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Involvement of ion channels in experimental models of muscle pain
Abstracts / Neuroscience Research 58S (2007) S1–S244
P2-j19 Involvement of ion channels in experimental models of muscle pain Yuko Fujii, Noriyuki Ozaki, Yasuo Sugiura Department of Functional Anatomy and Neuroscience, Nagoya University, Aichi, Japan The roles of ion channels in muscle-mechanical hyperalgesia (M-MH) were examined in the two models of muscle pain. Rats were injected with carrageenan (CI) or subjected to eccentric exercise (ECC) in the gastrocnemius muscle (GM). Randall–Selitto test and von Frey test were performed at the calves to evaluate M-MH. Effects of antagonists on the MH were evaluated. The changes of expression for ion channels in muscle sensory neurons were examined. The MH was observed in both CI and ECC with Randall–Selitto test. Infiltrations of the inflammatory cells in the GM were seen in CI but not in ECC. Antagonists against ASICs and TRPV2, but not TRPV1 showed suppressive effect on the MH after both CI and ECC. Expressions of ASICs and TRPV2 in sensory neurons showed no changes. Although time course and underlying etiology might be different, ASICs and TRPV2 are important components of muscle MH in both CI and ECC model of muscle pain. Research fund: Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (16005947)
Effects of LPA injection into the cisterna magna, trigemP2-j20 inal ganglion and inferior alveolar nerve on the Von Frey test and c-Fos expression Yusuke Sakai, Shinichi Sugiyo, Takashi Shimoda, Aya Masawaki, Masayuki Moritani, Atsushi Yoshida, Motohide Takemura Department of Oral Anatomy and Neurobiology, Osaka University Graduate School of Dentistry, Suita, Japan Lysophosphatidic acid (LPA) is released when nerve is injured and induces demyelination, which causes neuropathic pain. Here, we examined the pain appearance pattern after LPA injection into the cisterna magna (CM), trigeminal ganglion (TG) and inferior alveolar nerve (IAN). The nociceptive face avoidance threshold to mechanical stimulation was examined using Von Frey test. The c-Fos was stained immunohistochemically. After LPA injection into the CM, the lowering of threshold in Von Frey test was observed at 3 and 7 days at masseteric area. When injected LPA into the CM, the mean numbers of c-Fos-immunoreactive neurons increased compared with the control in the principal nucleus (Vp), in the oral nucleus (Vo) and in the Vi/caudal nucleus (Vc) transition zone. These results indicate that the release of LPA in the medullary cord induce neuronal hyperactivity and neuropathic pain.
P2-j21 Tramadol produces nerve conduction block in a manner independent of opioid receptor activation and monoamine uptake inhibition Ryo Katsuki 1,2 , Tsugumi Fujita 2 , Kotaro Mizuta 2 , Tao Liu 2 , Terumasa Nakatsuka 2 , Eiichi Kumamoto 2 1 UMC, Ureshino, Japan; 2 Department of Physiology, Faculty of Medicine, Saga University, Saga, Japan Tramadol is thought to exhibit antinociception through various actions including opioid receptor activation and monoamine uptake inhibition. Although tramadol is also known to have a local anesthetic effect, this action has not been examined yet thoroughly. The present study examined the effects of tramadol and its metabolite mono-O-demethyl-tramadol (M1) on compound action potentials (CAPs) by applying the air-gap method to frog sciatic nerves. Tramadol reduced the peak amplitude of the CAP in a manner independent of naloxone. On the other hand, M1 did not affect CAPs. This tramadol action was not affected by a combination of noradrenaline (NA)-uptake inhibitor desipramine and 5hydroxytryptamine (5-HT)-uptake inhibitor fluoxetine. It is concluded that the inhibitory action of tramadol is not due to opioid receptor activation and also to NA and 5-HT uptake inhibition. The methyl group present in tramadol but not M1 is suggested to play an important role in producing nerve conduction block.
S179
P2-j22 Studies on pain control system (Rept. 67): Opioids regulate sodium currents in rat cultured thalamic neurons
Keisuke Hashimoto 1 , Minoru Narita 1 , Taku Amano 2 , Tsutomu Suzuki 1 1 Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo, Japan; 2 Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Some opioids exert inhibitory effects on the generation and conduction of nerve action potentials in peripheral tissues. However, the specific contribution of opioids in the CNS to the inhibition of voltage-gated sodium channels remains unclear. The present study was designed to investigate the effects of opioids could affect the voltage-gated sodium channels in the rat thalamus. Whole-cell patch-clamp recordings were obtained from cultured thalamic neurons to study the activating sodium current. Bath application of morphine or oxycodone produced a reduction in the peak amplitude of sodium current evoked by a step from a holding potential of −70 mV to a command potential of −20 mV. The present data suggest the possibility that morphine and oxycodone may decrease the activity of neuronal sodium channels in the rat thalamus.
P2-j23
Immunohistochemical changes of pain-related molecules in the spinal dorsal horn of the joint immobilized rat
Kenjiro Tanaka 1 , Yoji Osako 1 , Takahiro Ushida 3 , Tomohiko Nishigami 2 , Kazunari Yuri 1 1 Department of Neurobiology and Anatomy, Kochi Medical School, Kochi, Japan; 2 Department of Orthopaedic Surgery, Kochi Medical School, Kochi, Japan; 3 Multidisciplinary Pain Center, Aichi Medical University, Aichi, Japan The casting (immobilization) may induce not only musculoskeletal motor dysfunction but also pain in the affected limb. It is hypothesized that immobilization may alter nociceptive function of the spinal cord. In order to characterize the casting model, the pain-related molecules were investigated in the spinal dorsal horn.We prepared a rat model of wrist immobilization and analyzed c-Fos, calcitonin gene-related peptide (CGRP), protein kinase C gamma (PKC␥), and glial fibrillary acidic protein (GFAP) expression in the spinal dorsal horn (C7-T1) by using immunohistochemistry. Immunoreactivity of c-Fos, PKC␥, and GFAP was increased in ipsilateral side compared to those in contralateral side. However, immunoreactivity of CGRP was decreased in the ipsilateral side. These results suggested that the casting model showed the feature of neuropathic pain in the spinal dorsal horn.
P2-j24 Studies on pain control system (Rept. 66): Involvement of endogenous opioidergic system in the suppression of the morphine-induced rewarding effect under the neuropathic pain-like state Keiichi Niikura, Minoru Narita, Michiko Narita, Atsushi Nakanura, Naoko Kuzumaki, Kana Nanjo, Kana Kurahashi, Yasuhisa Kobayashi, Masami Suzuki, Tsutomu Suzuki Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan The present study was undertaken to investigate the mechanism of the suppression of the morphine-induced rewarding effect under a neuropathic pain-like state. Here we found that the suppression of the agonist-induced place preference with sciatic nerve ligation was reversed by pre-microinjection of a specific antibody to -endorphin into the ventral tegmental area. Furthermore, the suppression of the morphine-induced rewarding effect under a neuropathic pain-like state was recovered by lacking the pro-opiomelanocortin gene. These findings suggest that the continuous release of -endorphin may implicate in the suppression of the psychological dependence on morphine under a neuropathic pain-like state.
P2-j19 Involvement of ion channels in experimental models of muscle pain Yuko Fujii, Noriyuki Ozaki, Yasuo Sugiura Department of Functional Anatomy and Neuroscience, Nagoya University, Aichi, Japan The roles of ion channels in muscle-mechanical hyperalgesia (M-MH) were examined in the two models of muscle pain. Rats were injected with carrageenan (CI) or subjected to eccentric exercise (ECC) in the gastrocnemius muscle (GM). Randall–Selitto test and von Frey test were performed at the calves to evaluate M-MH. Effects of antagonists on the MH were evaluated. The changes of expression for ion channels in muscle sensory neurons were examined. The MH was observed in both CI and ECC with Randall–Selitto test. Infiltrations of the inflammatory cells in the GM were seen in CI but not in ECC. Antagonists against ASICs and TRPV2, but not TRPV1 showed suppressive effect on the MH after both CI and ECC. Expressions of ASICs and TRPV2 in sensory neurons showed no changes. Although time course and underlying etiology might be different, ASICs and TRPV2 are important components of muscle MH in both CI and ECC model of muscle pain. Research fund: Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (16005947)
Effects of LPA injection into the cisterna magna, trigemP2-j20 inal ganglion and inferior alveolar nerve on the Von Frey test and c-Fos expression Yusuke Sakai, Shinichi Sugiyo, Takashi Shimoda, Aya Masawaki, Masayuki Moritani, Atsushi Yoshida, Motohide Takemura Department of Oral Anatomy and Neurobiology, Osaka University Graduate School of Dentistry, Suita, Japan Lysophosphatidic acid (LPA) is released when nerve is injured and induces demyelination, which causes neuropathic pain. Here, we examined the pain appearance pattern after LPA injection into the cisterna magna (CM), trigeminal ganglion (TG) and inferior alveolar nerve (IAN). The nociceptive face avoidance threshold to mechanical stimulation was examined using Von Frey test. The c-Fos was stained immunohistochemically. After LPA injection into the CM, the lowering of threshold in Von Frey test was observed at 3 and 7 days at masseteric area. When injected LPA into the CM, the mean numbers of c-Fos-immunoreactive neurons increased compared with the control in the principal nucleus (Vp), in the oral nucleus (Vo) and in the Vi/caudal nucleus (Vc) transition zone. These results indicate that the release of LPA in the medullary cord induce neuronal hyperactivity and neuropathic pain.
P2-j21 Tramadol produces nerve conduction block in a manner independent of opioid receptor activation and monoamine uptake inhibition Ryo Katsuki 1,2 , Tsugumi Fujita 2 , Kotaro Mizuta 2 , Tao Liu 2 , Terumasa Nakatsuka 2 , Eiichi Kumamoto 2 1 UMC, Ureshino, Japan; 2 Department of Physiology, Faculty of Medicine, Saga University, Saga, Japan Tramadol is thought to exhibit antinociception through various actions including opioid receptor activation and monoamine uptake inhibition. Although tramadol is also known to have a local anesthetic effect, this action has not been examined yet thoroughly. The present study examined the effects of tramadol and its metabolite mono-O-demethyl-tramadol (M1) on compound action potentials (CAPs) by applying the air-gap method to frog sciatic nerves. Tramadol reduced the peak amplitude of the CAP in a manner independent of naloxone. On the other hand, M1 did not affect CAPs. This tramadol action was not affected by a combination of noradrenaline (NA)-uptake inhibitor desipramine and 5hydroxytryptamine (5-HT)-uptake inhibitor fluoxetine. It is concluded that the inhibitory action of tramadol is not due to opioid receptor activation and also to NA and 5-HT uptake inhibition. The methyl group present in tramadol but not M1 is suggested to play an important role in producing nerve conduction block.
S179
P2-j22 Studies on pain control system (Rept. 67): Opioids regulate sodium currents in rat cultured thalamic neurons
Keisuke Hashimoto 1 , Minoru Narita 1 , Taku Amano 2 , Tsutomu Suzuki 1 1 Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo, Japan; 2 Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Some opioids exert inhibitory effects on the generation and conduction of nerve action potentials in peripheral tissues. However, the specific contribution of opioids in the CNS to the inhibition of voltage-gated sodium channels remains unclear. The present study was designed to investigate the effects of opioids could affect the voltage-gated sodium channels in the rat thalamus. Whole-cell patch-clamp recordings were obtained from cultured thalamic neurons to study the activating sodium current. Bath application of morphine or oxycodone produced a reduction in the peak amplitude of sodium current evoked by a step from a holding potential of −70 mV to a command potential of −20 mV. The present data suggest the possibility that morphine and oxycodone may decrease the activity of neuronal sodium channels in the rat thalamus.
P2-j23
Immunohistochemical changes of pain-related molecules in the spinal dorsal horn of the joint immobilized rat
Kenjiro Tanaka 1 , Yoji Osako 1 , Takahiro Ushida 3 , Tomohiko Nishigami 2 , Kazunari Yuri 1 1 Department of Neurobiology and Anatomy, Kochi Medical School, Kochi, Japan; 2 Department of Orthopaedic Surgery, Kochi Medical School, Kochi, Japan; 3 Multidisciplinary Pain Center, Aichi Medical University, Aichi, Japan The casting (immobilization) may induce not only musculoskeletal motor dysfunction but also pain in the affected limb. It is hypothesized that immobilization may alter nociceptive function of the spinal cord. In order to characterize the casting model, the pain-related molecules were investigated in the spinal dorsal horn.We prepared a rat model of wrist immobilization and analyzed c-Fos, calcitonin gene-related peptide (CGRP), protein kinase C gamma (PKC␥), and glial fibrillary acidic protein (GFAP) expression in the spinal dorsal horn (C7-T1) by using immunohistochemistry. Immunoreactivity of c-Fos, PKC␥, and GFAP was increased in ipsilateral side compared to those in contralateral side. However, immunoreactivity of CGRP was decreased in the ipsilateral side. These results suggested that the casting model showed the feature of neuropathic pain in the spinal dorsal horn.
P2-j24 Studies on pain control system (Rept. 66): Involvement of endogenous opioidergic system in the suppression of the morphine-induced rewarding effect under the neuropathic pain-like state Keiichi Niikura, Minoru Narita, Michiko Narita, Atsushi Nakanura, Naoko Kuzumaki, Kana Nanjo, Kana Kurahashi, Yasuhisa Kobayashi, Masami Suzuki, Tsutomu Suzuki Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan The present study was undertaken to investigate the mechanism of the suppression of the morphine-induced rewarding effect under a neuropathic pain-like state. Here we found that the suppression of the agonist-induced place preference with sciatic nerve ligation was reversed by pre-microinjection of a specific antibody to -endorphin into the ventral tegmental area. Furthermore, the suppression of the morphine-induced rewarding effect under a neuropathic pain-like state was recovered by lacking the pro-opiomelanocortin gene. These findings suggest that the continuous release of -endorphin may implicate in the suppression of the psychological dependence on morphine under a neuropathic pain-like state.