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Vesa K. Kontinen - One of the best experts on this subject based on the ideXlab platform.
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electrophysiologic evidence for increased endogenous gabaergic but not glycinergic inhibitory tone in the rat spinal Nerve Ligation model of neuropathy
Anesthesiology, 2001Co-Authors: Vesa K. Kontinen, Louise C. Stanfa, Amlan Basu, Anthony H. DickensonAbstract:Background Changes in the inhibitory activity mediated by gamma-aminobutyric acid (GABA) and glycine, acting at spinal GABAA receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after Nerve injuries, and blocking either GABAA or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals. Methods In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal Nerve Ligation model of neuropathic pain were studied by comparing the effects of the GABAA-receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats. Results Bicuculline produced a dose-related facilitation of the Adelta-fiber-evoked activity in all study groups and increased C-fiber-mediated activity in the spinal Nerve Ligation group but not in either of the control groups. There were no differences in the effect of bicuculline on low threshold responses between the study groups. The glycine receptor antagonist strychnine did not have a statistically significant effect on any of the parameters studied in any of the control groups. Conclusions These results support the idea of an increased GABAergic inhibitory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after Nerve injury.
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Electrophysiologic evidence for increased endogenous gabaergic but not glycinergic inhibitory tone in the rat spinal Nerve Ligation model of neuropathy.
Anesthesiology, 2001Co-Authors: Vesa K. Kontinen, Louise C. Stanfa, Amlan Basu, Anthony H. Dickenson, Vesa K. Kontinen, Anthony H. DickensonAbstract:Background: Changes in the inhibitory activity mediated by γ-aminobutyric acid (GABA) and glycine, acting at spinal GABA A receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after Nerve injuries, and blocking either GABA A or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals. Methods: In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal Nerve Ligation model of neuropathic pain were studied by comparing the effects of the GABA A -receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats. Results: Bicuculline produced a dose-related facilitation of the Aδ-fiber-evoked activity in all study groups and increased C-fiber-mediated activity in the spinal Nerve Ligation group but not in either of the control groups. There were no differences in the effect of bicuculline on low threshold responses between the study groups. The glycine receptor antagonist strychnine did not have a statistically significant effect on any of the parameters studied in any of the control groups. Conclusions: These results support the idea of an increased GABAergic inhibitory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after Nerve injury.
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EFFECTS OF MIDAZOLAM IN THE SPINAL Nerve Ligation MODEL OF NEUROPATHIC PAIN IN RATS
Journal of The Peripheral Nervous System, 2000Co-Authors: Vesa K. Kontinen, Anthony H. DickensonAbstract:Potential changes in the spinal GABAergic activity after Nerve injury were studied by comparing the effects of systemic administration of the benzodiazepine midazolam on the noxious evoked responses of dorsal horn in rats with spinal Nerve Ligation of neuropathy and control animals. The tight Ligation of the L5 and L6 spinal Nerves was performed in adult male Sprague-Dawley rats and resulting mechanical and cold allodynia were assessed with von Frey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15-18 days after the surgery under halothane anaesthesia using transcutaneous electrical stimulation of the receptive field at three times the C-fibre threshold. The rats in the spinal Nerve Ligation group, but not in the sham-operated control group developed mechanical and cold allodynia. Subcutaneous administration of midazolam 0.1–3.0 mg/kg reduced the A delta-fibre evoked activity in a dose-related manner in all study groups, but the C-fibre evoked activity was significantly reduced only in the spinal Nerve Ligation group. The inhibitory effects of s.c. midazolam were significantly reversed by i.t. administration of flumazenil, suggesting a spinal site of action. Midazolam reduced C-fibre evoked firing significantly more in the spinal Nerve Ligation model than in the non-operated or sham controls. These results indicate changes in the spinal GABAergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain.
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Effects of midazolam in the spinal Nerve Ligation model of neuropathic pain in rats
Pain, 2000Co-Authors: Vesa K. Kontinen, Anthony H. DickensonAbstract:Abstract Potential changes in the spinal GABAergic activity after Nerve injury were studied by comparing the effects of systemic administration of the benzodiazepine midazolam on the noxious evoked responses of dorsal horn in rats with spinal Nerve Ligation of neuropathy and control animals. The tight Ligation of the L 5 and L6 spinal Nerves was performed in adult male Sprague–Dawley rats and resulting mechanical and cold allodynia were assessed with von Frey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15–18 days after the surgery under halothane anaesthesia using transcutaneous electrical stimulation of the receptive field at three times the C-fibre threshold. The rats in the spinal Nerve Ligation group, but not in the sham-operated control group developed mechanical and cold allodynia. Subcutaneous administration of midazolam 0.1–3.0 mg/kg reduced the A δ -fibre evoked activity in a dose-related manner in all study groups, but the C-fibre evoked activity was significantly reduced only in the spinal Nerve Ligation group. The inhibitory effects of s.c. midazolam were significantly reversed by i.t. administration of flumazenil, suggesting a spinal site of action. Midazolam reduced C-fibre evoked firing significantly more in the spinal Nerve Ligation model than in the non-operated or sham controls. These results indicate changes in the spinal GABAergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain.
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EFFECTS OF MIDAZOLAM IN THE SPINAL Nerve Ligation MODEL OF NEUROPATHIC PAIN IN RATS
Journal of the Peripheral Nervous System, 2000Co-Authors: Vesa K. Kontinen, Ah DickensonAbstract:Potential changes in the spinal GABAergic activity after Nerve injury were studied by comparing the effects of systemic administration of the benzodiazepine midazolam on the noxious evoked responses of dorsal horn in rats with spinal Nerve Ligation of neuropathy and control animals. The tight Ligation of the L-5 and L6 spinal Nerves was performed in adult male Sprague-Dawley rats and resulting mechanical and cold allodynia were assessed with von Prey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15-18 days after the surgery under halothane anaesthesia using transcutaneous electrical stimulation of the receptive field at three times the C-fibre threshold. The rats in the spinal Nerve Ligation group, but not in the sham-operated control group developed mechanical and cold allodynia. Subcutaneous administration of midazolam 0.1-3.0 mg/kg reduced the A delta-fibre evoked activity in a dose-related manner in all study groups, but the C-fibre evoked activity was significantly reduced only in the spinal Nerve Ligation group. The inhibitory effects of s.c. midazolam were significantly reversed by i.t. administration of flumazenil, suggesting a spinal site of action. Midazolam reduced C-fibre evoked firing significantly more in the spinal Nerve Ligation model than in the non-operated or sham controls. These results indicate changes in the spinal GABAergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved
Anthony H. Dickenson - One of the best experts on this subject based on the ideXlab platform.
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Electrophysiologic evidence for increased endogenous gabaergic but not glycinergic inhibitory tone in the rat spinal Nerve Ligation model of neuropathy.
Anesthesiology, 2001Co-Authors: Vesa K. Kontinen, Louise C. Stanfa, Amlan Basu, Anthony H. Dickenson, Vesa K. Kontinen, Anthony H. DickensonAbstract:Background: Changes in the inhibitory activity mediated by γ-aminobutyric acid (GABA) and glycine, acting at spinal GABA A receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after Nerve injuries, and blocking either GABA A or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals. Methods: In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal Nerve Ligation model of neuropathic pain were studied by comparing the effects of the GABA A -receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats. Results: Bicuculline produced a dose-related facilitation of the Aδ-fiber-evoked activity in all study groups and increased C-fiber-mediated activity in the spinal Nerve Ligation group but not in either of the control groups. There were no differences in the effect of bicuculline on low threshold responses between the study groups. The glycine receptor antagonist strychnine did not have a statistically significant effect on any of the parameters studied in any of the control groups. Conclusions: These results support the idea of an increased GABAergic inhibitory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after Nerve injury.
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electrophysiologic evidence for increased endogenous gabaergic but not glycinergic inhibitory tone in the rat spinal Nerve Ligation model of neuropathy
Anesthesiology, 2001Co-Authors: Vesa K. Kontinen, Louise C. Stanfa, Amlan Basu, Anthony H. DickensonAbstract:Background Changes in the inhibitory activity mediated by gamma-aminobutyric acid (GABA) and glycine, acting at spinal GABAA receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after Nerve injuries, and blocking either GABAA or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals. Methods In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal Nerve Ligation model of neuropathic pain were studied by comparing the effects of the GABAA-receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats. Results Bicuculline produced a dose-related facilitation of the Adelta-fiber-evoked activity in all study groups and increased C-fiber-mediated activity in the spinal Nerve Ligation group but not in either of the control groups. There were no differences in the effect of bicuculline on low threshold responses between the study groups. The glycine receptor antagonist strychnine did not have a statistically significant effect on any of the parameters studied in any of the control groups. Conclusions These results support the idea of an increased GABAergic inhibitory tone in the spinal cord of neuropathic rats, possibly as compensation for increased excitability after Nerve injury.
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EFFECTS OF MIDAZOLAM IN THE SPINAL Nerve Ligation MODEL OF NEUROPATHIC PAIN IN RATS
Journal of The Peripheral Nervous System, 2000Co-Authors: Vesa K. Kontinen, Anthony H. DickensonAbstract:Potential changes in the spinal GABAergic activity after Nerve injury were studied by comparing the effects of systemic administration of the benzodiazepine midazolam on the noxious evoked responses of dorsal horn in rats with spinal Nerve Ligation of neuropathy and control animals. The tight Ligation of the L5 and L6 spinal Nerves was performed in adult male Sprague-Dawley rats and resulting mechanical and cold allodynia were assessed with von Frey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15-18 days after the surgery under halothane anaesthesia using transcutaneous electrical stimulation of the receptive field at three times the C-fibre threshold. The rats in the spinal Nerve Ligation group, but not in the sham-operated control group developed mechanical and cold allodynia. Subcutaneous administration of midazolam 0.1–3.0 mg/kg reduced the A delta-fibre evoked activity in a dose-related manner in all study groups, but the C-fibre evoked activity was significantly reduced only in the spinal Nerve Ligation group. The inhibitory effects of s.c. midazolam were significantly reversed by i.t. administration of flumazenil, suggesting a spinal site of action. Midazolam reduced C-fibre evoked firing significantly more in the spinal Nerve Ligation model than in the non-operated or sham controls. These results indicate changes in the spinal GABAergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain.
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Effects of midazolam in the spinal Nerve Ligation model of neuropathic pain in rats
Pain, 2000Co-Authors: Vesa K. Kontinen, Anthony H. DickensonAbstract:Abstract Potential changes in the spinal GABAergic activity after Nerve injury were studied by comparing the effects of systemic administration of the benzodiazepine midazolam on the noxious evoked responses of dorsal horn in rats with spinal Nerve Ligation of neuropathy and control animals. The tight Ligation of the L 5 and L6 spinal Nerves was performed in adult male Sprague–Dawley rats and resulting mechanical and cold allodynia were assessed with von Frey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15–18 days after the surgery under halothane anaesthesia using transcutaneous electrical stimulation of the receptive field at three times the C-fibre threshold. The rats in the spinal Nerve Ligation group, but not in the sham-operated control group developed mechanical and cold allodynia. Subcutaneous administration of midazolam 0.1–3.0 mg/kg reduced the A δ -fibre evoked activity in a dose-related manner in all study groups, but the C-fibre evoked activity was significantly reduced only in the spinal Nerve Ligation group. The inhibitory effects of s.c. midazolam were significantly reversed by i.t. administration of flumazenil, suggesting a spinal site of action. Midazolam reduced C-fibre evoked firing significantly more in the spinal Nerve Ligation model than in the non-operated or sham controls. These results indicate changes in the spinal GABAergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain.
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Enlargement of the receptive field size to low intensity mechanical stimulation in the rat spinal Nerve Ligation model of neuropathy.
Experimental neurology, 2000Co-Authors: Rie Suzuki, Vesa K. Kontinen, Elizabeth A. Matthews, Emma L. Williams, Anthony H. DickensonAbstract:One characteristic of plasticity after peripheral tissue or Nerve damage is receptive field reorganization, and enlargement of receptive field size has been suggested to occur in certain models of neuropathic pain. The aim of the present study was to explore whether enlargement of neuronal receptive fields could contribute to the mechanical allodynia found on the ipsilateral paw in the spinal Nerve Ligation model of neuropathy. After Ligation of L(5)-L(6) spinal Nerves, all rats developed behavioral signs of mechanical allodynia, while the sham-operated control group displayed no such changes. The characteristics of the evoked responses of the neurones recorded in the dorsal horn of the rats were similar between the spinal Nerve Ligation, the sham operated control group, and the nonoperated control group, except for spontaneous activity, which was significantly increased in the spinal Nerve Ligation group. The mean size of the receptive field on the ipsilateral hindpaw, mapped using low-intensity stimulation with 9-g von Frey hair, was significantly increased in the spinal Nerve Ligation group, as compared to the sham-operated group. No significant difference was seen with 15- or 75-g von Frey hairs. The distribution of the receptive fields over the plantar surface of the paw was similar between the study groups. The enlargement of receptive field for non-noxious touch could be an indication of central sensitization in this model.
Myung Ha Yoon - One of the best experts on this subject based on the ideXlab platform.
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Synergistic anti-allodynic effect between intraperitoneal thalidomide and morphine on rat spinal Nerve Ligation- induced neuropathic pain
Korean journal of anesthesiology, 2013Co-Authors: Hyung Gon Lee, Myung Ha Yoon, Woong Mo Kim, A Reum Park, Jeong Il ChoiAbstract:Background Thalidomide has been recognized as having an anti-allodynic effect against neuropathic pain induced by spinal Nerve Ligation. Its clinical beneficial effects are mainly derived from its immune-modulating property, which is known to influence the analgesic action of morphine. The possible characteristics of systemic interactions between thalidomide and morphine in the context of spinal Nerve Ligation-induced neuropathic pain were examined in rats. Methods Neuropathic pain was induced by Ligation of the L5/6 spinal Nerves in male Sprague-Dawley rats and mechanical allodynia was assessed using von Frey filaments. The ED50 was calculated for thalidomide and for morphine, and the mixture of both drugs was intraperitoneally administered at different doses of ED50 of each drug (1/8, 1/4, 1/2, 1/1 of ED50) to obtain the experimental ED50 value for the combination of thalidomide and morphine. Isobolographic analysis was used to evaluate the characteristics of drug interactions between morphine and thalidomide. Results The ED50 of thalidomide was three-fold higher than that of morphine. The experimental ED50 value of the mixture of thalidomide and morphine was significantly lower than the calculated theoretical ED50 value. Isobolographic analysis revealed a synergistic interaction for anti-allodynic effect after intraperitoneal delivery of the thalidomide-morphine mixture. Conclusions These results suggest that thalidomide acts synergistically with morphine to produce an anti-allodynic effect in neuropathic pain induced by spinal Nerve Ligation in rats. Thus, the combination of thalidomide with morphine may be one of the useful strategies in the management of neuropathic pain.
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Antiallodynic Effect of Thalidomide and Morphine on Rat Spinal Nerve Ligation-induced Neuropathic Pain.
The Korean Journal of Pain, 2010Co-Authors: Jeong Il Choi, Myung Ha YoonAbstract:Background: Tumor necrosis factor-alpha and other proinflammatory cytokines are becoming well recognized as key mediators in the pathogenesis of many types of neuropathic pain. Thalidomide has profound immunomodulatory actions in addition to their originally intended pharmacological actions. There has been debate on the analgesic efficacy of opioids in neuropathic pain. The aim of this study was to investigate the effect of thalidomide and morphine on a spinal Nerve Ligation model in rats. Methods: Male Sprague-Dawley rats weighing 100−120 g were used. Lumbar (L) 5 and 6 spinal Nerve Ligations were performed to induce neuropathic pain. For assessment of mechanical allodynia, mechanical stimulus using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of intraperitoneal thalidomide (6.25, 12.5, 25 and 50 mg/kg, respectively) and morphine (3 and 10 mg/kg, respectively) were examined on a withdrawal threshold evoked by spinal Nerve Ligation. Results: After L5 and 6 spinal Nerve Ligation, paw withdrawal thresholds on the ipsilateral side were significantly decreased compared with pre-operative baseline and with those in the sham-operated group. Intraperitoneal thalidomide and morphine significantly increased the paw withdrawal threshold compared to controls and produced dose-responsiveness. Conclusions: Systemic thalidomide and morphine have antiallodynic effect on neuropathic pain induced by spinal Nerve Ligation in rat. These results suggest that morphine and thalidomide may be alternative therapeutic approaches for neuropathic pain. (Korean J Pain 2010; 23: 172-178)
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Potentiation of morphine antiallodynic efficacy by ACPT-III, a group III metabotropic glutamate receptor agonist, in rat spinal Nerve Ligation-induced neuropathic pain.
Pharmacology biochemistry and behavior, 2010Co-Authors: Hyung Gon Lee, Sung Keun Park, Myung Ha YoonAbstract:Despite the importance of spinal metabotropic glutamate receptors (mGluRs) and opioid receptors in nociceptive processing, the roles of these receptors in the modulation of neuropathic pain at the spinal level have not been thoroughly investigated. The purpose of this study was to investigate the effects of spinal mGluR agents and opioids (morphine) on neuropathic pain. Male Sprague-Dawley rats underwent L5 and L6 spinal Nerve Ligation to induce neuropathic pain and intrathecal catheterization for drug administration. A paw-withdrawal threshold to mechanical stimulus was measured using the "up and down" method. When administered intrathecally, neither Group I mGluR antagonists nor Group II or III agonists modified the withdrawal threshold after spinal Nerve Ligation. Intrathecal administration of morphine dose-dependently increased the withdrawal threshold. Whereas ACPT-III, a Group III mGluR agonist, enhanced the antiallodynic action of morphine, other mGluR agents did not. Collectively, mGluRs may not directly modulate the processing of spinal Nerve Ligation-induced neuropathic pain at the spinal level. However, Group III mGluR agonists in the spinal cord may indirectly contribute to the potentiation of morphine antiallodynia, indicating that these agonists might be used as adjuvants for spinal morphine.
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The Antinociceptive Effect of Thalidomide on Spinal Nerve Ligation-Induced Pain in Rat
2010Co-Authors: Hyung Gon Lee, Woong Mo Kim, Myung Ha YoonAbstract:Background: Tumor necrosis factor-alpha (TNF-[start_en]03B1;) and other pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) are becoming well recognized as a key mediators in the pathogenesis of many types of neuropathic pain. This study examined the antinociceptive effect of thalidomide, which have profound immunomodulatory effects on spinal Nerve Ligation model in rat. Methods: Male SD rats weighing 100-120g were used. L5 and L6 spinal Nerves Ligation was performed for induction of neuropathic pain. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw and measured a withdrawal threshold. The effects of intrathecal and intraperitoneal thalidomide were examined on a withdrawal threshold evoked by spinal Nerve Ligation. Results: After L5,6 spinal Nerve Ligation, the paw withdrawal thresholds on the ipsilateral side were significantly decreased compared with pre-operative baseline and with those in sham-operated group. Intraperitoneal thalidomide reduced significantly the paw withdrawal threshold compared to control and produced doseresponsiveness. But, intrathecal thalidomide did not alter the withdrawal threshold in the injured paw.
Tsutomu Suzuki - One of the best experts on this subject based on the ideXlab platform.
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Increased phosphorylated-μ-opioid receptor immunoreactivity in the mouse spinal cord following sciatic Nerve Ligation
Neuroscience letters, 2004Co-Authors: Minoru Narita, Naoko Kuzumaki, Masami Suzuki, Michiko Narita, Mitsuaki Yamazaki, Yoshinori Yajima, Tsutomu SuzukiAbstract:The present study was designed to determine whether a state of neuropathic pain induced by sciatic Nerve Ligation could alter phosphorylated-μ-opioid receptor-like immunoreactivity in the superficial dorsal horn of the mouse spinal cord. Mice with sciatic Nerve Ligation exhibited a significant suppression of the morphine-induced antinociception. Under this condition, phosphorylated-μ-opioid receptor-like immunoreactivity was clearly increased on the ipsilateral side in the superficial laminae of the L5 lumbar spinal dorsal horn in Nerve-ligated mice. These findings suggest that the phosphorylation of the μ-opioid receptor in the spinal cord under a neuropathic pain-like state may, at least in part, contribute to the reduction in the antinociceptive effect produced by morphine in the mouse.
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Change in the expression of c-fos in the rat brain following sciatic Nerve Ligation.
Neuroscience letters, 2003Co-Authors: Minoru Narita, Michiko Narita, Yoshinori Yajima, Satoru Ozaki, Yuya Ise, Tsutomu SuzukiAbstract:A little or none is known about the direct evidence for the possible change in the expression of c-fos at the supraspinal level after Nerve injury. Therefore, the present study was designed to investigate the level of c-fos in some brain regions following sciatic Nerve Ligation in the rat. Immunoblot analysis clearly showed that the levels of c-fos in the rat frontal cortex, thalamus and periaqueductal gray matter were significantly increased, whereas it was significantly decreased in the nucleus accumbens and ventral tegmental area. Under these conditions, the levels of c-fos in the rat amygdala, hippocampus and hypothalamus were not changed. These results provide direct evidence that the neuropathic pain-like state causes a substantial change in the expression of c-fos in the rat brain.
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Involvement of spinal protein kinase C in thermal hyperalgesia evoked by partial sciatic Nerve Ligation, but not by inflammation in the mouse.
European journal of pharmacology, 2000Co-Authors: M Ohsawa, Minoru Narita, Tsutomu Suzuki, H Mizoguchi, L F TsengAbstract:Activation of several protein kinases contributes to the development of hyperalgesia evoked by injuries. The present study was designed to investigate the role of protein kinase C in the spinal cord in thermal hyperalgesia evoked by sciatic Nerve Ligation or by intraplantar injection of complete Freund's adjuvant. The paw withdrawal latency on the ipsilateral side, but not on the contralateral side, was markedly decreased after sciatic Nerve Ligation. Intraplantar injection of complete Freund's adjuvant also caused markedly decreases of the paw withdrawal latency. Intrathecal pretreatment with protein kinase C inhibitor calphostin C (100 and 250 ng) attenuated the decrease of the paw withdrawal latency evoked by sciatic Nerve Ligation. In contrast, the decrease of the paw withdrawal latency evoked by inflammation was only slightly attenuated by intrathecal pretreatment with calphostin C. The results indicate that protein kinase C in the spinal cord is involved in the development of the thermal hyperalgesia evoked by Nerve Ligation and is much less involved in the thermal hyperalgesia by complete Freund's adjuvant's-induced inflammation.
Eija Kalso - One of the best experts on this subject based on the ideXlab platform.
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Behavioural measures of depression and anxiety in rats with spinal Nerve Ligation-induced neuropathy.
Pain, 1999Co-Authors: Vesa K. Kontinen, Antti Pertovaara, Timo Kauppila, Sami Paananen, Eija KalsoAbstract:The behaviour of rats with spinal Nerve Ligation-induced neuropathic pain was studied using tests developed to measure depression and anxiety. Adult male Sprague–Dawley rats were tested with the open field test, elevated plus maze, two compartment test and forced swimming test. Spontaneous motility was measured in a photocell observation box. Mechanical sensitivity was tested with von Frey hairs and cold sensitivity with the acetone drop test. The L5–6 spinal Nerves were ligated or a sham operation was performed and the rats were followed for 2 weeks before the same set of tests were repeated. Most of the neuropathy operated rats had mechanical and cold allodynia. With post-injury there was a significant decrease in the activity in the open field test and motility box tests, when compared with the pre-injury results. In the elevated plus maze test there was a significant reduction in the motility, but there was no change in the time spent in the closed wings. In the two compartment test there were no significant differences between the pre- and post-injury results. There were no differences between the rats with spinal Nerve Ligation injury and the sham operated rats in any of the tests. The results were also comparable when rats that developed a high degree of neuropathy were compared with the rats with low degree of neuropathy and the sham operated group. In conclusion, spinal Nerve Ligation injury of the spinal Nerves L5–6 induces mechanical and cold allodynia, but it does not seem to produce general suffering or measurable anxiety to the animals. Furthermore, tests for anxiety and depression were not able to predict which animals were vulnerable to express symptoms of neuropathic pain after Nerve injury.
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Endogenous noradrenergic tone controls symptoms of allodynia in the spinal Nerve Ligation model of neuropathic pain.
European journal of pharmacology, 1999Co-Authors: Vesa K. Kontinen, Eija KalsoAbstract:Endogenous inhibitory controls were studied in the spinal Nerve Ligation model of neuropathic pain. Atipamezole, a selective alpha2-adrenoceptor antagonist, produced both mechanical and cold allodynia in those rats which had not developed clear neuropathic symptoms. The same doses (50 microg i.t. or 1 mg/kg s.c.) did not increase the severity of symptoms in rats which had developed them. The opioid receptor antagonist naloxone (20 microg i.t. or 1 mg/kg s.c.) had no effect on the neuropathic symptoms. These results indicate that mechanical and cold allodynia are under endogenous noradrenergic rather than opioidergic control in this model of neuropathic pain.
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Chronic spinal Nerve Ligation induces changes in response characteristics of nociceptive spinal dorsal horn neurons and in their descending regulation originating in the periaqueductal gray in the rat.
Experimental neurology, 1997Co-Authors: Antti Pertovaara, Vesa K. Kontinen, Eija KalsoAbstract:We studied whether a chronic neuropathy induced by unilateral spinal Nerve Ligation changes the response characteristics of spinal dorsal horn wide-dynamic range (WDR) neurons or their periaqueductal gray (PAG)-induced descending modulation. Experiments were performed in rats with behaviorally demonstrated allodynia induced by spinal Nerve Ligation and in a group of nonneuropathic control rats. The stimulus-response functions of WDR neurons for mechanical and thermal stimuli and the modulation of their peripherally evoked responses by electrical stimulation of the PAG were determined under pentobarbital anesthesia. The results showed that neuropathy caused a significant leftward shift in stimulus-response functions for mechanical stimuli. In contrast, stimulus-response functions for noxious heat stimuli in the neuropathic limb were, if anything, shifted rightward, although this shift was short of statistical significance. In neuropathic rats, PAG stimulation produced a significantly stronger attenuation of spinal neuronal responses induced by noxious heat in the unoperated than in the operated side. At the intensity that produced attenuation of noxious heat stimuli, PAG stimulation did not produce any significant change in spinal neuronal responses evoked by mechanical stimuli either from the operated or the nonoperated hindlimb of the neuropathic rats. Spontaneous activity of WDR neurons was higher in the operated side of neuropathic rats than in control rats. Afterdischarges evoked by peripheral stimuli were observed in 1/16 of the WDR neurons ipsilateral to spinal Nerve Ligation and not at all in other experimental groups. The WDR neurons studied were not activated by innocuous or noxious cold stimuli. The results indicate that spinal Nerve Ligation induces increased spontaneous activity and enhanced responses to mechanical stimuli in the spinal dorsal horn WDR neurons, whereas noxious heat-evoked responses are not significantly changed or if anything, attenuated. Moreover, the inhibition of noxious heat stimuli by PAG stimulation is attenuated in the neuropathic side. It is proposed that the observed changes in the response characteristics of the spinal dorsal horn WDR neurons and in their descending modulation may contribute to the neuropathic symptoms in these animals.
