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Ryozo Oishi - One of the best experts on this subject based on the ideXlab platform.
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Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system
Life Sciences, 2014Co-Authors: Ken Masuguchi, Takehiro Kawashiri, Soichiro Ushio, Ryozo Oishi, Hitomi Watanabe, Nana Ozawa, Haruka Morita, Nobuaki EgashiraAbstract:Abstract Aims Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats. Main methods Oxaliplatin (4 mg/kg) was administered intraperitoneally twice a week for 4 weeks. Cold Hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test. Key findings Repeated injection of oxaliplatin induced Cold Hyperalgesia on day 5 and mechanical allodynia on day 28. A single administration of neurotropin transiently relieved both pain behaviors. The analgesic effect of neurotropin was inhibited by pretreatment with 5-HT 1A , 5-HT 2 , 5-HT 3 , and α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a G i protein inhibitor. Significance These results suggest that neurotropin is effective in relieving oxaliplatin-induced neuropathy, and that G i protein-coupled receptors in the monoaminergic descending pain inhibitory system may be involved in the analgesic effect of neurotropin. Neurotropin may have clinical potential for the treatment of oxaliplatin-induced neuropathies.
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Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.
Journal of Pharmacological Sciences, 2012Co-Authors: Hikaru Sada, Takehiro Kawashiri, Nobuaki Egashira, Soichiro Ushio, Masafumi Shirahama, Ryozo OishiAbstract:Abstract Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not Cold Hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.
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l type ca2 channel blockers prevent oxaliplatin induced Cold Hyperalgesia and trpm8 overexpression in rats
Molecular Pain, 2012Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kentaro Kurobe, Kuniaki Tsutsumi, Yuji Yamashita, Soichiro Ushio, Takahisa Yano, Ryozo OishiAbstract:Background Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced Cold Hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the Cold Hyperalgesia. In the present study, we examined the effects of Ca2+ channel blockers on oxaliplatin-induced Cold Hyperalgesia in rats.
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L type Ca^2+ channel blockers prevent oxaliplatin-induced Cold Hyperalgesia and TRPM8 overexpression in rats
Molecular Pain, 2012Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kentaro Kurobe, Kuniaki Tsutsumi, Yuji Yamashita, Soichiro Ushio, Takahisa Yano, Ryozo OishiAbstract:Background Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced Cold Hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the Cold Hyperalgesia. In the present study, we examined the effects of Ca^2+ channel blockers on oxaliplatin-induced Cold Hyperalgesia in rats. Methods Cold Hyperalgesia was assessed by the acetone test. Oxaliplatin (4 mg/kg), sodium oxalate (1.3 mg/kg) or vehicle was injected i.p. on days 1 and 2. Ca^2+ (diltiazem, nifedipine and ethosuximide) and Na^+ (mexiletine) channel blockers were administered p.o. simultaneously with oxaliplatin or oxalate on days 1 and 2. Results Oxaliplatin (4 mg/kg) induced Cold Hyperalgesia and increased in the transient receptor potential melastatin 8 (TRPM8) mRNA levels in the dorsal root ganglia (DRG). Furthermore, oxalate (1.3 mg/kg) significantly induced the increase in TRPM8 protein in the DRG. Treatment with oxaliplatin and oxalate (500 μM for each) also increased the TRPM8 mRNA levels and induced Ca^2+ influx and nuclear factor of activated T-cell (NFAT) nuclear translocation in cultured DRG cells. These changes induced by oxalate were inhibited by nifedipine, diltiazem and mexiletine. Interestingly, co-administration with nifedipine, diltiazem or mexiletine prevented the oxaliplatin-induced Cold Hyperalgesia and increase in the TRPM8 mRNA levels in the DRG. Conclusions These data suggest that the L type Ca^2+ channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced Cold Hyperalgesia, and that Ca^2+ channel blockers have prophylactic potential for acute neuropathy.
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Goshajinkigan reduces oxaliplatin-induced peripheral neuropathy without affecting anti-tumour efficacy in rodents
European Journal of Cancer, 2011Co-Authors: Soichiro Ushio, Takehiro Kawashiri, Nobuaki Egashira, Hikaru Sada, Masafumi Shirahama, Ken Masuguchi, Ryozo OishiAbstract:Abstract Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused Cold Hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced Cold Hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both Cold Hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced Cold Hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice.
Takehiro Kawashiri - One of the best experts on this subject based on the ideXlab platform.
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Dimethyl fumarate attenuates oxaliplatin-induced peripheral neuropathy without affecting the anti-tumor activity of oxaliplatin in rodents
Biological & Pharmaceutical Bulletin, 2019Co-Authors: Anna Miyagi, Takehiro Kawashiri, Shiori Shimizu, Nao Shigematsu, Daisuke Kobayashi, Takao ShimazoeAbstract:Oxaliplatin has been used as a first choice for colorectal, gastric and pancreatic cancer, but it induces peripheral neuropathies. Dimethyl fumarate (DMF) is an oral drug for multiple sclerosis with neuroprotective effects on oxidative stress. Using both in vivo and in vitro models, we investigated the effects of DMF on oxaliplatin-induced peripheral neuropathy and other side effects, as well as on the anti-tumor activity of oxaliplatin. Repeated intraperitoneal injection of 4 mg/kg oxaliplatin (twice per week for 4 weeks) caused mechanical allodynia (as revealed by the von Frey tests), Cold Hyperalgesia (as revealed by the acetone tests), and axonal degeneration in the sciatic nerve of rats. Co-administration of oral DMF (200 mg/kg, five times per week for 4 weeks) relieved oxaliplatin-induced mechanical allodynia but not Cold Hyperalgesia, and ameliorated axonal degeneration. In addition, DMF did not exacerbate oxaliplatin-induced body weight loss or bone marrow suppression, such as reduction in red blood cells, white blood cells, neutrophils and lymphocytes. Furthermore, DMF did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line (C26, mouse colon carcinoma; HCT116, human colon carcinoma; MKN45, human gastric adenocarcinoma; MIA PaCa-2, human pancreatic carcinoma) or C26-bearing mice. These results suggest that DMF prevents oxaliplatin-induced mechanical allodynia and axonal degeneration without affecting the anti-tumor activity of oxaliplatin. Therefore, DMF may be useful for managing oxaliplatin-induced chronic peripheral neuropathy.
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Prophylactic effect of calcium channel blockers against oxaliplatin-induced acute peripheral neuropathy (1143.8)
The FASEB Journal, 2014Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kuniaki Tsutsumi, Soichiro Ushio, Satohiro MasudaAbstract:Although oxaliplatin (L-OHP) is an important anticancer agent against colorectal cancer, severe acute and chronic peripheral neuropathies are frequently occurred. We peviously reported that oxalate derived from L-OHP is involved in acute Cold Hyperalgesia. In the present study, the mechanism of L-OHP-induced acute neuropathy was examined with the effects of calcium channel blockers in the rat model and primary cultured dorsal root ganglia (DRG). Administration of L-OHP or oxalate to rats induced Cold Hyperalgesia, and increased in transient receptor potential melastatin 8 (TRPM8) mRNA levels in DRG. In addition, the treatment of L-OHP or oxalate induced Ca²⁺ influx and nuclear factor of activated T-cell (NFAT) nuclear translocation as well as up-regulation of the TRPM8 mRNA levels in cultured DRG. These oxalate-induced changes were inhibited by nifedipine, diltiazem and mexiletine. Comparable to the in vitro results, administration of these calcium channel blockers prevented the L-OHP-induced Cold hyperal...
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Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system
Life Sciences, 2014Co-Authors: Ken Masuguchi, Takehiro Kawashiri, Soichiro Ushio, Ryozo Oishi, Hitomi Watanabe, Nana Ozawa, Haruka Morita, Nobuaki EgashiraAbstract:Abstract Aims Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats. Main methods Oxaliplatin (4 mg/kg) was administered intraperitoneally twice a week for 4 weeks. Cold Hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test. Key findings Repeated injection of oxaliplatin induced Cold Hyperalgesia on day 5 and mechanical allodynia on day 28. A single administration of neurotropin transiently relieved both pain behaviors. The analgesic effect of neurotropin was inhibited by pretreatment with 5-HT 1A , 5-HT 2 , 5-HT 3 , and α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a G i protein inhibitor. Significance These results suggest that neurotropin is effective in relieving oxaliplatin-induced neuropathy, and that G i protein-coupled receptors in the monoaminergic descending pain inhibitory system may be involved in the analgesic effect of neurotropin. Neurotropin may have clinical potential for the treatment of oxaliplatin-induced neuropathies.
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Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.
Journal of Pharmacological Sciences, 2012Co-Authors: Hikaru Sada, Takehiro Kawashiri, Nobuaki Egashira, Soichiro Ushio, Masafumi Shirahama, Ryozo OishiAbstract:Abstract Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not Cold Hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.
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l type ca2 channel blockers prevent oxaliplatin induced Cold Hyperalgesia and trpm8 overexpression in rats
Molecular Pain, 2012Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kentaro Kurobe, Kuniaki Tsutsumi, Yuji Yamashita, Soichiro Ushio, Takahisa Yano, Ryozo OishiAbstract:Background Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced Cold Hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the Cold Hyperalgesia. In the present study, we examined the effects of Ca2+ channel blockers on oxaliplatin-induced Cold Hyperalgesia in rats.
Koichi Noguchi - One of the best experts on this subject based on the ideXlab platform.
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An ultrastructural evidence for the expression of transient receptor potential ankyrin 1 (TRPA1) in astrocytes in the rat trigeminal caudal nucleus
Journal of Chemical Neuroanatomy, 2012Co-Authors: Koichi NoguchiAbstract:Abstract The transient receptor potential ankyrin 1 (TRPA1) is implicated in the mechanical and Cold Hyperalgesia following inflammation and nerve injury. Its expression has been presumed to be confined to primary afferent terminals. Here, we show that TRPA1 is expressed in astrocytes in the superficial laminae of the rat trigeminal caudal nucleus by use of electron microscopic immunoperoxidase and immunogold labeling techniques. Immunoreactivity for TRPA1 was consistently observed in somata and process of astrocytes and was weaker than that in presumed nociceptive primary afferent terminals, but increased significantly in the fine process of astrocyte in rats with experimental inflammation of the temporomandibular joint. Thus, we provide ultrastructural evidence that TRPA1 is expressed in astrocytes in the brain stem and propose a novel pathway of its involvement in the central mechanism of inflammatory Hyperalgesia.
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activation of extracellular signal regulated protein kinases 5 in primary afferent neurons contributes to heat and Cold Hyperalgesia after inflammation
Journal of Neurochemistry, 2007Co-Authors: Hirokazu Katsura, Koichi Obata, Toshiyuki Mizushima, Hiroki Yamanaka, Kimiko Kobayashi, Tetsuo Fukuoka, Masafumi Sakagami, Jun Sakurai, Koichi NoguchiAbstract:Heat and Cold Hyperalgesia is a common feature of inflammatory pain. To investigate whether activation of extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1, in primary sensory neurons participates in inflammatory pain, we examined the phosphorylation of ERK5 in the dorsal root ganglion (DRG) after peripheral inflammation. Inflammation induced by complete Freund’s adjuvant produced heat and Cold Hyperalgesia on the ipsilateral hind paw and induced an increase in the phosphorylation of ERK5, mainly in tyrosine kinase A-expressing small- and medium-size neurons. In contrast, there was no change in ERK5 phosphorylation in the spinal dorsal horn. ERK5 antisense, but not mismatch, oligodeoxynucleotide decreased the activation of ERK5 and suppressed inflammation-induced heat and Cold Hyperalgesia. Furthermore, the inhibition of ERK5 blocked the induction of transient receptor potential channel TRPV1 and TRPA1 expression in DRG neurons after peripheral inflammation. Our results show that ERK5 activated in DRG neurons contribute to the development of inflammatory pain. Thus, blocking ERK5 signaling in sensory neurons that has the potential for preventing pain after inflammation.
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Activation of extracellular signal‐regulated protein kinases 5 in primary afferent neurons contributes to heat and Cold Hyperalgesia after inflammation
Journal of Neurochemistry, 2007Co-Authors: Hirokazu Katsura, Koichi Obata, Toshiyuki Mizushima, Hiroki Yamanaka, Kimiko Kobayashi, Tetsuo Fukuoka, Masafumi Sakagami, Jun Sakurai, Koichi NoguchiAbstract:Heat and Cold Hyperalgesia is a common feature of inflammatory pain. To investigate whether activation of extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1, in primary sensory neurons participates in inflammatory pain, we examined the phosphorylation of ERK5 in the dorsal root ganglion (DRG) after peripheral inflammation. Inflammation induced by complete Freund’s adjuvant produced heat and Cold Hyperalgesia on the ipsilateral hind paw and induced an increase in the phosphorylation of ERK5, mainly in tyrosine kinase A-expressing small- and medium-size neurons. In contrast, there was no change in ERK5 phosphorylation in the spinal dorsal horn. ERK5 antisense, but not mismatch, oligodeoxynucleotide decreased the activation of ERK5 and suppressed inflammation-induced heat and Cold Hyperalgesia. Furthermore, the inhibition of ERK5 blocked the induction of transient receptor potential channel TRPV1 and TRPA1 expression in DRG neurons after peripheral inflammation. Our results show that ERK5 activated in DRG neurons contribute to the development of inflammatory pain. Thus, blocking ERK5 signaling in sensory neurons that has the potential for preventing pain after inflammation.
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Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury
The Journal of Neuroscience, 2006Co-Authors: Koichi Obata, Hirokazu Katsura, Hiroki Yamanaka, Kimiko Kobayashi, Tetsuo Fukuoka, Jun Sakurai, Koichi NoguchiAbstract:The p75 neurotrophin receptor (p75NTR) has been implicated in diverse neuronal responses, including survival, cell death, myelination, and inhibition of regeneration. However, the role of p75NTR in neuropathic pain, for which there is currently no effective therapy, has not been explored. Here, we report that the pharmacological blockade of p75NTR in primary sensory neurons reversed neuropathic pain after nerve injury. Nerve injury increased the expression and axonal transport of p75NTR and phosphorylation of TrkA in the uninjured primary afferents. Functional inhibition of p75NTR suppressed injury-induced neuropathic pain and decreased the phosphorylation of TrkA and p38 mitogen-activated protein kinase, and the induction of transient receptor potential channels in dorsal root ganglion (DRG) neurons. Our results show that p75NTR induced in undamaged DRG neurons facilitates TrkA signaling and contributes to heat and Cold Hyperalgesia.
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antisense knock down of trpa1 but not trpm8 alleviates Cold Hyperalgesia after spinal nerve ligation in rats
Experimental Neurology, 2006Co-Authors: Hirokazu Katsura, Koichi Obata, Toshiyuki Mizushima, Hiroki Yamanaka, Kimiko Kobayashi, Tetsuo Fukuoka, Atsushi Tokunaga, Masafumi Sakagami, Koichi NoguchiAbstract:Patients with neuropathic pain frequently experience hypersensitivity to Cold stimulation. However, the underlying mechanisms of this enhanced sensitivity to Cold are not well understood. After partial nerve injury, the transient receptor potential ion channel TRPV1 increases in the intact small dorsal root ganglion (DRG) neurons in several neuropathic pain models. In the present study, we precisely examined the incidence of Cold Hyperalgesia and the changes of TRPA1 and TRPM8 expression in the L4 and L5 DRG following L5 spinal nerve ligation (SNL), because it is likely that the activation of two distinct populations of TRPA1- and TRPM8-expressing small neurons underlie the sensation of Cold. We first confirmed that L5 SNL rats developed Cold Hyperalgesia for more than 14 days after surgery. In the nearby uninjured L4 DRG, TRPA1 mRNA expression increased in trkA-expressing small-to-medium diameter neurons from the 1st to 14th day after the L5 SNL. This upregulation corresponded well with the development and maintenance of nerve injury-induced Cold Hyperalgesia of the hind paw. In contrast, there was no change in the expression of the TRPM8 mRNA/protein in the L4 DRG throughout the 2-week time course of the experiment. In the injured L5 DRG, on the other hand, both TRPA1 and TRPM8 expression decreased over 2 weeks after ligation. Furthermore, intrathecal administration of TRPA1, but not TRPM8, antisense oligodeoxynucleotide suppressed the L5 SNL-induced Cold Hyperalgesia. Our data suggest that increased TRPA1 in uninjured primary afferent neurons may contribute to the exaggerated response to Cold observed in the neuropathic pain model.
Nobuaki Egashira - One of the best experts on this subject based on the ideXlab platform.
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Prophylactic effect of calcium channel blockers against oxaliplatin-induced acute peripheral neuropathy (1143.8)
The FASEB Journal, 2014Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kuniaki Tsutsumi, Soichiro Ushio, Satohiro MasudaAbstract:Although oxaliplatin (L-OHP) is an important anticancer agent against colorectal cancer, severe acute and chronic peripheral neuropathies are frequently occurred. We peviously reported that oxalate derived from L-OHP is involved in acute Cold Hyperalgesia. In the present study, the mechanism of L-OHP-induced acute neuropathy was examined with the effects of calcium channel blockers in the rat model and primary cultured dorsal root ganglia (DRG). Administration of L-OHP or oxalate to rats induced Cold Hyperalgesia, and increased in transient receptor potential melastatin 8 (TRPM8) mRNA levels in DRG. In addition, the treatment of L-OHP or oxalate induced Ca²⁺ influx and nuclear factor of activated T-cell (NFAT) nuclear translocation as well as up-regulation of the TRPM8 mRNA levels in cultured DRG. These oxalate-induced changes were inhibited by nifedipine, diltiazem and mexiletine. Comparable to the in vitro results, administration of these calcium channel blockers prevented the L-OHP-induced Cold hyperal...
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Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system
Life Sciences, 2014Co-Authors: Ken Masuguchi, Takehiro Kawashiri, Soichiro Ushio, Ryozo Oishi, Hitomi Watanabe, Nana Ozawa, Haruka Morita, Nobuaki EgashiraAbstract:Abstract Aims Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats. Main methods Oxaliplatin (4 mg/kg) was administered intraperitoneally twice a week for 4 weeks. Cold Hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test. Key findings Repeated injection of oxaliplatin induced Cold Hyperalgesia on day 5 and mechanical allodynia on day 28. A single administration of neurotropin transiently relieved both pain behaviors. The analgesic effect of neurotropin was inhibited by pretreatment with 5-HT 1A , 5-HT 2 , 5-HT 3 , and α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a G i protein inhibitor. Significance These results suggest that neurotropin is effective in relieving oxaliplatin-induced neuropathy, and that G i protein-coupled receptors in the monoaminergic descending pain inhibitory system may be involved in the analgesic effect of neurotropin. Neurotropin may have clinical potential for the treatment of oxaliplatin-induced neuropathies.
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Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.
Journal of Pharmacological Sciences, 2012Co-Authors: Hikaru Sada, Takehiro Kawashiri, Nobuaki Egashira, Soichiro Ushio, Masafumi Shirahama, Ryozo OishiAbstract:Abstract Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not Cold Hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.
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l type ca2 channel blockers prevent oxaliplatin induced Cold Hyperalgesia and trpm8 overexpression in rats
Molecular Pain, 2012Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kentaro Kurobe, Kuniaki Tsutsumi, Yuji Yamashita, Soichiro Ushio, Takahisa Yano, Ryozo OishiAbstract:Background Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced Cold Hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the Cold Hyperalgesia. In the present study, we examined the effects of Ca2+ channel blockers on oxaliplatin-induced Cold Hyperalgesia in rats.
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L type Ca^2+ channel blockers prevent oxaliplatin-induced Cold Hyperalgesia and TRPM8 overexpression in rats
Molecular Pain, 2012Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kentaro Kurobe, Kuniaki Tsutsumi, Yuji Yamashita, Soichiro Ushio, Takahisa Yano, Ryozo OishiAbstract:Background Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced Cold Hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the Cold Hyperalgesia. In the present study, we examined the effects of Ca^2+ channel blockers on oxaliplatin-induced Cold Hyperalgesia in rats. Methods Cold Hyperalgesia was assessed by the acetone test. Oxaliplatin (4 mg/kg), sodium oxalate (1.3 mg/kg) or vehicle was injected i.p. on days 1 and 2. Ca^2+ (diltiazem, nifedipine and ethosuximide) and Na^+ (mexiletine) channel blockers were administered p.o. simultaneously with oxaliplatin or oxalate on days 1 and 2. Results Oxaliplatin (4 mg/kg) induced Cold Hyperalgesia and increased in the transient receptor potential melastatin 8 (TRPM8) mRNA levels in the dorsal root ganglia (DRG). Furthermore, oxalate (1.3 mg/kg) significantly induced the increase in TRPM8 protein in the DRG. Treatment with oxaliplatin and oxalate (500 μM for each) also increased the TRPM8 mRNA levels and induced Ca^2+ influx and nuclear factor of activated T-cell (NFAT) nuclear translocation in cultured DRG cells. These changes induced by oxalate were inhibited by nifedipine, diltiazem and mexiletine. Interestingly, co-administration with nifedipine, diltiazem or mexiletine prevented the oxaliplatin-induced Cold Hyperalgesia and increase in the TRPM8 mRNA levels in the DRG. Conclusions These data suggest that the L type Ca^2+ channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced Cold Hyperalgesia, and that Ca^2+ channel blockers have prophylactic potential for acute neuropathy.
Takahisa Yano - One of the best experts on this subject based on the ideXlab platform.
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l type ca2 channel blockers prevent oxaliplatin induced Cold Hyperalgesia and trpm8 overexpression in rats
Molecular Pain, 2012Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kentaro Kurobe, Kuniaki Tsutsumi, Yuji Yamashita, Soichiro Ushio, Takahisa Yano, Ryozo OishiAbstract:Background Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced Cold Hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the Cold Hyperalgesia. In the present study, we examined the effects of Ca2+ channel blockers on oxaliplatin-induced Cold Hyperalgesia in rats.
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L type Ca^2+ channel blockers prevent oxaliplatin-induced Cold Hyperalgesia and TRPM8 overexpression in rats
Molecular Pain, 2012Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Kentaro Kurobe, Kuniaki Tsutsumi, Yuji Yamashita, Soichiro Ushio, Takahisa Yano, Ryozo OishiAbstract:Background Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced Cold Hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the Cold Hyperalgesia. In the present study, we examined the effects of Ca^2+ channel blockers on oxaliplatin-induced Cold Hyperalgesia in rats. Methods Cold Hyperalgesia was assessed by the acetone test. Oxaliplatin (4 mg/kg), sodium oxalate (1.3 mg/kg) or vehicle was injected i.p. on days 1 and 2. Ca^2+ (diltiazem, nifedipine and ethosuximide) and Na^+ (mexiletine) channel blockers were administered p.o. simultaneously with oxaliplatin or oxalate on days 1 and 2. Results Oxaliplatin (4 mg/kg) induced Cold Hyperalgesia and increased in the transient receptor potential melastatin 8 (TRPM8) mRNA levels in the dorsal root ganglia (DRG). Furthermore, oxalate (1.3 mg/kg) significantly induced the increase in TRPM8 protein in the DRG. Treatment with oxaliplatin and oxalate (500 μM for each) also increased the TRPM8 mRNA levels and induced Ca^2+ influx and nuclear factor of activated T-cell (NFAT) nuclear translocation in cultured DRG cells. These changes induced by oxalate were inhibited by nifedipine, diltiazem and mexiletine. Interestingly, co-administration with nifedipine, diltiazem or mexiletine prevented the oxaliplatin-induced Cold Hyperalgesia and increase in the TRPM8 mRNA levels in the DRG. Conclusions These data suggest that the L type Ca^2+ channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced Cold Hyperalgesia, and that Ca^2+ channel blockers have prophylactic potential for acute neuropathy.
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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, Nobuaki Egashira, Soichiro Ushio, Takahisa Yano, Hiroaki Ikesue, Hikaru Sada, 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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Prevention of oxaliplatin-induced mechanical allodynia and neurodegeneration by neurotropin in the rat model
European Journal of Pain, 2010Co-Authors: Takehiro Kawashiri, Nobuaki Egashira, Takahisa Yano, Hiroaki Ikesue, Hitomi Watanabe, Yoko Ikegami, Shingo Hirakawa, Yuki Mihara, 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.
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Mexiletine Reverses Oxaliplatin-Induced Neuropathic Pain in Rats
Journal of Pharmacological Sciences, 2010Co-Authors: Nobuaki Egashira, Takehiro Kawashiri, Takahisa Yano, Hiroaki Ikesue, Shingo Hirakawa, Ryozo OishiAbstract:Abstract Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. Mexiletine, an orally available Na + -channel blocker, has widely been used in patients with chronic painful diabetic neuropathy. In the present study, we examined the effect of mexiletine on oxaliplatin-induced neuropathic pain in rats. Mexiletine (100, but not 10 and 30, mg/kg, p.o.) completely reversed both mechanical allodynia and Cold Hyperalgesia induced by oxaliplatin (4 mg/kg, i.p., twice a week). Lidocaine (30, but not 3 and 10, mg/kg, i.p.) also significantly relieved both pain behaviors. These results suggest that mexiletine may be effective in relieving the oxaliplatin-induced neuropathic pain clinically.