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Molecular Pain

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https://www.readbyqxmd.com/read/29968518/-express-trpa1-sensitization-during-diabetic-vascular-impairment-contributes-to-cold-hypersensitivity-in-a-mouse-model-of-painful-diabetic-peripheral-neuropathy
#1
Haruka Hiyama, Yuichi Yano, Kanako So, Satoshi Imai, Kazuki Nagayasu, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko
BACKGROUND: Diabetic peripheral neuropathy is a common long-term complication of diabetes. Accumulating evidence suggests that vascular impairment plays important roles in the pathogenesis of diabetic peripheral neuropathy, while the mechanism remains unclear. We recently reported that transient receptor potential ankyrin 1 (TRPA1) is sensitized by hypoxia, which can contribute to cold hypersensitivity. In this study, we investigated the involvement of TRPA1 and vascular impairment in painful diabetic peripheral neuropathy using streptozotocin-induced diabetic model mice...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29956587/-express-therapeutic-potential-of-pak1-inhibition-for-pain-associated-with-cutaneous-burn-injury
#2
Yiqun Guo, Curtis Benson, Myriam Hill, Stefanie Henry, Philip Effraim, Stephen Waxman, Sulayman Dib-Hajj, Andrew Michael Tan
Painful burn injuries are among the most debilitating form of trauma, globally ranking in the top 15 leading causes of chronic disease burden. Despite its prevalence, however, chronic pain after burn injury is under-studied. We previously demonstrated the contribution of the Rac1-signaling pathway in several models of neuropathic pain, including burn injury. However, Rac1 belongs to a class of GTPases with low therapeutic utility due to their complex intracellular dynamics. To further understand the mechanistic underpinnings of burn-induced neuropathic pain, we performed a longitudinal study to address the hypothesis that inhibition of the downstream effector of Rac1, Pak1, will improve pain outcome following a second-degree burn injury...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29956586/non-muscle-myosin-ii-isoforms-interact-with-sodium-channel-alpha-subunits
#3
Bhagirathi Dash, Chongyang Han, Stephen Waxman, Sulayman Dib-Hajj
Sodium channels play pivotal roles in health and diseases due to their ability to control cellular excitability. The pore-forming α-subunit (Naα) of the voltage-sensitive channels (i.e., Nav1.1-1.9) and the non-voltage-dependent channel (i.e., Nax) share a common structural motif and selectivity for sodium ions. We hypothesized that the actin based non-muscle myosin II motor proteins (NM-IIs), non-muscle myosin heavy chain (NMHC)-IIA/myh9 and NMHC-IIB/myh10, might interact with Naα subunits to play an important role in their transport, trafficking and/or function...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29956585/-express-nuclear-factor-kappa-b-regulated-monocyte-chemoattractant-protein-1-chemokine-cc-motif-receptor-2-expressing-in-spinal-cord-contributes-to-the-maintenance-of-cancer-induced-bone-pain-in-rats
#4
Yungong Wang, Huadong Ni, Hongbo Li, Houshen Deng, Long Sheng Xu, Shijie Xu, Ying Zheng, Hui Shen, Huan Pan, Ming Yao
BACKGROUND: Chemokine, monocyte chemoattractant protein-1 (MCP-1), is a potential factor to cause cancer-induced bone pain (CIBP). NF-kB signaling is very important in mediating the expression of chemokines and may have a role in CIBP. However, the mechanism is still unclear. The present study investigates the role of NF-kB in CIBP by regulating MCP-1/chemokine CC motif receptor 2 (CCR2) signaling pathway. METHODS: A rat CIBP model was established by injecting Walker 256 cells into the femur medullary cavity...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29956582/-express-chronic-inflammatory-pain-induced-gabaergic-synaptic-plasticity-in-the-adult-mouse-anterior-cingulate-cortex
#5
Kohei Koga, Shuji Shimoyama, Akihiro Yamada, Tomonori Furukawa, Yoshikazu Nikaido, Hidemasa Furue, Kazuhiko Nakamura, Shinya Ueno
No abstract text is available yet for this article.
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29923456/transcription-independent-expression-of-pkm%C3%AE-in-the-anterior-cingulate-cortex-contributes-to-chronically-maintained-neuropathic-pain
#6
Hyoung-Gon Ko, Sanghyun Ye, Dae-Hee Han, Pojeong Park, Chae-Seok Lim, Kyungmin Lee, Min Zhuo, Bong-Kiun Kaang
Protein kinase M ζ is well known for its role in maintaining memory and pain. Previously, we revealed that the activation of protein kinase M ζ in the anterior cingulate cortex plays a role in sustaining neuropathic pain. However, the mechanism by which protein kinase M ζ is expressed in the anterior cingulate cortex by peripheral nerve injury, and whether blocking of protein kinase M ζ using its inhibitor, zeta inhibitory peptide, produces analgesic effects in neuropathic pain maintained chronically after injury, have not previously been resolved...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29921170/-express-atf2-but-not-atf3-participates-in-the-maintenance-of-nerve-injury-induced-tactile-allodynia-and-thermal-hyperalgesia
#7
Ana Belen Salinas-Abarca, Isabel Velazquez-Lagunas, Urzula Franco-Enzastiga, Jorge Elias Torres-López, Hector Isaac Rocha-Gonzalez, Vinicio Granados-Soto
Transcription factors are proteins that modulate the transcriptional rate of target genes in the nucleus in response to extracellular or cytoplasmic signals. Activating transcription factors 2 (ATF2) and 3 (ATF3) respond to environmental signals and maintain cellular homeostasis. There is evidence that inflammation and nerve injury modulate ATF2 and ATF3 expression. However, the function of these transcription factors in pain is unknown. The purpose of this study was to investigate the contribution of ATF2 and ATF3 to nerve injury-induced neuropathic pain...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29921169/-express-auricular-vagus-nerve-stimulation-enhances-central-serotonergic-function-and-inhibits-diabetic-neuropathy-development-in-zucker-fatty-rats
#8
Shayuan Li, Chunli Sun, Peijing Rong, Xu Zhai, Jinling Zhang, Max Baker, Shuxing Wang
Painful neuropathy is a frequent comorbidity in diabetes. Zucker diabetic fatty (ZDF, fa/fa) rats develop type 2 diabetes spontaneously with ageing and show nociceptive hypersensitivity by age of 13wk. In preclinical and clinical studies, the treatment of diabetic neuropathy is challenging but complementary medicine like transcutaneous auricular vagus nerve stimulation (taVNS) appears beneficial to the relief of neuropathic pain. However, the mechanism behind the effectiveness of taVNS remains unclear. In this study we show that daily 30min taVNS (2/15Hz, 2mA) for consecutive 27 days effectively inhibited the development of nociceptive hypersensitivity in ZDF rats as detected by thermal hyperalgesia and mechanical allodynia in hindpaw...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29921161/-express-the-role-of-insula-cerebellum-connection-underlying-aversive-regulation-with-acupuncture
#9
Lijun Bai, Xuan Niu, Zhenyu Liu, Zhen Chen, Xiaocui Wang, Chuanzhu Sun, Zhuonan Wang, Shan Wang, Jieli Cao, Shuoqiu Gan, Geng Fan, Wenmin Huang, Hui Xu, Shangjie Chen, Jie Tian, Lixing Lao, Ming Zhang
Acupuncture at PC6 shows a consistently positive efficacy in nausea response suggested by consensus expert guidelines. Nausea encompasses aversive symptom, as well as strong emotional components. Disgust is a subjective emotion of uneasy commonly accompanying with a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Understanding the brain circuitry by which acupuncture influences the disgust emotion may further elucidate the modulation effect of acupuncture on aversive experience...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29902945/-express-acute-and-chronic-pain-affects-local-field-potential-of-the-medial-prefrontal-cortex-in-different-band-neural-oscillations
#10
Bo Fu, Shao-Nan Wen, Kun Wang, Shao-Jun Liu, Ji-Yan Zhang, Bin Wang
The medial prefrontal cortex (mPFC) is involved in the process of sensory discrimination. In this study, we examined the local field potential (LFP) activity response to the different stages of pain in the Prl, which is a sub-region of the mPFC. Recent studies revealed extensive information about neural oscillations, but there is limited information on the LFP profiles for acute or chronic pain, particularly in freely moving animals. This study showed that acute mechanical pain increases alpha oscillation, and decreases beta and gamma oscillations before spared nerve injury (SNI) surgery...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29900804/-express-participation-of-pro-inflammatory-cytokines-in-neuropathic-pain-evoked-by-chemotherapeutic-oxaliplatin-via-central-gabaergic-pathway
#11
Dongsheng Xu, Hui Zhao, Han Gao, Huling Zhao, Dandan Liu, Jing Li
BACKGROUND: Neuropathic pain is observed in patients as chemotherapeutic oxaliplatin (OXL) is used to treat metastatic digestive tumors; however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of pathophysiology of neuropathic pain. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines (PICs) system of the PAG in regulating mechanical hyperalgesia and cold hypersensitivity evoked by OXL...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29882480/dehydrocorydaline-attenuates-bone-cancer-pain-by-shifting-microglial-m1-m2-polarization-toward-the-m2-phenotype
#12
Wenwen Huo, Ying Zhang, Yue Liu, Yishan Lei, Rao Sun, Wei Zhang, Yulin Huang, Yanting Mao, Chenchen Wang, Zhengliang Ma, Xiaoping Gu
Bone cancer pain remains a major challenge in patients with primary or metastatic bone cancer due to a lack of understanding the mechanisms. Previous studies have revealed the two distinct functional polarization states of microglia (classically activated M1 and alternatively activated M2) in the spinal cord in nerve injury-induced neuropathic pain. However, whether microglia in the spinal cord polarize to M1 and M2 phenotypes and contribute to the development of bone cancer pain remains unclear. In this study, we used a mouse model with bone cancer to characterize the M1/M2 polarization of microglia in the spinal cord during the development of bone cancer pain, and investigated the antinociceptive effects of dehydrocorydaline, an alkaloidal component isolated from Rhizoma corydalis on bone cancer pain...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29877133/morphometric-changes-over-the-whole-brain-in-caffeine-containing-combination-analgesic-overuse-headache
#13
Xiaoyan Chen, Zhiye Chen, Zhao Dong, Mengqi Liu, Shengyuan Yu
Objective To investigate brain morphometric changes in medication-overuse headache with excessive intake of caffeine-containing combination analgesics. Materials and methods We recruited 32 medication-overuse headache patients overusing caffeine-containing combination analgesics and 26 normal controls with matched sex and age. Magnetic resonance T1-weighted images were processed by automatic volume algorithm of brain regions over the whole brain according to the neuromorphometrics template. We explored the volume differences between groups and correlation with clinical variables...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29871537/plastic-change-of-prefrontal-cortex-mediates-anxiety-like-behaviors-associated-with-chronic-pain-in-neuropathic-rats
#14
Kangning Sang, Chaofei Bao, Yushi Xin, Shunan Hu, Xian Gao, Yongsheng Wang, Mark Bodner, Yong-Di Zhou, Xiao-Wei Dong
Clinical studies show that anxiety and chronic pain are concomitant. The neural basis for the comorbidity is unclear. The prefrontal cortex (PFC) has been recognized as a critical area for affective disorders and chronic pain modulation. In this study, we examined the role of the PFC in the pathogenesis of anxiety associated with chronic pain in a rat model of neuropathic pain with spare nerve injury (SNI). The SNI rats showed apparent anxiety-like behaviors in both open field (OF) test and elevated-plus maze (EPM) test eight weeks after surgery...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29806529/hcn2-contributes-to-oxaliplatin-induced-neuropathic-pain-through-activation-of-the-camkii-creb-cascade-in-spinal-neurons
#15
Xiaoyu Liu, Lidong Zhang, Li Jin, Yuanhui Tan, Weiyan Li, Jun Tang
Emerging evidence showed that hyperpolarization-activated cation channels (HCN) participate in the development of inflammatory and neuropathic pain. However, the role of HCN2 in oxaliplatin-induced neuropathic pain remains unknown. Here, we found that HCN2 expression was upregulated in a rat model of oxaliplatin-induced neuropathic pain. Intrathecal injection of ZD7288, an HCN specific inhibitor, decreased the HCN2 level, as well as weakened the neuropathic pain behaviors compared to naive rats. Besides, mechanistic studies revealed that the expression of the spinal N-methyl-D-aspartate receptor subunit 2B was increased after oxaliplatin administration and was reduced by ZD7288 administration...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29790813/increased-na-v-1-7-expression-in-the-dorsal-root-ganglion-contributes-to-pain-hypersensitivity-after-plantar-incision-in-rats
#16
Jiaoli Sun, Ningbo Li, Guangyou Duan, Yi Liu, Shanna Guo, Cong Wang, Changmao Zhu, Xianwei Zhang
Postoperative pain remains a complex problem that is difficult to manage in the clinical context, seriously affecting rehabilitation and the quality of life of patients after surgery. Nociceptors, of which the cell bodies are located in the dorsal root ganglion, are crucial for initiating and conducting the pain signal. The peripheral voltage-gated sodium channels, including Nav 1.7, which is mainly expressed in the dorsal root ganglion, are key to understanding the mechanism underlying postoperative pain. Nav 1...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29790812/nav1-7-is-phosphorylated-by-fyn-tyrosine-kinase-which-modulates-channel-expression-and-gating-in-a-cell-type-dependent-manner
#17
Yangyang Li, Tengteng Zhu, Huan Yang, Sulayman D Dib-Hajj, Stephen G Waxman, Ye Yu, Tian-Le Xu, Xiaoyang Cheng
Voltage-gated sodium channel Nav1.7 is a key molecule in nociception, and its dysfunction has been associated with various pain disorders. Here, we investigated the regulation of Nav1.7 biophysical properties by Fyn, an Src family tyrosine kinase. Nav1.7 was coexpressed with either constitutively active (FynCA ) or dominant negative (FynDN ) variants of Fyn kinase. FynCA elevated protein expression and tyrosine phosphorylation of Nav1.7 channels. Site-directed mutagenesis analysis identified two tyrosine residues (Y1470 and Y1471) located within the Nav1...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29783906/bulleyaconitine-a-attenuates-hyperexcitability-of-dorsal-root-ganglion-neurons-induced-by-spared-nerve-injury-the-role-of-preferably-blocking-nav1-7-and-nav1-3-channels
#18
Man-Xiu Xie, Jie Yang, Rui-Ping Pang, Wei-An Zeng, Han-Dong Ouyang, Yan-Qing Liu, Xian-Guo Liu
Background Oral administration of Bulleyaconitine A, an extracted diterpenoid alkaloid from Aconitum bulleyanum plants, is effective for treating chronic pain in rats and in human patients, but the underlying mechanisms are poorly understood. Results As the hyperexcitability of dorsal root ganglion neurons resulting from the upregulation of voltage-gated sodium (Nav) channels has been proved critical for development of chronic pain, we tested the effects of Bulleyaconitine A on Nav channels in rat spared nerve injury model of neuropathic pain...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29770746/chronic-inflammatory-pain-decreases-the-glutamate-vesicles-in-presynaptic-terminals-of-the-nucleus-accumbens
#19
Chuchu Qi, Baolin Guo, Keke Ren, Han Yao, Mengmeng Wang, Tangna Sun, Guohong Cai, Haiying Liu, Rui Li, Ceng Luo, Wenting Wang, Shengxi Wu
Reward system has been proved to be important to nociceptive behavior, and the nucleus accumbens (NAc) is a key node in reward circuitry. It has been further revealed that dopamine system modulates the NAc to influence the pain sensation, whereas the role of glutamatergic projection in the NAc in the modulation of chronic pain is still elusive. In this study, we used a complete Freund's adjuvant-induced chronic inflammatory pain model to explore the changes of the glutamatergic terminals in the NAc, and we found that following the chronic inflammation, the protein level of vesicular glutamate transporter1 (VGLUT1) was significantly decreased in the NAc...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29770739/novel-ntrk1-mutations-in-chinese-patients-with-congenital-insensitivity-to-pain-with-anhidrosis
#20
Xingzhu Geng, Yanshan Liu, XiuZhi Ren, Yun Guan, Yanzhou Wang, Bin Mao, Xiuli Zhao, Xue Zhang
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder, characterized by loss of algesthesis and inability to sweat. CIPA is known to be caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene ( NTRK1). However, the details of NTRK1 mutations in Chinese CIPA patients remain unclear. In the present study, we recruited 36 CIPA patients from 34 unrelated families in mainland China. Blood samples from these patients and their available familial members were collected and subjected to genetic analysis...
January 2018: Molecular Pain
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