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Pain Sensitivity Genes as Therapeutic Targets in Knee Osteoarthritis: A Comprehensive Analysis Mol. Pain (IF 2.8) Pub Date : 2024-09-24 Zirui Li, Haicheng Chen, Chujie Chen
Pain sensitivity is a significant factor in knee osteoarthritis (KOA), influencing patient outcomes and complicating treatment. Genetic differences, particularly in pain-sensing genes (PSRGs), are known to contribute to the variability in pain experiences among KOA patients. This study aims to systematically analyze PSRGs in KOA to better understand their role and potential as therapeutic targets.
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Characteristics of Immune Cells and Causal Relationship with Chondromalacia: A Two-Sample, Bidirectional Mendelian Randomization Study Mol. Pain (IF 2.8) Pub Date : 2024-09-24 Weiwei Chai, Mengwei Zhang, Yan He, Weihao Chai
Chondromalacia, characterized by the softening of cartilage, is a prevalent condition affecting joint health with complex etiology. The immune system's role in its pathogenesis has been implicated but remains to be fully elucidated. To address a critical knowledge gap, we conducted a two-sample Mendelian randomization analysis of 731 immune cell phenotypes, assessing parameters like fluorescence, cell
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Neural Adaptation of the Reward System in Primary Dysmenorrhea Mol. Pain (IF 2.8) Pub Date : 2024-09-14 Pei-Shan Hsu, Ching-Hsiung Liu, Ching-Ju Yang, Lin-Chien Lee, Wei-Chi Li, Hsiang-Tai Chao, Li-Fen Chen, Jen-Chuen Hsieh
Introduction The brain's reward system (RS) reacts differently to pain and its alleviation. This study examined the correlation between RS activity and behavior during both painful and pain-free periods in individuals with primary dysmenorrhea (PDM) to elucidate their adaptive and maladaptive responses throughout the menstrual cycle. Methods Ninety-two individuals with PDM and 90 control participants
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Rapid cleavage of IL-1β in DRG neurons produces tissue injury-induced pain hypersensitivity Mol. Pain (IF 2.8) Pub Date : 2024-09-06 Daisuke Fujita, Yutaka Matsuoka, Shunsuke Yamakita, Yasuhiko Horii, Daiki Ishikawa, Kohsuke Kushimoto, Hiroaki Amino, fumimasa amaya
Background IL-1β plays a critical role in the pathophysiology of neuroinflammation. The presence of cleaved IL-1β (cIL-1β) in the neurons of the dorsal root ganglion (DRG) implicates its function in biological signaling arising from the sensory neuron. This study was conducted to analyze the role of IL-1β in nociceptive transduction after tissue injury. Methods A plantar incision was made in C57BL/6
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Mechanical and cold polymodality coexist in tactile peripheral afferents, and it's not mediated by TRPM8. Mol. Pain (IF 2.8) Pub Date : 2024-08-07 M. Danilo Boada, Silvia Gutierrez
In the mammalian somatosensory system, polymodality is defined as the competence of some neurons to respond to multiple forms of energy (e.g., mechanical and thermal). This ability is thought to be an exclusive property of nociceptive neurons (polymodal C-fiber nociceptors) and one of the pillars of nociceptive peripheral plasticity. The current study uncovered a completely different neuronal sub-population
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rs12411980 single-nucleotide polymorphism related to PRTFDC1 expression is significantly associated with phantom tooth pain Mol. Pain (IF 2.8) Pub Date : 2024-08-02 Jun Araida, Seii Ohka, Moe Soeda, Daisuke Nishizawa, Junko Hasegawa, Kyoko Nakayama, Yuko Ebata, Yasukazu Ogai, Ken-ichi Fukuda, Kazutaka Ikeda
Phantom tooth pain (PTP) is one type of non-odontogenic neuropathic toothache, which rarely occurs after appropriate pulpectomy or tooth extraction. The cause of PTP is unknown. We investigated pain-related genetic factors that are associated with PTP. Four pain-associated genes, including G protein-coupled receptor 158 ( GPR158) and phosphoribosyl transferase domain containing 1 ( PRTFDC1), are adjacent
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The Analgesic Effects of Botulinum Neurotoxin by Modulating Pain-Related Receptors; A Literature Review Mol. Pain (IF 2.8) Pub Date : 2024-08-02 maziyar askari rad, saereh hosseindost, Seyed Hassan inanloo, Mojgan Rahimi, Samaneh Dehghan, Amirhossein Orandi, Ahmad Reza Dehpour, hossein majedi
Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, have been used for the treatment of various central and peripheral neurological conditions. Recent studies have suggested that BoNTs may also have a beneficial effect on pain conditions. It has been hypothesized that one of the mechanisms underlying BoNTs' analgesic effects is the inhibition of pain-related receptors' transmission to
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Understanding the Kynurenine Pathway: A Narrative Review on its Impact across Chronic Pain Conditions Mol. Pain (IF 2.8) Pub Date : 2024-08-02 Ebrahim Hazrati, Seyed Parsa Eftekhar, Reza Mosaed, Saeed Shiralizadeh Dini, Mehrshad Namazi
Chronic pain is a debilitating symptom with a significant negative impact on the quality of life and socioeconomic status, particularly among adults and the elderly. Major Depressive Disorder (MDD) stands out as one of the most important comorbid disorders accompanying chronic pain. The kynurenine pathway serves as the primary route for tryptophan degradation and holds critical significance in various
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Analyzing Substance Levels and Pain Perception in Painless Labor: The Impact of Spinal Epidural Analgesia Mol. Pain (IF 2.8) Pub Date : 2024-07-31 Fahmi Agnesha, Eti Nurwening Solikhah, Djayanti Sari, Rianza Ainunnisa
Background: Inflammation affects labor by influencing contractions and dilation. Pain, often linked to tissue ischemia, involves mediators like nitric oxide (NO), TNF-α, and substance P (SP). Neuraxial analgesia, including combined spinal epidural analgesia (SEA) with levobupivacaine, is preferred for its effectiveness and minimal side effects in painless labor. Understanding the impact of painless
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Histamine H4 receptor and TRPV1 mediate itch induced by cadaverine, a metabolite of the microbiome Mol. Pain (IF 2.8) Pub Date : 2024-07-31 Shiyu Sun, Xi Yin, Junyi Ma, Xuelong Wang, Xuemei Xu, Jingni Wu, Chengwei Zhang, Ying Lu, Tong Liu, Li Zhang, Peipei Kang, Bin Wu, Guokun Zhou
Cadaverine is an endogenous metabolite produced by the gut microbiome with various activity in physiological and pathological conditions. However, whether cadaverine regulates pain or itch remains unclear. In this study, we first found that cadaverine may bind to histamine 4 receptor (H4R) with higher docking energy score using molecular docking simulations, suggesting cadaverine may act as an endogenous
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Causal Associations of Immune Cell Phenotypes with Migraine: A Mendelian Randomization Study Mol. Pain (IF 2.8) Pub Date : 2024-07-31 Weifang Chai, Weihao Chai, Gei Guo
Background The interaction between the immune system and the brain, crucial for blood-brain barrier integrity, is a potential factor in migraine development. Although there's evidence of a connection between immune dysregulation and migraine, a clear causal link has been lacking. To bridge this knowledge gap, we performed an MR analysis of 731 immune cell phenotypes to determine their causality with
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Optotagging and Characterization of GABAergic Rostral Ventromedial Medulla (RVM) neurons Mol. Pain (IF 2.8) Pub Date : 2024-07-26 Taylor L Follansbee, Henry Le Chang, Mirela Lodi Carstens, Yun Guan, Earl Carstens, Xinzhong Dong
The transmission of nociceptive and pruriceptive signals in the spinal cord is greatly influenced by descending modulation from brain areas such as the rostral ventromedial medulla (RVM). Within the RVM 3 classes of neurons have been discovered which are relevant to spinal pain modulation, the On, Off, and Neutral cells. These neurons were discovered due to their functional response to nociceptive
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Inhibition of calcium-stimulated adenylyl cyclase subtype 1 (AC1) for the treatment of pain and anxiety symptoms in Parkinson’s disease mice model Mol. Pain (IF 2.8) Pub Date : 2024-06-24 Zhaoxiang Zhou, Qi-Yu Chen, Min Zhuo, Pingyi Xu
Pain and anxiety are two common and undertreated non-motor symptoms in Parkinson’s disease (PD), which affect the life quality of PD patients, and the underlying mechanisms remain unclear. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical long-term potentiation (LTP) and injury induced synaptic potentiation in the cortical
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Assessment of orofacial nociceptive behaviors of mice with the sheltering tube method: Oxaliplatin-induced mechanical and cold allodynia in orofacial regions Mol. Pain (IF 2.8) Pub Date : 2024-05-31 Saurav Gupta, Jennifer Ling, Jianguo Gu
Preclinical studies on pathological pain rely on the von Frey test to examine changes in mechanical thresholds and the acetone spray test to determine alterations in cold sensitivity in rodents. These tests are typically conducted on rodent hindpaws, where animals with pathological pain show reliable nocifensive responses to von Frey filaments and acetone drops applied to the hindpaws. Pathological
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Role of ERK in gender difference of fibromyalgia pain Mol. Pain (IF 2.8) Pub Date : 2024-05-31 Ju-Hsin Chang, Ke-Wei Chen, Shih-Ying Tsai, Yen-Jing Zeng, Chi-Yuan Li, Kuen-Bao Chen, Yeong-Ray Wen
This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis
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Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice Mol. Pain (IF 2.8) Pub Date : 2024-05-25 Zi-Long Yi, Jin-Nan Lu, Jin-Jin Zhu, Tian-Tian He, Yi-Ran Xu, Zi-Wei Huang, Yong-Chang Li, Guang-Yin Xu
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the
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Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model Mol. Pain (IF 2.8) Pub Date : 2024-05-22 Ratan K Banik, Twan Sia, Malcolm E Johns, Phu V. Tran, Andrew Y. Cheng, Sudarshan Setty, Donald Simone
Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male
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Reduced Capsaicin-Induced Mechanical Allodynia and Neuronal Responses in the DRG in the Presence of Ptpn6 Overexpression Mol. Pain (IF 2.8) Pub Date : 2024-05-16 Robin Vroman, Shingo Ishihara, Spencer Fullam, Matthew J Wood, Natalie S Adamczyk, Nolan Lomeli, Fransiska Malfait, Anne-Marie Malfait, Rachel E Miller, Adrienn Markovics
Transient Receptor Potential Vanilloid 1 (TRPV1) is a nonselective cation channel expressed by pain-sensing neurons and has been an attractive target for the development of drugs to treat pain. Recently, Src homology region 2 domain-containing phosphatase-1 (SHP-1, encoded by Ptpn6) was shown to dephosphorylate TRPV1 in dorsal root ganglia (DRG) neurons, which was linked with alleviating different
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Recruitment of cortical silent responses by forskolin in the anterior cingulate cortex of adult mice Mol. Pain (IF 2.8) Pub Date : 2024-05-14 Yujie Ma, Jinjin Wan, Qi-Yu Chen, Min Zhuo
Recent studies using different experimental approaches demonstrate that silent synapses may exist in adult cortex including the sensory cortex and anterior cingulate cortex (ACC). Postsynaptic form of long-term potentiation (LTP) in the ACC recruits some of these silent synapses and the activity of calcium-stimulated adenylyl cyclases (ACs) is required for such recruitment. It is unknown if chemical
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Electroacupuncture improves allodynia and central sensitization via modulation of microglial activation associated P2X4R and inflammation in a rat model of migraine Mol. Pain (IF 2.8) Pub Date : 2024-05-14 Min Zhou, Fang Pang, Dongmei Liao, Yunhao Yang, Ying Wang, Zhuxin Yang, Xinlu He, Chenglin Tang
Background:Recent studies have demonstrated that activated microglia were involved in the pathogenesis of central sensitization characterized by cutaneous allodynia in migraine.Activation of microglia is accompanied by increased expression of its receptors and release of inflammatory mediators.Acupuncture and its developed electroacupuncture (EA) have been recommended as an alternative therapy for
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A novel anti-pruritic: Topical co-administration of high molecular weight hyaluronan (HMWH) with protamine, a transdermal transport enhancer Mol. Pain (IF 2.8) Pub Date : 2024-05-10 Paul G Green, Jon D Levine
Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight
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Grape seed-derived procyanidins decreases neuropathic pain and nerve regeneration by suppression of TLR4-Myd88 signaling Mol. Pain (IF 2.8) Pub Date : 2024-05-08 Li Hu, Erdan An, zhipeng Zhu, Ying Cai, Xiaoyan Ye, Hongmei Zhou, Hejia Ge
Background:Recent studies have shown that peripheral nerve regeneration process is closely related to neuropathic pain. Toll-like receptor 4 (TLR4) signaling was involved in different types of pain and nerve regeneration. TLR4 induced the recruitment of myeloid differentiation factor-88 adaptor protein (MyD88) and NF-κB-depended transcriptional process in sensory neurons and glial cells, which produced
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Low-frequency electroacupuncture exerts antinociceptive effects through activation of POMC neural circuit induced endorphinergic input to the periaqueductal gray from the arcuate nucleus Mol. Pain (IF 2.8) Pub Date : 2024-04-27 zhigang lu, Qian Wang, Zhonghao Li, Dengyun Nie, Xinru Mu, Yuxuan Wang, Yongwei Jiang, Yongchen Zhang
It has been widely recognized that electroacupuncture (EA) inducing the release of β-endorphin represents a crucial mechanism of EA analgesia. The ARC is a vital component of the endogenous opioid peptide system. However, the specific mechanisms how EA facilitates the release of β-endorphin within the ARC, eliciting analgesic effects are yet to be elucidated. In this study, we conducted in vivo and
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MOTS-c is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of AMPK/PGC-1α -mediated mitochondrial biogenesis Mol. Pain (IF 2.8) Pub Date : 2024-04-25 Lingfei Xu, Xihui Tang, Long Yang, Min Chang, Yuqing Xu, Qingsong Chen, Chen Lu, Su Liu, Jinhong Jiang
Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. MOTS-c, a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate
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The Regulation of the PD-1/PD-L1 Pathway in Imiquimod-Induced Chronic Psoriasis Itch and Itch Sensitization in Mouse Mol. Pain (IF 2.8) Pub Date : 2024-04-18 Zhehao Xu, Yue Wang, Changcheng Jiang, Zhengwei Wang, Yongfeng Chen, Manli Fan
PD-1/PD-L1 inhibitors have been demonstrated to induce itch in both humans and experimental animals. However, whether the PD-1/PD-L1 pathway is involved in the regulation of chronic psoriatic itch remains unclear. This study aimed to investigate the role of the PD-1/PD-L1 pathway in imiquimod-induced chronic psoriatic itch. The intradermal injection of PD-L1 in the nape of neck significantly alleviated
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Concomitant use of Pre-emptive analgesia with Local and General Anesthesia in Rat Uterine Surgical Pain Model Mol. Pain (IF 2.8) Pub Date : 2024-04-18 Saima Mumtaz, Najma Baseer, Syed Hamid Habib
Preemptive analgesia is used for postoperative pain management, providing pain relief with few adverse effects. In this study, the effect of a preemptive regime on rat behavior and c-fos expression in the spinal cord of the uterine surgical pain model was evaluated. Method: It was a lab-based experimental study in which sixty female Sprague-Dawley rats; eight to ten weeks old, weighing 150–300 gm were
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Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain Mol. Pain (IF 2.8) Pub Date : 2024-04-10 Mingzhu Zhai, Jiabin Huang, Shaomin Yang, Na Li, Jun Zeng, Yi Zheng, Wuping Sun, Benqing Wu
Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain
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Neurotropin® ameliorates chronic pain associated with scar formation in a mouse model: A gene expression analysis of the inflammatory response Mol. Pain (IF 2.8) Pub Date : 2024-03-21 Xuan Zhou, Hiroki Iida, Yugiang Li, Akinobu Ota, Lisheng Zhuo, Reiko Nobuhara, Yuki Terajima, Mitsuru Naiki, A. Hari Reddi, Koji Kimata, Takahiro Ushida
Background: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin® (NTP) is a nonprotein extract from inflamed skin of rabbits inoculated with vaccinia virus and has been widely used for the treatment of chronic pain. However, the in vivo effects of NTP on painful scar formation have not been determined. To investigate
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Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain Mol. Pain (IF 2.8) Pub Date : 2024-03-06 Yu-Xue Zhao, Ming-Jiang Yao, Jian-Wu Shen, Wen-Xi Zhang, Yuan-Xi Zhou
Background: Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture
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Effects of inflammation on the properties of Nav1.8ChR2-positive and Nav1.8ChR2-negative afferent mechanoreceptors in the hindpaw glabrous skin of mice Mol. Pain (IF 2.8) Pub Date : 2024-03-05 Akihiro Yamada, Ayaka Yamada, Jennifer Ling, Hidemasa Furue, Jianguo Gu
We recently used Nav1.8ChR2 mice in which Nav1.8-expressing afferents were optogenetically tagged to classify mechanosensitive afferents into Nav1.8ChR2-postive and Nav1.8ChR2-negative mechanoreceptors. We found that the former were mainly high threshold mechanoreceptors (HTMRs), while the latter were low threshold mechanoreceptors (LTMRs). In the present study, we further investigated whether the
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Nociception related biomolecules in the adult human saliva: a scoping review with additional quantitative focus on cortisol Mol. Pain (IF 2.8) Pub Date : 2024-02-22 Roxaneh Zarnegar, Angeliki Vounta, Qiuyuan Li, Sara Ghoreishizadeh
Nociception related salivary biomolecules can be useful patients who are not able to self-report pain. We present the existing evidence on this topic using the PRISMA-ScR guidelines and a more focused analysis of cortisol change after cold pain induction using the direction of effect analysis combined with risk of bias analysis using ROBINS-I. Five data bases were searched systematically for articles
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A note on estimating absolute cytosolic Ca2+ concentration in sensory neurons using a single wavelength Ca2+ indicator Mol. Pain (IF 2.8) Pub Date : 2024-02-21 James P Higham, Ewan St John Smith, David C Bulmer
Ca2+ imaging is frequently used in the investigation of sensory neuronal function and nociception. In vitro imaging of acutely dissociated sensory neurons using membrane-permeant fluorescent Ca2+ indicators remains the most common approach to study Ca2+ signalling in sensory neurons. Fluo4 is a popular choice of single-wavelength indicator due to its brightness, high affinity for Ca2+ and ease of use
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Acute pulpitis promotes purinergic signaling to induce pain in rats via P38MAPK/NF-κB signaling pathway Mol. Pain (IF 2.8) Pub Date : 2024-02-08 Yangxi Chen, Jun Hu, Fang Qi, Yiqun Kang, Tiejun Zhang, Li Wang
Toothache is one of the most common types of pain, but the mechanisms underlying pulpitis-induced pain remain unknown. The ionotropic purinergic receptor family (P2X) is reported to mediate nociception in the nervous system. This study aims to investigate the involvement of P2X3 in the sensitisation of the trigeminal ganglion (TG) and the inflammation caused by acute pulpitis. An acute tooth inflammation
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Methylglyoxal activates transient receptor potential A1/V1 via reactive oxygen species in the spinal dorsal horn Mol. Pain (IF 2.8) Pub Date : 2024-02-07 Takeru Ueno, Manabu Yamanaka, Wataru Taniguchi, Naoko Nishio, Yuki Matsuyama, Ryo Miyake, Yuta Kaimochi, Terumasa Nakatsuka, Hiroshi Yamada
Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the
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Protectin D1 Ameliorates Non-compressive Lumbar Disc Herniation through SIRT1-mediated CGRP Signaling Mol. Pain (IF 2.8) Pub Date : 2024-01-30 Yuchang Zhu, Yi Zhang, Xiao Gao, Lingxing Li, Yuru Tang, Yi hao Wang
Background: Neuro-inflammatory response promotes the initiation and sustenance of lumbar disc herniation (LDH). Protectin D1 (PD1), as a new type of specialized pro-resolving mediator (SPM), can improve the prognosis of various inflammatory diseases. Recent studies have shown that over representation of calcitonin gene-related peptides (CGRP) may activate nociceptive signaling following nerve injury
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Long-term plasticity of NMDA GluN2B (NR2B) receptor in anterior cingulate cortical synapses Mol. Pain (IF 2.8) Pub Date : 2024-01-22 Min Zhuo
The anterior cingulate cortex (ACC) is a key cortical area for pain perception, emotional fear and anxiety. Cortical excitation is thought to be the major mechanism for chronic pain and its related emotional disorders such as anxiety and depression. GluN2B (or called NR2B) containing NMDA receptors play critical roles for such excitation. Not only does the activation of GluN2B contributes to the induction
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Isolectin B4 (IB4)-conjugated streptavidin for the selective knockdown of proteins in IB4-positive (+) nociceptors Mol. Pain (IF 2.8) Pub Date : 2024-01-22 Oliver Bogen, Dionéia Araldi, Anatol Sucher, Kord Kober, Peter T Ohara, Jon D Levine
In vivo analysis of protein function in nociceptor subpopulations using antisense oligonucleotides and short interfering RNAs is limited by their non-selective cellular uptake. To address the need for selective transfection methods, we covalently linked isolectin B4 (IB4) to streptavidin and analyzed whether it could be used to study protein function in IB4(+)-nociceptors. Rats treated intrathecally
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Sensitization of human and rat nociceptors by low dose morphine is toll-like receptor 4-dependent Mol. Pain (IF 2.8) Pub Date : 2024-01-10 Eugen V Khomula, Dionéia Araldi, Paul G Green, Jon D Levine
While opioids remain amongst the most effective treatments for moderate-to-severe pain, their substantial side effect profile remains a major limitation to broader clinical use. One such side effect is opioid-induced hyperalgesia (OIH), which includes a transition from opioid-induced analgesia to pain enhancement. Evidence in rodents supports the suggestion that OIH may be produced by the action of
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Effects of systemic oxytocin administration on ultraviolet B-induced nociceptive hypersensitivity and tactile hyposensitivity in mice Mol. Pain (IF 2.8) Pub Date : 2024-01-04 M Danilo Boada, Silvia Gutierrez, James C Eisenach
Ultraviolet B (UVB) radiation induces cutaneous inflammation, leading to thermal and mechanical hypersensitivity. Here, we examine the mechanical properties and profile of tactile and nociceptive peripheral afferents functionally disrupted by this injury and the role of oxytocin (OXT) as a modulator of this disruption. We recorded intracellularly from L4 afferents innervating the irradiated area (5
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Projections from infralimbic medial prefrontal cortex glutamatergic outputs to amygdala mediates opioid induced hyperalgesia in male rats Mol. Pain (IF 2.8) Pub Date : 2024-01-04 Ling-Ling Cui, Xi-Xi Wang, Han Liu, Fang Luo, Chen-Hong Li
Repeated use of opioid analgesics may cause a paradoxically exacerbated pain known as opioid-induced hyperalgesia (OIH), which hinders effective clinical intervention for severe pain. Currently, little is known about the neural circuits underlying OIH modulation. Previous studies suggest that laterocapsular division of the central nucleus of amygdala (CeLC) is critically involved in the regulation
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Morphine acts in vitro to directly prime nociceptors. Mol. Pain (IF 2.8) Pub Date : 2024-01-01 Eugen V Khomula,Jon D Levine
Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E2 (PGE2)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE2-induced nociceptor sensitization. In the present
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Mechanical and chemical itch regulated by neuropeptide Y-Y1 signaling. Mol. Pain (IF 2.8) Pub Date : 2024-01-01 Sihan Chen,Junhui Chen,Dan Tang,Wen Yin,Saihong Xu,Po Gao,Yingfu Jiao,Weifeng Yu
Itch is a somatosensory sensation to remove potential harmful stimulation with a scratching desire, which could be divided into mechanical and chemical itch according to diverse stimuli, such as wool fiber and insect biting. It has been reported that neuropeptide Y (NPY) neurons, a population of spinal inhibitory interneurons, could gate the transmission of mechanical itch, with no effect on chemical
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Esketamine inhibits the c-Jun N-terminal kinase pathway in the spinal dorsal horn to relieve bone cancer pain in rats. Mol. Pain (IF 2.8) Pub Date : 2024-01-01 Chenxia Duan,Yi Zhu,Zhuoliang Zhang,Tiantian Wu,Mengwei Shen,Jinfu Xu,Wenxin Gao,Jianhua Pan,Lei Wei,Huibin Su,Chenghuan Shi
Cancer-induced bone pain (CIBP) is one of the most common and feared symptoms in patients with advanced tumors. The X-C motif chemokine ligand 12 (CXCL12) and the CXCR4 receptor have been associated with glial cell activation in bone cancer pain. Moreover, mitogen-activated protein kinases (MAPKs), as downstream CXCL12/CXCR4 signals, and c-Jun, as activator protein AP-1 components, contribute to the
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Newly discovered functions of miRNAs in neuropathic pain: Transitioning from recent discoveries to innovative underlying mechanisms. Mol. Pain (IF 2.8) Pub Date : 2024-01-01 Hasan Golmakani,Amir Azimian,Ebrahim Golmakani
Neuropathic pain is a widespread clinical issue caused by somatosensory nervous system damage, affecting numerous individuals. It poses considerable economic and public health challenges, and managing it can be challenging due to unclear underlying mechanisms. Nevertheless, emerging evidence suggests that neurogenic inflammation and neuroinflammation play a role in developing pain patterns. Emerging
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Kilohertz high-frequency electrical stimulation ameliorate hyperalgesia by modulating transient receptor potential vanilloid-1 and N-methyl-D-aspartate receptor-2B signaling pathways in chronic constriction injury of sciatic nerve mice. Mol. Pain (IF 2.8) Pub Date : 2024-01-01 Kexin Fang,Peixin Lu,Wen Cheng,Bin Yu
The number of patients with neuropathic pain is increasing in recent years, but drug treatments for neuropathic pain have a low success rate and often come with significant side effects. Consequently, the development of innovative therapeutic strategies has become an urgent necessity. Kilohertz High Frequency Electrical Stimulation (KHES) offers pain relief without inducing paresthesia. However, the
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Spinal HDAC6 mediates nociceptive behaviors induced by chronic constriction injury via neuronal activation and neuroinflammation. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Kai Sun,Hao Zhang,Ting Zhang,Nan Sun,Jingru Hao,Zhiping Wang,Can Gao
Neuropathic pain (NP) is often accompanied by psychiatric comorbidities and currently lacks effective treatment. Prior research has shown that HDAC6 plays a crucial role in pain sensitization, but the specific mechanisms remain unclear. HDAC6 inhibitors have been found to alleviate mechanical allodynia caused by inflammation and peripheral nerve damage. In this study, we investigated the cellular mechanisms
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Dehydrocorydaline alleviates sleep deprivation-induced persistent postoperative pain in adolescent mice through inhibiting microglial P2Y12 receptor expression in the spinal cord. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Haikou Yang,Yufeng Zhang,Qingling Duan,Kun Ni,Yang Jiao,Jixiang Zhu,Jian Sun,Wei Zhang,Zhengliang Ma
During adolescence, a second period of central nervous system (CNS) plasticity that follows the fetal period, which involves sleep deprivation (SD), becomes apparent. SD during adolescence may result in abnormal development of neural circuits, causing imbalance in neuronal excitation and inhibition, which not only results in pain, but increases the chances of developing emotion disorders in adulthood
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AMPAkines have site-specific analgesic effects in the cortex. Mol. Pain (IF 2.8) Pub Date : 2024-01-01 Elaine Zhu,Dave Mathew,Hyun Jung Jee,Mengqi Sun,Weizhuo Liu,Qiaosheng Zhang,Jing Wang
Different brain areas have distinct roles in the processing and regulation of pain and thus may form specific pharmacological targets. Prior research has shown that AMPAkines, a class of drugs that increase glutamate signaling, can enhance descending inhibition from the prefrontal cortex (PFC) and nucleus accumbens. On the other hand, activation of neurons in the anterior cingulate cortex (ACC) is
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Saltatory conduction and intrinsic electrophysiological properties at the nodes of ranvier of Aα/β-afferent fibers and Aα-efferent fibers in rat sciatic nerves. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Sotatsu Tonomura,Jianguo G Gu
Large-diameter myelinated fibers in sciatic nerves are composed of both Aα/β-afferent fibers and Aα-efferent fibers to convey sensory and motor impulses, respectively, via saltatory conduction for rapid leg responses. Saltatory conduction and electrophysiological properties at the nodes of Ranvier (NRs) of these sciatic nerve fibers have not been directly studied. We used ex vivo sciatic nerve preparations
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Pain-related behavioral and electrophysiological actions of dynorphin A (1-17). Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Justin E LaVigne,Ian M Adams,Marena A Montera,Karin N Westlund,Sascha Ra Alles
Dynorphin A (1-17) (DynA17) has been identified as a key regulator of both sensory and affective dimensions of chronic pain. Following nerve injury, increases in DynA17 have been reported in the spinal and supraspinal areas involved in chronic pain. Blocking these increases provides therapeutic benefits in preclinical chronic pain models. Although heavily characterized at the behavioral level, how
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Duloxetine prevents bortezomib and paclitaxel large-fiber chemotherapy-induced peripheral neuropathy (LF-CIPN) in sprague dawley rats. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Niloufar Mansooralavi,Eugen V Khomula,Jon D Levine
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting oncology patients' quality of life, chemotherapy-induced large-fiber (LF) neuropathy is amongst the least well understood components of CIPN, and one for which there is currently no established therapy. Preliminary clinical observations
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BDNF-TrkB signaling pathway-mediated microglial activation induces neuronal KCC2 downregulation contributing to dynamic allodynia following spared nerve injury. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Zihan Hu,Xinren Yu,Pei Chen,Keyu Jin,Jing Zhou,Guoxiang Wang,Jiangning Yu,Tong Wu,Yulong Wang,Fuqing Lin,Tingting Zhang,Yun Wang,Xuan Zhao
Mechanical allodynia can be evoked by punctate pressure contact with the skin (punctate mechanical allodynia) and dynamic contact stimulation induced by gentle touching of the skin (dynamic mechanical allodynia). Dynamic allodynia is insensitive to morphine treatment and is transmitted through the spinal dorsal horn by a specific neuronal pathway, which is different from that for punctate allodynia
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Sub-anaesthetic dose of propofol attenuates mechanical allodynia in chronic post-ischaemic pain via regulation of PTEN/PI3K/IL-6 signalling. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Siu Yi Doreen Leung,Fei Meng,Jingjing Liu,Aijia Jessica Liu,Hei Lui Lhotse Ng,Chi Wai Cheung,Stanley Sau Ching Wong
Background: Propofol is an intravenous anaesthetic drug that has been shown to reduce inflammatory pain. Complex regional pain syndrome (CRPS) type I is a pain condition characterized by autonomic, motor and sensory disturbance. The chronic post-ischaemic pain (CPIP) model is a well-established model to recapture CRPS-I syndromes pre-clinically by non-invasive ischaemic-reperfusion (IR) injury. In
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The effects of chronic high-dose morphine on microgliosis and the microglial transcriptome in rat spinal cord. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Fredrik Hg Ahlström,Hanna Viisanen,Leena Karhinen,Kert Mätlik,Kim J Blomqvist,Tuomas O Lilius,Yulia A Sidorova,Vinko Palada,Pekka V Rauhala,Eija A Kalso
Background: Opioids are efficacious and safe analgesic drugs in short-term use for acute pain but chronic use can lead to tolerance and dependence. Opioid-induced microglial activation may contribute to the development of tolerance and this process may differ between males and females. A link is suggested between this microglial activation and inflammation, disturbances of circadian rhythms, and neurotoxic
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Activation of neurons and satellite glial cells in the DRG produces morphine-induced hyperalgesia. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Shunsuke Yamakita,Daisuke Fujita,Kazuki Sudo,Daiki Ishikawa,Kohsuke Kushimoto,Yasuhiko Horii,Fumimasa Amaya
Activation of neurons and glial cells in the dorsal root ganglion is one of the key mechanisms for the development of hyperalgesia. The aim of the present study was to examine the role of neuroglial activity in the development of opioid-induced hyperalgesia. Male rats were treated with morphine daily for 3 days. The resultant phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in the
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Roles of mast cells and their interactions with the trigeminal nerve in migraine headache. Mol. Pain (IF 2.8) Pub Date : 2023-01-01 Leo C Guan,Xinzhong Dong,Dustin P Green
Migraine pain is characterized by an intense, throbbing pain in the head area and possesses complex pathological and physiological origins. Among the various factors believed to contribute to migraine are mast cells (MCs), resident tissue immune cells that are closely associated with pain afferents in the meninges. In this review, we aim to examine and discuss recent findings on the individual roles
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Genetic evidence of the function of Phox2a-expressing anterolateral system neurons in the transmission of chronic pain Mol. Pain (IF 2.8) Pub Date : 2023-04-04 Xinying Zhang, Magali Millecamps, Artur Kania
The development of the chronic neuropathic pain state often originates at the level of peripheral sensory neurons, whose abnormal function elicits central sensitization and maladaptive plasticity i...
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Functional bias of morphine and oliceridine under conditions of minor injury Mol. Pain (IF 2.8) Pub Date : 2023-04-03 Chinwe Nwaneshiudu, Xiao-Yu Shi, Peyman Sahbaie, J David Clark
Recent reports suggest pain from surgical injury may influence the risks associated with exposure to opioids. In mice, hind-paw incision attenuates morphine-primed reinstatement due to kappa opioid...
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Melatonin attenuated chronic visceral pain by reducing Nav1.8 expression and nociceptive neuronal sensitization Mol. Pain (IF 2.8) Pub Date : 2023-03-31 Meng-Dan Lv, Ying-Xue Wei, Jian-Peng Chen, Ming-Yao Cao, Qian-Liang Wang, Shufen Hu
Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, and its specific pathogenesis is still unclear. We have previously reported that TTX-resistant (TTX-R) s...
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Chemokine CCL7 mediates trigeminal neuropathic pain via CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice Mol. Pain (IF 2.8) Pub Date : 2023-03-30 Lin-Peng Zhu, Meng-Lin Xu, Bao-Tong Yuan, Ling-Jie Ma, Yong-Jing Gao
Background: Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to ...