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Investigating the inhibition of NMDA glutamate receptors in the basolateral nucleus of the amygdala on the pain and inflammation induced by formalin in male Wistar rats

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Frontiers in Biology 2018年第2期13卷 149-155页

作者： Nima Heidary Hedayat Sahraei Mohammad Reza Afarinesh Zahra Bahari Gholam Hossein Meftahi Department of Physiology School of Medicine Zanjan University of Medical Sciences Zanjan Iran Neuroscience Research Center Baqiyatallah University of Medical Sciences Tehran Iran Kerman Cognitive Research Center and Neuroscience Research Center Institute of Neuropharmachology Kerman University of MedicalSciences Kerman Iran Department of Physiology and Biophysics Faculty of Medicine Baqiyatallah University of Medical Sciences Tehran Iran

BACKGROUND： The role of the amygdala in controlling emotional pain has been emphasized in several studies. In this study, the role of the NMDA glutamate receptors in the basolateral nucleus of the amygdala （BLA） in regulating inflammation and emotional pain, induced by formalin, was studied in male rats. METHODS： Male Wistar rats, weighing 250±0 g, were injected with 20 μL of 2% formalin into the paw of the right hind limb. Memantine, at doses of 1 and 5 μg/rat, was injected bilaterally into the BLA five minutes prior to injecting formalin. Following the injection, the pain and inflammation of the paws were measured using Dubbison-Dennis and mercury immersion methods, respectively. The behavior of the animals, including licking time and foot volume, was assessed. RESULTS： The results showed that the inactivation of the NMDA receptors in the BLA in the acute phase of pain reduced the licking time （the emotional aspect of pain）. However, at a high dose （5μg/rat）, memantine exacerbates the pain induced by formalin in the chronic phase. Additionally, the inhibition of the NMDA receptors in the BLA by memantine enhanced the formalin-induced increase in foot volume （inflammation） in a dose-dependent manner. CONCLUSION： The study showed that the NMDA glutamate receptors in the BLA are crucial for the emotional pain and inflammation in both chronic and acute phases of formalin-induced pain. However, their roles are more pronounced in the chronic phase than in the acute phase of pain.

关键词： basolateral nucleus of amygdala formalin test inflammation licking time memantine

Effects of multiple intrathecal administration of L-arginine with different doses on formalin-induced nociceptive behavioral responses in rats

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Neuroscience Bulletin 2010年第3期26卷 211-218页

作者：李宽祁文秀山西医科大学太原030001 山西医科大学汾阳学院生理学教研室汾阳032200

Objective To investigate the effects of nitric oxide （NO） with different doses on modulation of inflammatory pain, and its possible *** NO precursor L-arginine （L-Arg） was intrathecally administered in rats at a dose of 10 μg per day （low dose group） or 250μg per day （high dose group） for a succession of 4 *** saline was applied as a *** the rats were subcutaneously injected with formalin （100μL,2%） into the right hindpaw,and the nociceptive behavioral responses within 1 h were *** 4 h after formalin injection,neuronal NO synthase （nNOS） and c-Fos expression in spinal dorsal horn was examined with immunocytochemistry *** The subcutaneous injection of formalin evoked biphasic behaviors of licking or biting the injected *** was no difference in acute phase of formalin test among the 3 groups,while in tonic phase,the licking and biting time,and the protein levels of nNOS and c-Fos in spinal dorsal horn were significantly decreased in low dose group and increased in high dose group,compared with those in control *** These results suggest that multiple administration of NO with different doses may produce different *** one hand,the low dose of NO can induce *** the other hand,the high dose of NO can induce pronociception.

关键词： L-arginine nitric oxide formalin test pain nitric oxide synthase genes c-fos spinal cord

Up-regulation and time course of protein kinase C immunoreactivity during persistent inflammation of the rat spinal cord

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Neural Regeneration Research 2008年第4期3卷 349-353页

作者： Liping Yang Qingjun Li Department of Neurology the 263 Hospital of Chinese PLA Beijing 101149China Department of Pathophysiology Institute of Basic Medical Science Hebei Medical University Shijiazhuang 050017 Hebei Province China

BACKGROUND： It has been reported that activation and/or translocation of protein kinase C （PKC） is related to hyperalgesia, and changes in PKC expression in the dorsal horn of spinal cord take place during inflammatory pain. OBJECTIVE： To observe PKC changes in the dorsal horn of spinal cord using immunohistochemistry and to measure the time-course during persistent pain produced by chemical stimulation with a right hind-paw injection of formalin. DESIGN： Randomized controlled animal experiment. SETTING： Institute of Basic Medical Science, Hebei Medical University MATERIALS： The present experiment was performed at the Department of Pathophysiology, Institute of Basic Medical Science, Hebei Medical University between September 2000 and June 2002. Forty-two Sprague-Dawley rats, weighing 260-280 g, irrespective of gender, were provided by the Center of Animal Experimentation at Hebei Medical University. PKC antibody was provided by Sigma, USA. Immunohistochemistry kits were purchased from Zhongshan Biotechnology Company, Beijing. HPIAS-1000 definition multicolor system was provided by Qianping Wuxiang Project Company of Tongji Medical University. Animal use during experimentation was consistent with the standards of Animal Ethics Committee. METHODS： Sprague-Dawley rats were divided randomly into control （n = 6） and experimental groups （n = 36）. Experimental rats were given an intracutaneous injection of 5% formalin into the planta surface of the right hind-paw. Animals with inflammatory pain were anesthetized and sacrificed to obtain the L5 spinal region at 1, 3, 12 hours, 1, 3, and 7 days after formalin treatment, with 6 rats in each time group. The spinal cords at the L5 region were collected from the control group following sodium chloride injections into the planta surface of the right hind-paw, identical to the experimental group. MAIN OUTCOME MEASURES： Pain reaction of experimental rats after formalin treatment. PKC-positive neurons, and distribution of PKC-immun

关键词： pain protein kinase C dorsal horn of spinal cord immunohistochemistry formalin test

Comparison of the Analgesic Activity of Antiparkinsonian Aminoadamantane Derivatives Amantadine and Hemantane

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Advances in Parkinson's Disease 2016年第3期5卷 50-60页

作者： Elena Ivanova Inga Kapitsa Elena Valdman Tatyana Voronina Laboratory of Psychopharmacology Zakusov Institute of Pharmacology Moscow Russia

The efficacy of some aminoadamantane derivatives used as neurodegeneration treatments is due to their ability to block NMDA receptors. But this mechanism of pharmacological action can also produce analgesic activity. Analgesic properties of two aminoadamantanes, amantadine (20 mg/kg) and hemantane (20 mg/kg), which were uncompetitive NMDA receptor antagonists, were assessed in rodent models of pain induced by different pain stimuli (tail-flick test, acetic twitches test in mice and formalin test in rats). Additionally, the anti-inflammatory properties of hemantane and amantadine were evaluated in mice with acetic peritonitis and in rats with hind paw edema induced by formalin injection. The results of our study demonstrate that the analgesic activity of the 1-aminoadamantane amantadine differs from the 2-aminoadamantane hemantane. The analgesic activity of amantadine administered intraperitoneally was more pronounced in the case of acute thermal pain in mice compared to hemantane, and only amantadine had a significant analgesic effect on the acute early phase of formalin pain in rats induced by the effect of the algogen on the primary sensory afferents. Hemantane was more effective than amantadine for relieving pain produced by inflammation owing to its pronounced anti-inflammatory activity: only hemantane decreased the amount of acetic twitches in mice that received drugs orally and was effective in the tonic phase of formalin pain in rats.

关键词： NMDA Receptor Antagonists Tail-Flick test Acetic Twitches formalin test Exudative Inflammation

An investigation of the antinociceptive effects of Riluzole in hyperal gesia models of mice

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Journal of Nanjing Medical University 2006年第3期20卷 172-175页

作者： Xiaoping Xia Zhenliang Ma Yinming Zeng Nanjing University Medical School affiliated Drum Tower Hospital Nanjing 210008 China Jiangsu Institute of Anesthesiology Jiangsu Key Laboratory of AnesthesiologyXuzhou Medical College Xuzhou 221002 China

Objective： To investigate the antinociceptive effects of Riluzole administered intraperitoneally in three hyperalgesia model of mice. Methods： Antinociceptive tests in C57BL mice were investigated with formalin test,acetic acid induced writhing test and tail-immersion test. The effects of intraperitoneally Riluzole 2 mg/kg ,4 mg/kg and 8 mg/kg on the pain threshold were observed. Result： We found that i.p. treatment with Riluzole （4 mg/kg and 8 mg/kg） blocked the second phase flinching behavior compared with vehicle （P 〈 0.05）, but not during the first phase in the formalin test. In addition to the formalin test, Riluzole at different dose （from 2 to 8 mg/kg） attenuated acetic acid induced writhing response when compared to vehicle group （P 〈 0.05）. In the tail-immersion test, Riluzole at the highest dose （8 mg/kg） caused significant increase in tail flick response latency as compared to vehicle animals or compared with Baseline （P 〈 0.05）. Conclusion： Our results suggest that glutamate release inhibitor Riluzole can attenuate nociceptive behavior and has differrent antinociceptive characteristic according to the various pain models.

关键词： Riluzole formalin test Inflammation Pain Glutamate nociception

Sex differentiation of effect of microinjection of somatostatin into ventrolateral orbital cortex on formalin-induced nociceptive behavior in rats

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Sex differentiation of effect of microinjection of somatosta...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Chao-Ling QU~(1,*),Bo XING~2,Yong-Hui DANG~2,Yan ZHAO~2,Feng-Yi XU~1,Fu-Quan HUO~1,Jing-Shi TANG~1 1 Department of Physiology and Pathophysiology,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education,Xi’an Jiaotong University School of Medicine,Xi’an 710061,China 2 Department of Forensic Medicine,Key Laboratory of Environment and Gene Related to Diseases,Ministry of Education, Xi’an Jiaotong University School of Medicine,Xi’an 710061,China

Objective As a neuromodulator,somatostatin(SOM) and its receptors are involved in the antinociception in the spinal cord and the supraspinal ***,sex differences are observed in some pain-related *** studies have indicated that the ventrolateral orbital cortex(VLO) is involved in modulation of nociception as part of an endogenous analgesic system consisting of the spinal cord-nucleus submedius-VLO-periaqueductal gray-spinal cord *** aim of the current study was to examine whether the SOM and its receptors are involved in the VLO-induced antinociception in the rat formalin test,and determine whether there was a sex differentiation in the formalin *** After 5%formalin (50μl) was injected subcutaneously into the plantar surface of the hindpaw,the number of times of flinching the hindpaw per 5 min was measured as an index of nociceptive response to observe the effect of microinjection of SOM into the VLO on the nociceptive behavior in different sex *** SOM(10μg/0.5μl)microinjected into the VLO significantly decreased the number of the flinches in either early or later phases in the female rat,and this inhibitory effect was blocked by pre-treatment with its antagonist cyclo-somatostatin(c-SOM,25μg/0.5μl),whereas the SOM had no effect on the formalin-induced flinching behavior in the male ***,c-SOM microinjected alone into the VLO did not influence the flinching behavior in both male and female *** These results suggest that SOM and its receptors are involved in the antinociception in the VLO of the female,but not the male rats in the formalin test.

关键词： Ventrolateral orbital cortex sex difference octreotide cyclo-somatostatin formalin test Flinching rat

Activation of rat primary afferent nociceptive neurons by formaldehyde and mediating roles of the vanilloid receptor TRPV1

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Activation of rat primary afferent nociceptive neurons by fo...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Yong XIAO~1,Li-Juan TIAN~2,Yi-Ru DU~2,Zhuo-Min LU~1,Yao-Qing YU~1,Jun CHEN~(1,2,*) 1 Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,Fourth Military Medical University,Xi’an 710038,China 2 Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China

Background The formalin test is a commonly used animal model of acute and tonic pain,however,the biological actions of formaldehyde(FA,the main ingredient of the formalin solution) on primary nociceptor cells remain *** this report,effects of FA on electrophysiologically-identified primary nociceptor cells were evaluated in vitro and the roles of the vanilloid receptor TRPV1 in FA-produced activation of primary nociceptors were also examined at both cellular and behavioral *** Of 92 acutely dissociated DRG cells recorded by current patch-clamp,34%were discharged after FA application(50 s) with various latencies of the first action potential(Aβ) *** FA-sensitive cells were small to medium-sized(diameters:17.5-37.5μm) and identified electrophysiologically as nociceptor cells due to the unique characteristic of their Aβwaveform with a hump on the repolarizing *** FA-evoked Aβfrequency was concentration-dependent within a range less than 0.004%.Co-application of capsazepine(CPZ,5μM),a competitive antagonist of TRPV1 receptors,could block FA-evoked firing but without influence on the membrane depolarization of all cells tested(n=8).Of another 160 cells examined by confocal calcium imaging,32%(51 cells with diameters:17.5-32.5μm) were shown to respond to FA with an intracellular Ca *** 51 FA-sensitive cells,67%were suppressed by CPZ with the remaining 33%unaffected,suggesting partial involvement of TRPV1 in mediation of the FA-evoked intracellular Ca rise. In comparison with controls(n=5),the FA-evoked inward current recorded by voltage-clamp could also be significantly suppressed by CPZ(n=9).Finally,local effects of two doses of CPZ were also confirmed in the formalin behavioral test and it was shown that the formalin-induced paw flinches in both phase I and phase II were partially but significantly suppressed by ***(1) FA can activate a subpopulation of primary nociceptor cells by membrane depolarization and firing of action

关键词： formalin test nociceptor TRPV1 receptor dorsal root ganglion patch clamp calcium imaging

Antinociceptive effects of analgesic-antitumor peptide（AGAP）,a neurotoxin from the scorpion Buthus martensii Karsch on formalin-induced inflammatory pain through a Mitogen-activated Protein Kinases-dependent Mechanism in mice

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Antinociceptive effects of analgesic-antitumor peptide（AGAP...

第十一届中国生物毒素研究及医药应用年会

作者： Qing-Hong Mao Jia-Ping Ruan Wu-Guang Lu Xue-Ting Cai Juan Ye Jun-Li Cao Peng Cao Department of Anesthesiology Jiangsu Province Institute of Traditional Chinese Medicine Laboratory of Cellular and Molecular Biology Jiangsu Province Institute of Traditional Chinese Medicine Jiangsu Key Laboratory of Anesthesiology Department of AnesthesiologyAffiliated Hospital of Xuzhou Medical College

＜正＞In the present study,we investigated the anti-nociceptive effect and the underlying mechanism of the analgesic-antitumor peptide（AGAP）,a neurotoxin from the scorpion Buthus martensii *** in doses of 0.2,1 and 5 ug was intraplantar（***.） injected before formalin injection 10 min at the same *** suppression by intraplantar injection of AGAP on formalin-induced spontaneous nociceptive behaviors was *** results showed that AGAP could dose-dependent inhibit formalin-induced two-phase spontaneous flinching *** investigate the mechanism of action of treatment with AGAP in inflammatory pain,the expression of peripheral and spinal phosphorylated mitogen-activated protein kinases（phospho-MAPKs） including p-p38,p-ERK and p-JNK were *** found that formalin increased the expression of peripheral and spinal MAPKs,which were prevented by pre-intraplantar injection of AGAP in inflammation pain model in mice. Furthermore,AGAP could also decrease the expression of spinal Fos induced by formalin. The present results indicated that pre-intraplantar injection of AGAP prevented the inflammatory pain induced by formalin through a MAPKs-mediated mechanism in mice.

关键词： AGAP formalin test Mitogen-activated protein kinases c-Fos Inflammatory pain

Roles of TRPC3/6/7 channels in a rat model of inflammatory pain

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Roles of TRPC3/6/7 channels in a rat model of inflammatory p...

中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Jing DING~1,Xiu-Yu CUI~1,Jun CHEN~(1,2,*) 1 Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China 2 Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,Fourth Military Medical University,Xi’an 710038,China

Background:The transient receptor potential canonical(TRPC) channels,which are abundantly expressed in central nervous system(CNS),are Ca permeable nonselective cation channels with different biological *** studies indicated that TRPC1 and TRPC6 channels were likely to be involved in the pathological process of mechanical hyperalgesia and nociceptor *** whether TRPC channels are involved in melittin- or formalin-induced inflammatory nociceptive responses remains ***:In this study,we used behavioral tests combined with pharmacological manipulations to explore the potential roles of TRPC channels in inflammatory pain and ***:In this study,we used the well-established bee-venom(melittin) and formalin *** flinch test was to examine whether TRPC channels are involved in inflammatory paininduced primary *** pain sensitivity of rats was determined by testing paw withdrawal thermal latency(PWTL,s) in response to heat stimuli applied to the injected *** pain hypersensitivity was tested as the paw withdrawal mechanical threshold(PWMT,g).Results:Post- and pre-treatment of the primary injury site with *** of SKF96365,a TRPC3/6/7 antagonist,significantly suppressed the development of inflammatory pain-evoked persistent spontaneous nociception(PSN) and hypersensitivity(thermal and mechanical). Whereas local administration of SKF96365 into the contralateral hindpaw produced no significant effect on any of the pain-associated *** together,these data indicate that TRPC3/6/7 channels might be involved in pathophysiological processing associated with inflammatory ***:In conclusion,we demonstrated for the first time that,although SKF96365 do not affect baseline thermal latency and mechanical nociceptive threshold,it reversed the inflammatory pain-induced spontaneous nociception,heat and mechanical hyperalgesia, indicating that TRPC3/6/7 channels might pla

关键词： TRPC channels melittin formalin test persistent spontaneous nociception primary thermal hyperalgesia primary mechanical hyperalgesia