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K Raafat, M Wurglics, M Schubert-Zsilavecz
Prunella vulgaris L. (Lamiaceae) (PV) is a herbaceous plant traditionally utilized in management of diabetes and it has immunomodulatory activity. In this study, acute and subchronic antidiabetic, in-vivo antioxidant and antinociceptive effects of PV were evaluated in alloxan-induced type 1 diabetes (T1D) in a mouse model. Bio-guided fractionation, isolation, RP-HPLC, and (1)H and (13)C NMR identification of the active components responsible for PV effects were determined. RP-HPLC analysis showed that PV contained rosmarinic acid (RA) 4...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Tomohiro Yamashita, Shota Yamamoto, Jiaming Zhang, Miho Kometani, Daisuke Tomiyama, Keita Kohno, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R...
2016: PloS One
W Xia, C D Mørch, D Matre, O K Andersen
BACKGROUND: This study aimed to explore conditioned pain modulation (CPM) effect on long-term potentiation (LTP)-like pain amplification induced by cutaneous 10-Hz conditioning electrical stimulation (CES). METHODS: Conditioned pain modulation was induced by cold pressor conditioning stimulus (CPCS) (4 °C) which was applied immediately before CES in the active session. In the control session, water with a temperature of 32 °C was used. Twenty subjects participated in two sessions in a randomized crossover design with at least 1-week interval...
October 20, 2016: European Journal of Pain: EJP
Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Teng-Fei Li, Nian Gong, Yong-Xiang Wang
Aconitines, including bulleyaconitine A, probably the most bioactive and abundant alkaloids in Aconitum plant, are a group of diester C19-diterpenoid alkaloids with one acetylester group attached to C8 of the diterpenoid skeleton and one benzoylester group to C14. Hydrolysis of both groups is involved in the processing of Aconitum, a traditional Chinese medicinal approach. We recently demonstrated that bulleyaconitine A produced anti-hypersensitivity, which was mediated by stimulation of spinal microglial dynorphin A expression...
2016: Frontiers in Pharmacology
Nabanita Das, Varun Dewan, Peter M Grace, Robin J Gunn, Ryo Tamura, Netanel Tzarum, Linda R Watkins, Ian A Wilson, Hang Yin
Infectious and sterile inflammatory diseases are correlated with increased levels of high mobility group box 1 (HMGB1) in tissues and serum. Extracellular HMGB1 is known to activate Toll-like receptors (TLRs) 2 and 4 and RAGE (receptor for advanced glycation endproducts) in inflammatory conditions. Here, we find that TLR5 is also an HMGB1 receptor that was previously overlooked due to lack of functional expression in the cell lines usually used for studying TLR signaling. HMGB1 binding to TLR5 initiates the activation of NF-κB signaling pathway in a MyD88-dependent manner, resulting in proinflammatory cytokine production and pain enhancement in vivo...
October 18, 2016: Cell Reports
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Rupinder Kaur Sodhi, Anurag Kuhad
TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain...
October 18, 2016: Inflammopharmacology
Nikele Nadur-Andrade, Camila Squarzoni Dale, Victoria Regina da Silva Oliveira, Elaine Flamia Toniolo, Regiane Dos Santos Feliciano, José Antonio da Silva, Stella Regina Zamuner
BACKGROUND: Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv), as well as the mechanisms involved was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Bmv (1 μg) was injected through the intraplantar route in the right hind paw of mice...
October 2016: PLoS Neglected Tropical Diseases
M Andriamamonjy, J-B Delmotte, F Savinelli, H Beaussier, F Coudore
INTRODUCTION: Oxaliplatin is a platinum derivate widely used in cancer treatment but producing dose-limiting peripheral neurotoxicity. Acute neuropathy is characterized by a transient cold-induced distal allodynia whereas chronic neuropathy leads to sensory loss. In order to design a method for quantitative assessment of oxaliplatin-induced peripheral neuropathy, we developed a study that aims to characterize the most appropriate skin area of the hand to perform sensory tests. METHODS: We included patients treated during at least 6 months with oxaliplatin...
October 1, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Cheng-Hua Zhou, Ming-Xing Zhang, Sha-Sha Zhou, Huan Li, Jian Gao, Lei Du, Xiao-Xing Yin
Accumulating evidence has demonstrated that epigenetic modification-mediated changes in pain-related gene expressions play an important role in the development and maintenance of neuropathic pain. Sirtuin 1 (SIRT1), anicotinamide adenosine dinucleotide (NAD)-dependent deacetylase, is involved in the development of chronic pain. Moreover, SIRT1 may be a novel therapeutic target for the prevention of type 2 diabetes mellitus (T2DM). But the role of SIRT1 in T2DM-induced neuropathic pain remains unknown. In this study, we found that spinal SIRT1 expression and activity were down-regulated significantly in high-fat-fed/low-dose STZ-induced neuropathic pain rats...
September 29, 2016: Pain
Ajit Kumar, Sanjeev K Bhoi, Jayantee Kalita, Usha K Misra
OBJECTIVE: In view of the paucity of studies on central poststroke pain (CPSP), in this hospital-based prospective study, we evaluated the frequency, the spectrum, imaging, and quantitative sensory testing in a cohort of stroke patients with CPSP. METHODS: Stroke patients who developed CPSP at onset or during follow-up were included. Patients were subjected to clinical evaluation and sensory testing. The severity of stroke was defined by the Modified Rankin Scale and disability by the Barthel Index...
November 2016: Clinical Journal of Pain
Ram Kandasamy, Jonas J Calsbeek, Michael M Morgan
Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior...
October 13, 2016: Behavioural Brain Research
Lijuan Lu, Cailong Pan, Lu Chen, Liang Hu, Chaoyu Wang, Yuan Han, Zhixiang Cheng, Yanjing Yang, Wen-Tao Liu
Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ (PKCγ), N-methyl-D-aspartate receptor (NMDAR), and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve...
October 15, 2016: Journal of Molecular Cell Biology
Wei Sun, Fei Yang, Yan Wang, Han Fu, Yan Yang, Chun-Li Li, Xiao-Liang Wang, Qing Lin, Jun Chen
Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated...
October 12, 2016: Neuropharmacology
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
Zhenpeng Song, Bingrui Xiong, Hua Zheng, Anne Manyande, Xuehai Guan, Fei Cao, Lifang Ren, Yaqun Zhou, Dawei Ye, Yuke Tian
Major histocompatibility class II (MHC II)-specific activation of CD4(+) T helper cells generates specific and persistent adaptive immunity against tumors. Emerging evidence demonstrates that MHC II is also involved in basic pain perception; however, little is known regarding its role in the development of cancer-induced bone pain (CIBP). In this study, we demonstrate that MHC II expression was markedly induced on the spinal microglia of CIBP rats in response to STAT1 phosphorylation. Mechanical allodynia was ameliorated by either pharmacological or genetic inhibition of MHC II upregulation, which was also attenuated by the inhibition of pSTAT1 and pERK but was deteriorated by intrathecal injection of IFNγ...
October 11, 2016: Brain, Behavior, and Immunity
Brian A Simpson, Ravindra Nannapaneni
BACKGROUND: With its relative simplicity and safety, peripheral nerve field stimulation (PNFS; PENS) is contributing to the re-emergence of peripheral nerve stimulation as an effective therapy for neuropathic pain (NPP). CASE PRESENTATION: A 70-year-old woman had developed severe, medically refractory NPP unilaterally in the scalp and face 20 years earlier, following a maxillofacial surgical procedure. PNFS gave substantial relief of the pain and allodynia and was repeated successfully on a further 25 occasions over the subsequent five years...
October 14, 2016: Neuromodulation: Journal of the International Neuromodulation Society
W Ma, B St-Jacques, U Rudakou, Y N Kim
BACKGROUND: Persistent peripheral sensitization contributes to chronic pain. Plasticity of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) induced by pro-inflammatory mediators contributes to sensitization. Prostaglandin E2 (PGE2) enriched in injured tissues is known not only directly to sensitize DRG neurons, but also to potentiate sensitizing effects of other pain mediators such as capsaicin and its receptor transient receptor potential vanilloid-1 (TRPV1). It remains unknown whether PGE2 potentiates TRPV1 activity by stimulating its synthesis, cell surface and axonal trafficking in DRG neurons...
October 14, 2016: European Journal of Pain: EJP
Satoru Koyanagi, Naoki Kusunose, Marie Taniguchi, Takahiro Akamine, Yuki Kanado, Yui Ozono, Takahiro Masuda, Yuta Kohro, Naoya Matsunaga, Makoto Tsuda, Michael W Salter, Kazuhide Inoue, Shigehiro Ohdo
Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn...
October 14, 2016: Nature Communications
Suzie Noten, Filip Struyf, Enrique Lluch, Marika D'Hoore, Eveline Van Looveren, Mira Meeus
BACKGROUND: Shoulder pain is a common health problem in which changes in shoulder structure cannot always explain the patient's perceived pain. Central sensitization (CS) might play a role in a subgroup of these patients. METHODS: The literature was systematically reviewed to address the role of CS in patients with shoulder pain. Electronic databases PubMed and Web of Knowledge were searched for relevant studies. RESULTS: Eighteen full-text articles were included, methodological quality was scored, and information was extracted...
October 14, 2016: Pain Practice: the Official Journal of World Institute of Pain
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