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Ryozo Oishi - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of Ca2+/calmodulin-dependent protein kinase II reverses oxaliplatin-induced Mechanical Allodynia in rats.
Molecular pain, 2012Co-Authors: Masafumi Shirahama, Takehiro Kawashiri, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Shota Yamamoto, Ken Masuguchi, Ryozo OishiAbstract:Background Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes severe peripheral neuropathy. We previously reported that oxaliplatin (4 mg/kg, i.p., twice a week) induces Mechanical Allodynia in the late phase in rats, and that spinal NR2B-containig N-methyl-D-aspartate (NMDA) receptors are involved in the oxaliplatin-induced Mechanical Allodynia. In the present study, we investigated the involvement of Ca2+/calmodulin dependent protein kinase II (CaMKII), which is a major intracellular protein kinase and is activated by NMDA receptor-mediated Ca2+ influx, in the oxaliplatin-induced Mechanical Allodynia in rats.
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inhibition of ca2 calmodulin dependent protein kinase ii reverses oxaliplatin induced Mechanical Allodynia in rats
Molecular Pain, 2012Co-Authors: Masafumi Shirahama, Takehiro Kawashiri, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Shota Yamamoto, Ken Masuguchi, Ryozo OishiAbstract:Background Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes severe peripheral neuropathy. We previously reported that oxaliplatin (4 mg/kg, i.p., twice a week) induces Mechanical Allodynia in the late phase in rats, and that spinal NR2B-containig N-methyl-D-aspartate (NMDA) receptors are involved in the oxaliplatin-induced Mechanical Allodynia. In the present study, we investigated the involvement of Ca2+/calmodulin dependent protein kinase II (CaMKII), which is a major intracellular protein kinase and is activated by NMDA receptor-mediated Ca2+ influx, in the oxaliplatin-induced Mechanical Allodynia in rats.
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Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced Mechanical Allodynia in rats.
Molecular Pain, 2011Co-Authors: Yuki Mihara, Takehiro Kawashiri, Takahisa Yano, Hiroaki Ikesue, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Ryozo OishiAbstract:Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and Mechanical Allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA) receptors in oxaliplatin-induced Mechanical Allodynia in rats.
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Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced Mechanical Allodynia in rats
Molecular Pain, 2011Co-Authors: Yuki Mihara, Takehiro Kawashiri, Takahisa Yano, Hiroaki Ikesue, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Ryozo OishiAbstract:Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and Mechanical Allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA) receptors in oxaliplatin-induced Mechanical Allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week) caused Mechanical Allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol) and memantine (1 μmol), NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t.) and ifenprodil (50 mg/kg, p.o.) significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase) but not on Day 5 (early phase). Moreover, we examined the involvement of nitric oxide synthase (NOS) as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS) inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced Mechanical Allodynia.
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Prevention of oxaliplatin-induced Mechanical Allodynia and neurodegeneration by neurotropin in the rat model
European Journal of Pain, 2010Co-Authors: Takehiro Kawashiri, Takahisa Yano, Hiroaki Ikesue, Hitomi Watanabe, Shingo Hirakawa, Yuki Mihara, Yoko Ikegami, Nobuaki Egashira, Ryozo OishiAbstract:Oxaliplatin is a key drug for colorectal cancer, but it causes acute peripheral neuropathy (triggered by cold) and chronic neuropathy (sensory and motor neuropathy) in patients. Neurotropin, a non-protein extract from the inflamed rabbit skin inoculated with vaccinia virus, has been used to treat various chronic pains. In the present study, we investigated the effect of neurotropin on the oxaliplatin-induced neuropathy in rats. Repeated administration of oxaliplatin caused cold hyperalgesia from Day 5 to Day 29 and Mechanical Allodynia from Day 15 to Day 47. Repeated administration of neurotropin relieved the oxaliplatin-induced Mechanical Allodynia but not cold hyperalgesia, and inhibited the oxaliplatin-induced axonal degeneration in rat sciatic nerve. Neurotropin also inhibited the oxaliplatin-induced neurite degeneration in cultured pheochromocytoma 12 (PC12) and rat dorsal root ganglion (DRG) cells. On the other hand, neurotropin did not affect the oxaliplatin-induced cell injury in rat DRG cells. These results suggest that repeated administration of neurotropin relieves the oxaliplatin-induced Mechanical Allodynia by inhibiting the axonal degeneration and it is useful for the treatment of oxaliplatin-induced neuropathy clinically.
Yasushi Kuraishi - One of the best experts on this subject based on the ideXlab platform.
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Prophylactic topical paeoniflorin prevents Mechanical Allodynia caused by paclitaxel in mice through adenosine A1 receptors.
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2016Co-Authors: Tsugunobu Andoh, Nao Kobayashi, Daisuke Uta, Yasushi KuraishiAbstract:Abstract Background The chemotherapeutic agent paclitaxel (PTX) causes refractory peripheral neuropathy as a side effect. Prophylactic oral administration of the traditional herbal medicine Shakuyakukanzoto containing Paeoniae Radix and Glycyrrhizae Radix prevents the development of PTX-induced Mechanical Allodynia in mice via peripheral effects, mostly due to Paeoniae Radix. However, the bioactive component responsible for the prevention of PTX-induced neuropathic pain remains unknown. Purpose To determine whether a monoterpene glycoside paeoniflorin (PF), which is the principal bioactive constituent of Paeoniae Radix, has inhibitory effects on PTX-induced Mechanical Allodynia and investigate the underlying mechanisms. Methods C57BL/6NCr mice received a single intraperitoneal injection of PTX and then were topically administered PF to the planar surface twice daily for 13 days. Mechanical Allodynia was evaluated by the von Frey filament test, peripheral nerve activity was recorded using bipolar electrodes, and demyelination in peripheral nerves was analysed by electron microscopy. Schwann cell line LY-PPB6 pre-treated with PF and then treated with PTX was used to analyse the expression of the transcription factor CHOP, a marker of endoplasmic reticulum (ER) stress, by western blotting. Results PTX caused Mechanical Allodynia and increased both spontaneous and Mechanical stimuli-evoked peripheral nerve activities, whereas repetitive topical application of PF significantly attenuated PTX-induced Allodynia, suppressed saphenous nerve firing, and inhibited demyelination in the plantar nerve. Moreover, in cultured Schwann cells, PF downregulated PTX-induced expression of CHOP, indicating the inhibition of ER stress. The attenuation of Mechanical Allodynia in mice and downregulation of CHOP levels in cell cultures was inhibited by adenosine A 1 receptor (A1R) antagonist 8-cyclopentyl-1,3-diprooylxanrhine, suggesting the involvement of A1R in PF-associated analgesic effects. Conclusion These results suggest that prophylactic topical application of PF is effective in alleviating PTX-induced Mechanical Allodynia by protecting sensory nerves from demyelination via activation of the A1R.
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prophylactic administration of an extract from plantaginis semen and its major component aucubin inhibits Mechanical Allodynia caused by paclitaxel in mice
Journal of Traditional and Complementary Medicine, 2016Co-Authors: Tsugunobu Andoh, Ryo Kitamura, Shizuka Mizoguchi, Daisuke Uta, Mitsuru Kato, Kazufumi Toume, Katsuko Komatsu, Yasushi KuraishiAbstract:The chemotherapeutic agent paclitaxel (PTX) causes peripheral neuropathy as a major dose-limiting side effect, and this peripheral neuropathy is difficult to control. Our previous report showed that prophylactic repetitive administration of goshajinkigan (牛車腎氣丸 niu chē shen qi wan), but not hachimijiogan (八味地黃丸 bā wei di huang wan), which lacks two of the constituents of goshajinkigan, inhibited PTX-induced Mechanical Allodynia in mice. Thus, the herbal medicines Plantaginis Semen (車前子 chē qian zǐ) or Achyranthis Radix (牛膝 niu xī) may contribute to the inhibitory action of goshajinkigan on the exacerbation of PTX-induced Mechanical Allodynia [Andoh et al, J. Tradit. Complement. Med. 2014; 4: 293–297]. Therefore, in this study, we examined whether an extract of Plantaginis Semen (EPS) or Achyranthis Radix (EAR) would relieve PTX-induced Mechanical Allodynia in mice. A single intraperitoneal injection of PTX caused Mechanical Allodynia, which peaked on day 14 after injection. Repetitive oral administration of EPS, but not EAR, starting from the day after PTX injection significantly inhibited the exacerbation of PTX-induced Mechanical Allodynia. Repetitive intraperitoneal injection of aucubin, one of the main components of EPS, starting from the day after PTX injection also significantly reduced PTX-induced Mechanical Allodynia. However, repetitive intraperitoneal injection of geniposide acid (a precursor of aucubin) or catalpol (a metabolite of aucubin) did not prevent the exacerbation of Mechanical Allodynia. These results suggest that prophylactic administration of EPS is effective for preventing the exacerbation of PTX-induced Allodynia. Aucubin may contribute to the inhibitory action of EPS on the exacerbation of PTX-induced Allodynia.
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Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced Mechanical Allodynia in mice.
Pharmacological research, 2016Co-Authors: Ayumi Sakamoto, Tsugunobu Andoh, Yasushi KuraishiAbstract:The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced Mechanical Allodynia in mice. A single intraperitoneal injection of oxaliplatin induced Mechanical Allodynia, which peaked on day 10 after injection. Oxaliplatin-induced Mechanical Allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited Mechanical Allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced Mechanical Allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced Mechanical Allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced Mechanical Allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents.
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Prophylactic administration of an extract from Plantaginis Semen and its major component aucubin inhibits Mechanical Allodynia caused by paclitaxel in mice
Elsevier, 2016Co-Authors: Tsugunobu Andoh, Ryo Kitamura, Shizuka Mizoguchi, Daisuke Uta, Mitsuru Kato, Kazufumi Toume, Katsuko Komatsu, Yasushi KuraishiAbstract:The chemotherapeutic agent paclitaxel (PTX) causes peripheral neuropathy as a major dose-limiting side effect, and this peripheral neuropathy is difficult to control. Our previous report showed that prophylactic repetitive administration of goshajinkigan (牛車腎氣丸 niú chē shèn qì wán), but not hachimijiogan (八味地黃丸 bā wèi dì huáng wán), which lacks two of the constituents of goshajinkigan, inhibited PTX-induced Mechanical Allodynia in mice. Thus, the herbal medicines Plantaginis Semen (車前子 chē qián zǐ) or Achyranthis Radix (牛膝 niú xī) may contribute to the inhibitory action of goshajinkigan on the exacerbation of PTX-induced Mechanical Allodynia [Andoh et al, J. Tradit. Complement. Med. 2014; 4: 293–297]. Therefore, in this study, we examined whether an extract of Plantaginis Semen (EPS) or Achyranthis Radix (EAR) would relieve PTX-induced Mechanical Allodynia in mice. A single intraperitoneal injection of PTX caused Mechanical Allodynia, which peaked on day 14 after injection. Repetitive oral administration of EPS, but not EAR, starting from the day after PTX injection significantly inhibited the exacerbation of PTX-induced Mechanical Allodynia. Repetitive intraperitoneal injection of aucubin, one of the main components of EPS, starting from the day after PTX injection also significantly reduced PTX-induced Mechanical Allodynia. However, repetitive intraperitoneal injection of geniposide acid (a precursor of aucubin) or catalpol (a metabolite of aucubin) did not prevent the exacerbation of Mechanical Allodynia. These results suggest that prophylactic administration of EPS is effective for preventing the exacerbation of PTX-induced Allodynia. Aucubin may contribute to the inhibitory action of EPS on the exacerbation of PTX-induced Allodynia
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Milnacipran inhibits oxaliplatin-induced Mechanical Allodynia through spinal action in mice.
Biological & pharmaceutical bulletin, 2015Co-Authors: Tsugunobu Andoh, Ryo Kitamura, Yasushi KuraishiAbstract:We investigated whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, would have therapeutic effect on oxaliplatin-induced Mechanical Allodynia in mice. A single intraperitoneal injection of oxaliplatin (3 mg/kg) induced Mechanical Allodynia, which peaked on day 10 after injection and almost completely subsided by day 20. Ten days post-oxaliplatin injection, the intraperitoneal administration of milnacipran (3-30 mg/kg) significantly and dose-dependently inhibited the established Mechanical Allodynia. Intrathecal injections of milnacipran (2.1-21 µg/site) also significantly and dose-dependently inhibited Mechanical Allodynia, but intracisternal and intracereboventricular injections at the same doses did not. The present results suggest that milnacipran is effective against oxaliplatin-induced Mechanical Allodynia and that the antiallodynic effect is mainly mediated by actions on the spinal cord.
Seung Kil Hong - One of the best experts on this subject based on the ideXlab platform.
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Loss of spinal mu-opioid receptor is associated with Mechanical Allodynia in a rat model of peripheral neuropathy.
Pain, 2006Co-Authors: Seung Keun Back, Jaehee Lee, Seung Kil HongAbstract:The present study investigated whether the loss of spinal mu-opioid receptors following peripheral nerve injury is related to Mechanical Allodynia. We compared the quantity of spinal mu-opioid receptor and the effect of its antagonists, such as naloxone and CTOP, on pain behaviors in two groups of rats that showed extremely different severity of Mechanical Allodynia 2 weeks following partial injury of tail-innervating nerves. One group (allodynic group) exhibited robust signs of Mechanical Allodynia after the nerve injury, whereas the other group (non-allodynic group) showed little Allodynia despite having suffered the same nerve injury. In addition, we investigated the quantity of spinal mu-opioid receptor and the effect of its antagonists on pain behaviors after the rats had recovered from Mechanical Allodynia 16 weeks following nerve injury. Immunohistochemical and Western blot analyses at 2 weeks after nerve injury indicated that spinal mu-opioid receptor content was more reduced in the allodynic group compared to the non-allodynic group. Intraperitoneal naloxone (2 mg/kg, i.p.) and intrathecal CTOP (10 microg/rat, i.t.) administration dramatically induced Mechanical Allodynia in the non-allodynic group. However, as in naïve animals, neither the loss of spinal mu-opioid receptors nor antagonist-induced Mechanical Allodynia was observed in the rats that had recovered from Mechanical Allodynia. These results suggest that the loss of spinal mu-opioid receptors following peripheral nerve injury is related to Mechanical Allodynia.
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Loss of spinal μ-opioid receptor is associated with Mechanical Allodynia in a rat model of peripheral neuropathy
Pain, 2006Co-Authors: Seung Keun Back, Jaehee Lee, Seung Kil HongAbstract:The present study investigated whether the loss of spinal mu-opioid receptors following peripheral nerve injury is related to Mechanical Allodynia. We compared the quantity of spinal mu-opioid receptor and the effect of its antagonists, such as naloxone and CTOP, on pain behaviors in two groups of rats that showed extremely different severity of Mechanical Allodynia 2 weeks following partial injury of tail-innervating nerves. One group (allodynic group) exhibited robust signs of Mechanical Allodynia after the nerve injury, whereas the other group (non-allodynic group) showed little Allodynia despite having suffered the same nerve injury. In addition, we investigated the quantity of spinal mu-opioid receptor and the effect of its antagonists on pain behaviors after the rats had recovered from Mechanical Allodynia 16 weeks following nerve injury. Immunohistochemical and Western blot analyses at 2 weeks after nerve injury indicated that spinal mu-opioid receptor content was more reduced in the allodynic group compared to the non-allodynic group. Intraperitoneal naloxone (2 mg/kg, i.p.) and intrathecal CTOP (10 microg/rat, i.t.) administration dramatically induced Mechanical Allodynia in the non-allodynic group. However, as in naive animals, neither the loss of spinal mu-opioid receptors nor antagonist-induced Mechanical Allodynia was observed in the rats that had recovered from Mechanical Allodynia. These results suggest that the loss of spinal mu-opioid receptors following peripheral nerve injury is related to Mechanical Allodynia.
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Ascending pathways for Mechanical Allodynia in a rat model of neuropathic pain.
Neuroreport, 2003Co-Authors: Seung Keun Back, Seung Kil Hong, Heung Sik NaAbstract:: To determine what the routes by which Mechanical Allodynia is transmitted following peripheral nerve injury, we assessed the effects of the dorsal column (DC) lesion performed before and 2 weeks after the partial injury of nerves innervating the tail on Mechanical Allodynia. Ipsilateral DC lesion 2 weeks after neuropathic surgery significantly, but not completely, attenuated Mechanical Allodynia. In addition, the DC lesion before peripheral nerve injury did not prevent the generation of Mechanical Allodynia, which was completely blocked by subsequent contralateral hemisection of the spinal cord. However, unlike Mechanical Allodynia, DC lesion did not change thermal Allodynia. These results suggest that the signals for Mechanical Allodynia following peripheral nerve injury are transmitted via the ipsilateral DC and the contralateral pathway(s).
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cold and Mechanical Allodynia in both hindpaws and tail following thoracic spinal cord hemisection in rats time courses and their correlates
Neuroscience Letters, 2003Co-Authors: Young Wook Yoon, Seung Kil Hong, Heung Sik NaAbstract:Abstract We assessed (1) the time courses of cold and Mechanical Allodynia in both hindpaws and the tail, and (2) the relationship of the Allodynia signs between different sites following spinal cord hemisection. Under enflurane anesthesia, rats were subjected to spinal hemisection at T13. The hemisected rats exhibited a significant increase in Mechanical and cold Allodynia signs of both hindpaws and the tail for 22–26 weeks postoperatively. In addition, Mechanical Allodynia signs were significantly correlated not only between the ipsilateral and the contralateral hindpaws, but also between the hindpaws and the tail. These results suggested that cold and Mechanical Allodynia developed extensively and lasted for a long time following spinal cord hemisection, and Mechanical Allodynia shown at different sites may be induced at least in part by common generating mechanisms.
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Effects of morphine on Mechanical Allodynia in a rat model of central neuropathic pain.
Neuroreport, 2003Co-Authors: Junesun Kim, Seung Kil Hong, Ji In Jung, Young Wook YoonAbstract:We examined whether morphine reduced the behavioral signs of neuropathic pain below level induced by T13 spinal hemisection in rats. In order to examine the effect of morphine on the Mechanical Allodynia, morphine alone, morphine with naloxone and saline were administered intraperitoneally and intrathecally and behavioral tests were conducted. In systemic injection, Mechanical Allodynia was reduced only when a higher concentration of morphine (5 mg/kg) was used. Intrathecally injected morphine (0.5, 1, 2, 5 microg) reduced Mechanical Allodynia dose-dependently. It is suggested that systemic morphine has limited effect on Mechanical Allodynia but direct spinal administration of morphine is more effective in controlling central pain following spinal cord injury.
Dong K. Ahn - One of the best experts on this subject based on the ideXlab platform.
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Differential regulation of peripheral IL-1β-induced Mechanical Allodynia and thermal hyperalgesia in rats
Pain, 2014Co-Authors: Min J. Kim, Sang Y. Lee, Kui Y. Yang, Soon Hyeun Nam, Hyun J. Kim, Young Jae Kim, Yong C. Bae, Dong K. AhnAbstract:This study examined the differential mechanisms of Mechanical Allodynia and thermal hyperalgesia after injection of interleukin (IL) 1β into the orofacial area of male Sprague-Dawley rats. The subcutaneous administration of IL-1β produced both Mechanical Allodynia and thermal hyperalgesia. Although a pretreatment with iodoresiniferatoxin (IRTX), a transient receptor potential vanilloid 1 (TRPV1) antagonist, did not affect IL-1β-induced Mechanical Allodynia, it significantly abolished IL-1β-induced thermal hyperalgesia. On the other hand, a pretreatment with D-AP5, an N-methyl-d-aspartate (NMDA) receptor antagonist, and NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, blocked IL-1β-induced Mechanical Allodynia. Pretreatment with H89, a protein kinase A (PKA) inhibitor, blocked IL-1β-induced Mechanical Allodynia but not thermal hyperalgesia. In contrast, pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor, inhibited IL-1β-induced thermal hyperalgesia. Subcutaneous injections of 2% lidocaine, a local anesthetic agent, blocked IL-1β-induced thermal hyperalgesia but not IL-1β-induced Mechanical Allodynia. In the resiniferatoxin (RTX)-pretreated rats, a subcutaneous injection of IL-1β did not produce thermal hyperalgesia due to the depletion of TRPV1 in the primary afferent fibers. Double immunofluorescence revealed the colocalization of PKA with neurofilament 200 (NF200) and of PKC with the calcitonin gene-related peptide (CGRP) in the trigeminal ganglion. Furthermore, NMDA receptor 1 (NR1) and TRPV1 predominantly colocalize with PKA and PKC, respectively, in the trigeminal ganglion. These results suggest that IL-1β-induced Mechanical Allodynia is mediated by sensitized peripheral NMDA/AMPA receptors through PKA-mediated signaling in the large-diameter primary afferent nerve fibers, whereas IL-1β-induced thermal hyperalgesia is mediated by sensitized peripheral TRPV1 receptors through PKC-mediated signaling in the small-diameter primary afferent nerve fibers.
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Blockade of microglial activation reduces Mechanical Allodynia in rats with compression of the trigeminal ganglion
Progress in neuro-psychopharmacology & biological psychiatry, 2011Co-Authors: Seung Ro Han, Min J. Kim, Yong C. Bae, Gwi Y. Yang, Myung H. Ahn, Dong K. AhnAbstract:The present study investigated the role of microglia and p38 MAPK in the development of Mechanical Allodynia in rats with compression of the trigeminal ganglion. Male Sprague-Dawley rats weighing 250-260 g were used. Under pentobarbital sodium anesthesia, the animals were mounted onto a stereotaxic frame and given injections of 4% agar solution (10 μL) to compress the trigeminal ganglion. The air-puff thresholds significantly decreased after compression of the trigeminal ganglion. On postoperative day 14, immunoreactivity to both OX-42 and p-p38 MAPK was up-regulated in the medullary dorsal horn as compared to the sham group. P-p38 MAPK was found to be co-localized with OX-42, but not with NeuN, a neuronal cell marker, or with GFAP, an astroglial cell marker. Intracisternal administration of 100 μg of minocycline significantly inhibited both Mechanical Allodynia and activation of microglia produced by compression of the trigeminal ganglion. Intracisternal administration of 0.1, 1, or 10 μg of SB203580, a p38 MAPK inhibitor, also significantly decreased Mechanical Allodynia and p38 MAPK activation in the trigeminal ganglion-compressed group. These results suggest that activation of p38 MAPK in the microglia is an important step in the development of Mechanical Allodynia in rats with compression of the trigeminal ganglion and that the targeted blockade of microglial p38 MAPK pathway is a potentially important new treatment strategy for trigeminal neuralgia-like nociception.
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Intracisternal and intraperitoneal administration of morphine attenuates Mechanical Allodynia following compression of the trigeminal ganglion in rats.
Journal of orofacial pain, 2010Co-Authors: Hea J Shin, Young Wook Yoon, Yong C. Bae, Gwi Y. Yang, Seong Kyu Han, Dong K. AhnAbstract:Aims To investigate the effects of morphine on Mechanical Allodynia following compression of the trigeminal ganglion in the rat. Methods Experiments were carried out on male Sprague-Dawley rats weighing between 250 and 260 g. For compression, a 4% agar solution (8 microL) was injected into the trigeminal ganglion. In the control group, rats were sham operated without agar injections. The authors evaluated the effects of intraperitoneal or intracisternal administration of morphine on Mechanical Allodynia evoked by air-puff stimulation of the vibrissa pad area 14 days following compression of the trigeminal ganglion. Results Mechanical Allodynia was established within 3 days and lasted beyond postoperative day 24. Intraperitoneal administration of morphine (2 or 5 mg/kg) significantly blocked Mechanical Allodynia ipsilateral to the compression of the trigeminal ganglion. Intraperitoneal administration of morphine also inhibited Mechanical Allodynia on the contralateral side. Moreover, intracisternal administration of morphine (5 microg) strongly suppressed both ipsilateral and contralateral Mechanical Allodynia. The antiallodynic effects of morphine were blocked by pretreatment with naloxone, an opioid receptor antagonist. Conclusion These results suggest that the application of a high dose of morphine may be of great benefit in treating trigeminal neuralgia-like nociception.
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Central Metabotropic Glutamate Receptors Differentially Participate in Interleukin-1β–Induced Mechanical Allodynia in the Orofacial Area of Conscious Rats
The journal of pain : official journal of the American Pain Society, 2006Co-Authors: Chang Y. Jung, Yong C. Bae, Hyo S. Choi, Hyo S. Park, Tae G. Kwon, Dong K. AhnAbstract:Abstract The present study investigated the role of central metabotropic glutamate receptors (mGluRs) in interleukin-1β (IL-1β)–induced Mechanical Allodynia and mirror-image Mechanical Allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230 to 280 g. After administration of 0.01, 0.1, 1, or 10 pg of IL-1β into a subcutaneous area of the vibrissa pad, we examined the withdrawal behavioral responses produced by 10 successive trials of an air-puff ramp pressure applied ipsilaterally or contralaterally to the IL-1β injection site. Subcutaneous injection of IL-1β produced Mechanical Allodynia and mirror-image Mechanical Allodynia in the orofacial area. Intracisternal administration of CPCCOEt, a mGluR1 antagonist, or MPEP, a mGluR5 antagonist, reduced IL-1β–induced Mechanical Allodynia and mirror-image Mechanical Allodynia. Intracisternal administration of APDC, a group II mGluR agonist, or L-AP4, a group III mGluR agonist, reduced both IL-1β–induced Mechanical Allodynia and mirror-image Mechanical Allodynia. The antiallodynic effect, induced by APDC or L-AP4, was blocked by intracisternal pretreatment with LY341495, a group II mGluR antagonist, or CPPG, a group III mGluR antagonist. These results suggest that groups I, II, and III mGluRs differentially modulated IL-1β–induced Mechanical Allodynia, as well as mirror-image Mechanical Allodynia, in the orofacial area. Perspective Central group I mGluR antagonists and groups II and III mGluR agonists modulate IL-1β–induced Mechanical Allodynia and mirror-image Mechanical Allodynia in the orofacial area. Therefore, the central application of group I mGluR antagonists or groups II and III mGluR agonists might be of therapeutic value in treating pain disorder.
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Role of peripheral group I and II metabotropic glutamate receptors in IL-1beta-induced Mechanical Allodynia in the orofacial area of conscious rats.
Pain, 2005Co-Authors: Dong K. Ahn, Chang Y. Jung, Hyo S. Choi, Kwang H Kim, Eun J Lim, Dong H Youn, Yong C. BaeAbstract:The present study investigated the role of peripheral group I and II metabotropic glutamate receptors (mGluRs) in interleukin-1beta (IL-1beta)-induced Mechanical Allodynia in the orofacial area. Experiments were carried out on Sprague-Dawley rats weighing between 230 and 280 g. After subcutaneous administration of 0.01, 0.1, 1, or 10 pg of IL-1beta, we examined withdrawal behavioral responses produced by 10 successive trials of a ramp of air-puffs pressure applied ipsilaterally or contralaterally to the IL-1beta injection site. The thresholds of air puffs were measured 10, 30, 60, 120, or 180 min after 25 microl of IL-1beta was administered through an implanted tube. Subcutaneous injection of IL-1beta produced bilateral Mechanical Allodynia. While the IL-1beta-induced Mechanical Allodynia was blocked by pretreatment with an IL-1 receptor antagonist, the IL-1beta-induced mirror-image Mechanical Allodynia was not blocked by an IL-1 receptor antagonist injected into the contralateral side. Subcutaneous administration of CPCCOEt or LY367385, an mGluR1 antagonist, or MPEP or SIB1893, an mGluR5 antagonist, 10 min prior to injection of IL-1beta abolished IL-1beta-induced Mechanical Allodynia. Pretreatment with APDC or DCG4, a group II mGluR agonist, blocked the IL-1beta-induced Mechanical Allodynia. The anti-allodynic effect induced by APDC was inhibited by pretreatment with LY341495, a group II mGluR antagonist. These results suggest that peripheral group I and II mGluRs participate in IL-1beta-induced Mechanical Allodynia in the orofacial area. Peripheral group I mGluR antagonists blocked the IL-1beta-induced Mechanical Allodynia, while peripheral group II mGluR agonists produced anti-allodynic effects on IL-1beta-induced Mechanical Allodynia in the orofacial area of rats.
Takehiro Kawashiri - One of the best experts on this subject based on the ideXlab platform.
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analgesic effects of sokeikakketsuto on chemotherapy induced Mechanical Allodynia and cold hyperalgesia in rats
Biological & Pharmaceutical Bulletin, 2021Co-Authors: Hiroko Nakamura, Takehiro Kawashiri, Nobuaki Egashira, Daisuke Kobayashi, Mayako Uchida, Takao ShimazoeAbstract:The anticancer agents including oxaliplatin, paclitaxel, and bortezomib cause severe peripheral neuropathy. The Kampo medicine Sokeikakketsuto (SOKT) has been widely used to treat several types of pain. In this study, the analgesic effects of SOKT on oxaliplatin-, paclitaxel-, and bortezomib-induced peripheral neuropathy were investigated in rat models. Rats were treated with oxaliplatin (4 mg/kg, intraperitoneally (i.p.), twice a week for four weeks), paclitaxel (4 mg/kg, i.p., twice a week for two weeks), or bortezomib (0.2 mg/kg, i.p., twice a week for two weeks). SOKT (0.3 or 1.0 g/kg) or duloxetine hydrochloride (30 mg/kg, as a positive control) was administered orally after neuropathy developed. Mechanical Allodynia and cold hyperalgesia were assessed using the von Frey test and the acetone test, respectively. These tests were performed immediately before and 30, 60, 90, and 120 min after the administration of the drugs. Repeated treatment of oxaliplatin induced Mechanical Allodynia and cold hyperalgesia. A single administration of SOKT (1 g/kg, per os (p.o.)), as well as duloxetine, temporarily reversed both the Mechanical Allodynia and the cold hyperalgesia. Repeated administration of paclitaxel and bortezomib also induced the Mechanical Allodynia. SOKT and duloxetine reversed the Mechanical Allodynia caused by bortezomib, but not by paclitaxel. SOKT might have the potential to become a new drug to relieve the symptom of oxaliplatin- or bortezomib-induced peripheral neuropathy.
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Inhibition of Ca2+/calmodulin-dependent protein kinase II reverses oxaliplatin-induced Mechanical Allodynia in rats.
Molecular pain, 2012Co-Authors: Masafumi Shirahama, Takehiro Kawashiri, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Shota Yamamoto, Ken Masuguchi, Ryozo OishiAbstract:Background Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes severe peripheral neuropathy. We previously reported that oxaliplatin (4 mg/kg, i.p., twice a week) induces Mechanical Allodynia in the late phase in rats, and that spinal NR2B-containig N-methyl-D-aspartate (NMDA) receptors are involved in the oxaliplatin-induced Mechanical Allodynia. In the present study, we investigated the involvement of Ca2+/calmodulin dependent protein kinase II (CaMKII), which is a major intracellular protein kinase and is activated by NMDA receptor-mediated Ca2+ influx, in the oxaliplatin-induced Mechanical Allodynia in rats.
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inhibition of ca2 calmodulin dependent protein kinase ii reverses oxaliplatin induced Mechanical Allodynia in rats
Molecular Pain, 2012Co-Authors: Masafumi Shirahama, Takehiro Kawashiri, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Shota Yamamoto, Ken Masuguchi, Ryozo OishiAbstract:Background Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes severe peripheral neuropathy. We previously reported that oxaliplatin (4 mg/kg, i.p., twice a week) induces Mechanical Allodynia in the late phase in rats, and that spinal NR2B-containig N-methyl-D-aspartate (NMDA) receptors are involved in the oxaliplatin-induced Mechanical Allodynia. In the present study, we investigated the involvement of Ca2+/calmodulin dependent protein kinase II (CaMKII), which is a major intracellular protein kinase and is activated by NMDA receptor-mediated Ca2+ influx, in the oxaliplatin-induced Mechanical Allodynia in rats.
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Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced Mechanical Allodynia in rats.
Molecular Pain, 2011Co-Authors: Yuki Mihara, Takehiro Kawashiri, Takahisa Yano, Hiroaki Ikesue, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Ryozo OishiAbstract:Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and Mechanical Allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA) receptors in oxaliplatin-induced Mechanical Allodynia in rats.
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Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced Mechanical Allodynia in rats
Molecular Pain, 2011Co-Authors: Yuki Mihara, Takehiro Kawashiri, Takahisa Yano, Hiroaki Ikesue, Hikaru Sada, Soichiro Ushio, Nobuaki Egashira, Ryozo OishiAbstract:Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and Mechanical Allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA) receptors in oxaliplatin-induced Mechanical Allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week) caused Mechanical Allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol) and memantine (1 μmol), NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t.) and ifenprodil (50 mg/kg, p.o.) significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase) but not on Day 5 (early phase). Moreover, we examined the involvement of nitric oxide synthase (NOS) as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS) inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced Mechanical Allodynia.