction model of three variables, the contrast-enhanced ultrasonography/Kidney Donor Profile index (CEUS-KDPI), was developed. CEUS-KDPI showed high accuracy for predicting DGF (training group: AUC, 0.91; sensitivity, 90.5%; specificity, 92.3%; validation group: AUC, 0.84; sensitivity, 75.0%; specificity, 92.3%). CONCLUSION: CEUS-KDPI accurately predicted DGF after kidney transplantation. CEUS may be a potential noninvasive tool for bedside examinations before organ procurement and may be used to predict early renal function after kidney transplants kidneys from donors after brain death.

Roles of pyroptosis in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD), the key pathological process in low back pain, is characterized by chronic inflammation and progressive cell death. Pyroptosis is a type of pro-inflammatory programmed necrosis mediated by inflammasomes that is dependent on the gasdermin family of proteins. An in-depth study of the pathological mechanisms of IDD has revealed that pyroptosis plays an important role in its occurrence and development. The molecular characteristics and activation signaling mechanisms of pyroptosis are reviewed in this paper. Moreover, the specific roles of pyroptosis in IDD pathology are outlined and various targeted drugs for its treatment are highlighted.

Intrathecal Injection of Botulinum Toxin Type A has an Analgesic Effect in Male Rats CCI Model by Inhibiting the Activation of Spinal P2X4R.

Purinergic receptor P2X4 (P2X4R) plays an essential role in neuropathic pain. However, the specific mechanism needs to be clarified. Botulinum toxin type A is a neurotoxin produced by Clostridium botulinum type A. This study found that intrathecal injection of botulinum toxin type A produced an excellent analgesic effect in a rat model of chronic constriction sciatic nerve injury and inhibited the activation of P2X4R, microglia, and astrocytes. The administration of a P2X4R activator can up-regulate the expression of P2X4R and eliminate the analgesic effect of intrathecal injection of botulinum toxin type A. In addition, we found that microglia and astrocytes in the spinal cord of rats injected with botulinum toxin type A were reactivated after administration of the P2X4R activator. Our results suggest that intrathecal injection of botulinum toxin type A has an analgesic effect in a rat model of chronic constriction sciatic nerve injury by inhibiting the activation of P2X4R in the spinal cord.

Bibliometric and visual analysis of microglia-related neuropathic pain from 2000 to 2021.

Background: Microglia has gradually gained researchers' attention in the past few decades and has shown its promising prospect in treating neuropathic pain. Our study was performed to comprehensively evaluate microglia-related neuropathic pain via a bibliometric approach. Methods: We retrospectively reviewed publications focusing on microglia-related neuropathic pain from 2000 to 2021 in WoSCC. VOS viewer software and CiteSpace software were used for statistical analyses. Results: A total of 2,609 articles were finally included. A steady increase in the number of relevant publications was observed in the past two decades. China is the most productive country, while the United States shares the most-cited and highest H-index country. The University of London, Kyushu University, and the University of California are the top 3 institutions with the highest number of publications. Molecular pain and Pain are the most productive and co-cited journals, respectively. Inoue K (Kyushu University) is the most-contributed researcher and Ji RR (Duke University) ranks 1st in both average citations per article and H-index. Keywords analyses revealed that pro-inflammatory cytokines shared the highest burst strength. Sex differences, neuroinflammation, and oxidative stress are the emerging keywords in recent years. Conclusion: In the field of microglia-related neuropathic pain, China is the largest producer and the United States is the most influential country. The signaling communication between microglia and neurons has continued to be vital in this field. Sexual dimorphism, neuroinflammation, and stem-cell therapies might be emerging trends that should be closely monitored.

Intrathecal administration of botulinum toxin type a antagonizes neuropathic pain by countering increased vesicular nucleotide transporter expression in the spinal cord of chronic constriction injury of the sciatic nerve rats.

Botulinum toxin type A (BoNT/A) induces direct analgesic effects in neuropathic pain by inhibiting the release of substance P, calcitonin gene-related peptide (CGRP) and glutamate. Vesicular nucleotide transporter (VNUT) was responsible for the storage and release of ATP in vivo, and one of the mechanisms underlying neuropathic pain is VNUT-dependent release of extracellular ATP from dorsal horn neurons. However, the analgesic effect of BoNT/A by affecting the expression of VNUT remained largely unknown. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of BoNT/A in chronic constriction injury of the sciatic nerve (CCI) induced neuropathic pain. Our results showed that a single intrathecal injection of 0.1 U BoNT/A seven days after CCI surgery produced significant analgesic activity and decreased the expression of VNUT in the spinal cord of CCI rats. Similarly, BoNT/A inhibited the CCI-induced increase in ATP content in the rat spinal cord. Overexpression of VNUT in the spinal cord of CCI-induced rats markedly reversed the antinociceptive effect of BoNT/A. Furthermore, 33 U/mL BoNT/A dramatically reduced the expression of VNUT in pheochromocytoma (PC12) cells but overexpressing SNAP-25 increased VNUT expression in PC12 cells. Our current study is the first to demonstrate that BoNT/A is involved in neuropathic pain by regulating the expression of VNUT in the spinal cord in rats.

Autonomous Microlasers for Profiling Extracellular Vesicles from Cancer Spheroids.

Self-propelled micro/nanomotors are emergent intelligent sensors for analyzing extracellular biomarkers in circulating biological fluids. Conventional luminescent motors are often masked by a highly dynamic and scattered environment, creating challenges to characterize biomarkers or subtle binding dynamics. Here we introduce a strategy to amplify subtle signals by coupling strong light-matter interactions on micromotors. A smart whispering-gallery-mode microlaser that can self-propel and analyze extracellular biomarkers is demonstrated through a liquid crystal microdroplet. Lasing spectral responses induced by cavity energy transfer were employed to reflect the abundance of protein biomarkers, generating exclusive molecular labels for cellular profiling of exosomes derived from 3D multicellular cancer spheroids. Finally, a microfluidic biosystem with different tumor-derived exosomes was employed to elaborate its sensing capability in complex environments. The proposed autonomous microlaser exhibits a promising method for both fundamental biological science and applications in drug screening, phenotyping, and organ-on-chip applications.

Motor-like microlasers functioning in biological fluids.

Microlasers integrated with biological systems have received tremendous attention for their intense light intensity and narrow linewidth recently, serving as a powerful tool for studying complex dynamics and interactions in scattered biological micro-environments. However, manipulation of microlasers with controllable motions and versatile functions remains elusive. Herein, we introduce the concept of motor-like microlasers formed by magnetic-doped liquid crystal droplets, in which the direction and velocity could be controlled by altering internal magnetic nanoparticles or external magnetic fields. Both translational and rotatory motions of the lasing resonator could be continually changed in real-time. Lasing-encoded motors carrying different functions and lasing wavelengths were also achieved. Finally, we demonstrate the potential of motor-like microlasers by functioning as a localized stimulation emission light source to stimulate or illuminate living cells, providing a novel approach for switching on/off light emissions and subcellular imaging. Laser emitting micromotors offer a facile system for precise manipulation of microlasers in biological fluids, providing new insight into the development of programmable on-chip laser devices and laser-emitting intelligent systems.

Long non­coding RNA PART1: dual role in cancer.

Increasing evidence has shown that long non-coding RNAs (lncRNAs), which are non-coding endogenous single-stranded RNAs, play an essential role in various physiological and pathological processes through transcriptional interference, post-transcriptional regulation, and epigenetic modification. Moreover, lncRNAs, as oncogenes or tumor suppressor genes, play an important role in the occurrence and development of human cancers. Prostate androgen-regulated transcript 1 (PART1) was initially identified as a carcinogenic lncRNA in prostate adenomas. The upregulated expression of PART1 plays a tumor-promoting role in liver, prostate, lung cancers, and other tumors. In contrast, the expression of PART1 is downregulated in esophageal squamous cell carcinoma, glioma, and other tumors, which may inhibit the tumor. PART1 plays a dual role in cancer and regulates cell proliferation, apoptosis, invasion, and metastasis through a variety of potential mechanisms. These findings suggest that PART1 is a promising tumor biomarker and therapeutic target. This article reviews the biological functions, related mechanisms, and potential clinical significance of PART1 in a variety of human cancers.

Mechanisms and functions of long noncoding RNAs in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a key pathological process underlying low back pain. Although, to date, specific molecular mechanisms have not been elucidated, at the cellular level, it is mainly due to pathological changes in the life process of nucleus pulposus (NP) cells in the intervertebral disc (IVD). These changes are closely related to cell proliferation, apoptosis, senescence, autophagy, inflammation, and extracellular matrix (ECM) remodeling. Long noncoding RNAs (lncRNAs) have gradually become a focus of scientific research because of their functional complexity and local tissue specific expression. Moreover, they mediate a series of cellular signaling pathways in NP cells by competing for microRNA (miRNA) or directly targeting gene expression by mRNA adsorption, thereby regulating cell life activities that play a vital role in the mechanism underlying IDD. In-depth studies on lncRNAs can help identify new therapeutic targets or aid in developing IDD treatment strategies at the gene level and those based on regenerative medicine, thus providing new ideas for researchers. This article reviews the classification, biological functions, mechanisms of action, and therapeutic potential of lncRNAs in IDD.

Hollow Hemispherical Lithium Iron Silicate Synthesized by an Ascorbic Acid-Assisted Hydrothermal Method as a Cathode Material for Li Ion Batteries.

High-capacity and high-voltage cathode materials are required to meet the increasing demand for energy density in Li ion batteries. Lithium iron silicate (Li2FeSiO4) is a cathode material with a high theoretical capacity of 331 mAh·g-1. However, its poor conductivity and low Li ion diffusion coefficient result in poor capability, hindering practical applications. Morphology has an important influence on the properties of materials, and nanomaterials with hollow structures are widely used in electrochemical devices. Herein, we report a novel hollow hemispherical Li2FeSiO4 synthesized by a template-free hydrothermal method with the addition of ascorbic acid. The hollow hemispherical Li2FeSiO4 consisted of finer particles with a shell thickness of about 80 nm. After carbon coating, the composite was applied as the cathode in Li ion batteries. As a result, the hollow hemispherical Li2FeSiO4/C exhibited a discharge capacity as high as 192 mAh·g-1 at 0.2 C, and the average capacities were 134.5, 115.5 and 93.4 mAh·g-1 at 0.5, 1 and 2 C, respectively. In addition, the capacity increased in the first few cycles and then decayed with further cycling, showing a warm-up like behavior, and after 160 cycles the capacities maintained 114.2, 101.6 and 79.3 mAh·g-1 at 0.5, 1 and 2 C, respectively. Such a method of adding ascorbic acid in the hydrothermal reaction can effectively synthesize hollow hemispherical Li2FeSiO4 with the enhanced electrochemical performance.

Multicolor Light Mixing in Optofluidic Concave Interfaces for Anticounterfeiting with Deep Learning Authentication.

Anticounterfeiting technology has received tremendous interest for its significance in daily necessities, medical industry, and high-end products. Confidential tags based on photoluminescence are one of the most widely used approaches for their vivid visualization and high throughput. However, the complexity of confidential tags is generally limited to the accessibility of inks and their spatial location; generating an infinite combination of emission colors is therefore a challenging task. Here, we demonstrate a concept to create complex color light mixing in a confined space formed by microscale optofluidic concave interfaces. Infinite color combination and capacity were generated through chaotic behavior of light mixing and interaction in an ininkjet-printed skydome structure. Through the chaotic mixing of emission intensity, wavelength, and light propagation trajectories, the visionary patterns serve as a highly unclonable label. Finally, a deep learning-based machine vision system was built for the authentication process. The developed anticounterfeiting system may provide inspiration for utilizing space color mixing in optical security and communication applications.

Cellular Features Revealed by Transverse Laser Modes in Frequency Domain.

Biological lasers which utilize Fabry-Pérot (FP) cavities have attracted tremendous interest due to their potential in amplifying subtle biological changes. Transverse laser modes generated from cells serve as distinct fingerprints of individual cells; however, most lasing signals lack the ability to provide key information about the cell due to high complexity of transverse modes. The missing key, therefore, hinders it from practical applications in biomedicine. This study reveals the key mechanism governing the frequency distributions of transverse modes in cellular lasers. Spatial information of cells including curvature can be interpreted through spectral information of transverse modes by means of hyperspectral imaging. Theoretical studies are conducted to explore the correlation between the cross-sectional morphology of a cell and lasing frequencies of transverse modes. Experimentally, the spectral characteristics of transverse modes are investigated in live and fixed cells with different morphological features. By extracting laser modes in frequency domain, the proposed concept is applied for studying cell adhesion process and cell classification from rat cortices. This study expands a new analytical dimension of cell lasers, opening an avenue for subcellular analysis in biophotonic applications.

Tunable Optical Vortex from a Nanogroove-Structured Optofluidic Microlaser.

Optical vortices with tunable properties in multiple dimensions are highly desirable in modern photonics, particularly for broadly tunable wavelengths and topological charges at the micrometer scale. Compared to solid-state approaches, here we demonstrate tunable optical vortices through the fusion of optofluidics and vortex beams in which the handedness, topological charges, and lasing wavelengths could be fully adjusted and dynamically controlled. Nanogroove structures inscribed in Fabry-Pérot optofluidic microcavities were proposed to generate optical vortices by converting Hermite-Gaussian laser modes. Topological charges could be controlled by tuning the lengths of the nanogroove structures. Vortex laser beams spanning a wide spectral band (430-630 nm) were achieved by alternating different liquid gain materials. Finally, dynamic switching of vortex laser wavelengths in real-time was realized through an optofluidic vortex microlaser device. The findings provide a robust yet flexible approach for generating on-chip vortex sources with multiple dimensions, high tunability, and reconfigurability.

Liquid crystal-amplified optofluidic biosensor for ultra-highly sensitive and stable protein assay.

Protein assays show great importance in medical research and disease diagnoses. Liquid crystals (LCs), as a branch of sensitive materials, offer promising applicability in the field of biosensing. Herein, we developed an ultrasensitive biosensor for the detection of low-concentration protein molecules, employing LC-amplified optofluidic resonators. In this design, the orientation of LCs was disturbed by immobilized protein molecules through the reduction of the vertical anchoring force from the alignment layer. A biosensing platform based on the whispering-gallery mode (WGM) from the LC-amplified optofluidic resonator was developed and explored, in which the spectral wavelength shift was monitored as the sensing parameter. The microbubble structure provided a stable and reliable WGM resonator with a high Q factor for LCs. It is demonstrated that the wall thickness of the microbubble played a key role in enhancing the sensitivity of the LC-amplified WGM microcavity. It is also found that protein molecules coated on the internal surface of microbubble led to their interactions with laser beams and the orientation transition of LCs. Both effects amplified the target information and triggered a sensitive wavelength shift in WGM spectra. A detection limit of 1 fM for bovine serum albumin (BSA) was achieved to demonstrate the high-sensitivity of our sensing platform in protein assays. Compared to the detection using a conventional polarized optical microscope (POM), the sensitivity was improved by seven orders of magnitude. Furthermore, multiple types of proteins and specific biosensing were also investigated to verify the potential of LC-amplified optofluidic resonators in the biomolecular detection. Our studies indicate that LC-amplified optofluidic resonators offer a new solution for the ultrasensitive real-time biosensing and the characterization of biomolecular interactions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43074-021-00041-1.

Self-Assembled Biophotonic Lasing Network Driven by Amyloid Fibrils in Microcavities.

Self-assembled biological structures have played a significant role in many living systems for its functionality and distinctiveness. Here, we experimentally demonstrate that the random dynamic behavior of strong light-matter interactions in complex biological structures can provide hidden information on optical coupling in a network. The concept of biophotonic lasing network is therefore introduced, where a self-assembled human amyloid fibril network was confined in a Fabry-Perot optical cavity. Distinctive lasing patterns were discovered from self-assembled amyloids with different structural dimensions (0D, 1D, 2D, and 3D) confined in a microcavity. Network laser emission exhibiting evidence of light coupling at different wavelengths and locations was spectrally resolved. Dynamic changes of lasing patterns can therefore be interpreted into a graph to reveal the optical correlation in biophotonic networks. Our findings indicate that each graph represents the highly unclonable features of a self-assembled network which can sensitively respond to environmental stimulus. This study offers the potential for studying dynamic biological networks through amplified interactions, shedding light on the development of biologically controlled photonic devices, biosensing, and information encryption.

Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism.

Cancer pain is one of the main complications in advanced cancer patients, and its management is still challenging. Therefore, there is an urgent need to develop novel pharmacotherapy for cancer pain. Several natural products have attracted the interest of researchers. In previous studies, curcumin has proved to exhibit antitumor, antiviral, antioxidant, anti-inflammatory, and analgesic effects. However, the analgesic mechanism of curcumin has not been elucidated. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of curcumin in cancer-induced bone pain. Our results showed that consecutive curcumin treatment (30, 60, 120 mg/kg, i.p., twice daily for 11 days) produced significant analgesic activity, but had no effect on the progress of the bone cancer pain. Notably, pretreatment with naloxone, a non-selective opioid receptor antagonist, markedly reversed the antinociceptive effect induced by curcumin. Moreover, in primary cultured rat dorsal root ganglion (DRG) neurons, curcumin significantly up-regulated the expression of proopiomelanocortin (Pomc) and promoted the release of ß-endorphin and enkephalin. Furthermore, pretreatment with the antiserum of ß-endorphin or enkephalin markedly attenuated curcumin-induced analgesia in cancer-induced bone pain. Our present study, for the first time, showed that curcumin attenuates cancer-induced bone pain. The results also suggested that stimulation of expression of DRG neurons ß-endorphin and enkephalin mediates the antinociceptive effect of curcumin in pain hypersensitivity conditions.