Mechanisms of endogenous cannabinoid receptor activation-induced analgesia and its application to intractable cancer pain

• Project/Area Number: 19390407
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Sapporo Medical University
• Principal Investigator: KAWAMATA Tomoyuki Sapporo Medical University, 医学部, 准教授 (80336388)
• Co-Investigator(Kenkyū-buntansha): WATANABE Masahiko 北海道大学, 医学研究科, 教授 (70210945) ; NARIMATSU Eichi 札幌医科大学, 医学部, 准教授 (70295343)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2007: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
• Keywords: がん疼痛 / 大麻 / 鎮痛 / 骨がん / 疼痛 / カンナビノイド / 脊髄

Research Abstract

This study was planned to clarify the mechanism of CB1 activation-induced analgesia the analgesic effects of CB1 on bone cancer pain. Immunohistochemical experiments showed that, although mu opioid receptor 1 expression was reduced in the superficial dorsal horn, CB1 expression was preserved. In addition, CB1 was mainly expressed in the axon terminals of spinal excitatory interneurons. Spinal CB1 activation reduced bone cancer-related pain behaviors, including behaviors related to spontaneous pain and movement-evoked pain. Spinal CB1 activation reduced bone cancer-related pain behavior. Presynaptic inhibition may contribute to the analgesic effects of spinal CB1 activation. These findings may lead to novel strategies for the treatment of bone cancer pain.

Research Products

• [Journal Article] Role of satellite cell-derived L-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy. (2011)
  • Author(s): Kiya T, Kawamata T, Namiki A, Yamakage M
  • Journal Title: Neuroscience 174 Pages: 190-199
  • Peer Reviewed
• [Journal Article] Reduction of bone cancer pain by CB1 activation and TRPV1 inhibition. (2010)
  • Author(s): Kawamata T, Niiyama Y, Yamamoto J, Furuse S
  • Journal Title: J Anesth 24 Pages: 328-332
  • NAID: 10027266825
  • Peer Reviewed
• [Journal Article] Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord. (2010)
  • Author(s): Yanagisawa Y, Furue H, Kawamata T, Uta D, Yamamoto J, Furuse S, Katafuchi T, Imoto K, Iwamoto Y, Yoshimura M
  • Journal Title: Mol Pain 6 Pages: 38-38
  • Peer Reviewed
• [Journal Article] Molecular signaling of pruritus induced by endothelin-1 in mice. (2010)
  • Author(s): Liang J, Kawamata T, Ji W
  • Journal Title: Exp Biol Med 235 Pages: 1300-1305
  • Peer Reviewed
• [Journal Article] Effects of atropine and pralidoxime on neuronal actions of paraoxon in rat hippocampal slices. (2010)
  • Author(s): Narimatsu E, Niiya T, Kawamata T, Kawamata M, Yamakage M
  • Journal Title: Neurosci Res 68 Pages: 276-284
  • Peer Reviewed
• [Journal Article] Reduction of bone cancer pain by CB1 activation and TRPV1 inhibition (2010)
  • Author(s): Kawamata T
  • Journal Title: J Anesth Volume: 24 Pages: 328-332
  • NAID: 10027266825
  • Peer Reviewed
• [Journal Article] Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord (2010)
  • Author(s): Yanagisawa Y
  • Journal Title: Mol Pain Volume: 6 Pages: 6-6
  • Peer Reviewed
• [Journal Article] Molecular signaling of pruritus induced by endothelin-1 in mice (2010)
  • Author(s): Liang J
  • Journal Title: Exp Biol Med Volume: 235 Pages: 1300-1305
  • Peer Reviewed
• [Journal Article] Effects of atropine and pralidoxime on neuronal actions of paraoxon in rat hippocampal slices (2010)
  • Author(s): Narimatsu E
  • Journal Title: Neurosci Res Volume: 68 Pages: 276-284
  • Peer Reviewed
• [Journal Article] Involvement of TRPV1 in endothelin-l-induced pain-like behavior. (2009)
  • Author(s): Kawamata T, Wenjin J, Yamamoto J, Niiyama Y, Furuse S, Omote K, Namiki A.
  • Journal Title: Neuroreport 20 Pages: 233-237
  • Peer Reviewed
• [Journal Article] SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain. (2009)
  • Author(s): Niiyama Y, Kawamata T, Yamamoto J, Furuse S, Namiki A.
  • Journal Title: Brit J Anaesth 102 Pages: 251-258
  • Peer Reviewed
• [Journal Article] Reduction of bone cancer pain by activation of spinal cannabinoid receptor 1 and its expression in the superficial dorsal horn of the spinal cord in a murine model of bone cancer pain. (2009)
  • Author(s): Furuse S, Kawamata T, Yamamoto J, Niiyama Y, Omote K, Watanabe M, Namiki A.
  • Journal Title: Anesthesiology 111 Pages: 173-186
  • Peer Reviewed
• [Journal Article] Involvement of TRPV1 in endothelin-1-induced pain-like behavior (2009)
  • Author(s): Kawamata T, Wenjin J, Yamamoto J, Niiyama Y, Furuse S, Omote K, Namiki A.
  • Journal Title: Neuroreport 20 Pages: 233-237
• [Journal Article] SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain (2009)
  • Author(s): Niiyama Y, Kawamata T, Yamamoto J, Furuse S, Namiki A.
  • Journal Title: Brit J Anaesth 102 Pages: 251-258
• [Journal Article] Reduction of bone cancer pain by activation of spinal cannabinoid receptor 1 and its expression in the superficial dorsal horn of the spinal cord in a murine model of bone cancer pain (2009)
  • Author(s): Furuse S, Kawamata T, Yamamoto J, Niiyama Y, Omote K, Watanabe M, Namiki A.
  • Journal Title: Anesthesiology 111 Pages: 173-186
• [Journal Article] Reduction of bone cancer pain by activation of spinal cannabinoid receptor 1 and its expression in the superficial dorsal horn of the spinal cord in a murine model of bone cancer pain (2009)
  • Author(s): Furuse S
  • Journal Title: Anesthesiology 111 Pages: 173-186
  • Peer Reviewed
• [Journal Article] SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain (2009)
  • Author(s): Niiyama Y
  • Journal Title: Brit J Anaest 102 Pages: 251-258
  • Peer Reviewed
• [Journal Article] Involvement of TRPVl in endothelin-l-induced pain like-behavior (2009)
  • Author(s): Kawamata T
  • Journal Title: Nerureport 20 Pages: 233-237
  • Peer Reviewed
• [Journal Article] SB366791, a TRPVl antagonist, potentiates analgesic effects of systemic morphine on bone cancer pain (2009)
  • Author(s): Niiyama Y
  • Journal Title: Brit J Anaesth 102 Pages: 251-258
  • Peer Reviewed
• [Journal Article] Down-regulation of mu opioid receptor expression within distinct subpopulations of dorsal root ganglion neurons in a murine model of bone cancer pain. (2008)
  • Author(s): Yamamoto J, Kawamata T, Niiyama Y, Omote K, Namiki A.
  • Journal Title: Neuroscience 151 Pages: 843-853
  • Peer Reviewed
• [Journal Article] Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia. (2008)
  • Author(s): Kawamata T, Ji W, Yamamoto J, Niiyama Y, Furuse S, Namiki A.
  • Journal Title: Neuroscience 154 Pages: 1067-1076
  • Peer Reviewed
• [Journal Article] Expression of ASIC2 in ciliated cells and stereociliated cells. (2008)
  • Author(s): Kikuchi S, Ninomiya T, Kawamata T, Tatsumi H.
  • Journal Title: Cell Tissue Res 333 Pages: 217-224
  • Peer Reviewed
• [Journal Article] Down-regulation of mu opioid receptor expression within distinct subpopulations of dorsal root ganglion neurons in a murine model of bone cancer pain (2008)
  • Author(s): Yamamoto J, Kawamata T, Niiyama Y, Omote K, Namiki A.
  • Journal Title: Neuroscience 151 Pages: 843-53
• [Journal Article] Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia (2008)
  • Author(s): Kawamata T, Ji W, Yamamoto J, Niiyama Y, Furuse S, Namiki A.
  • Journal Title: Neuroscience 154 Pages: 1067-1076
• [Journal Article] Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-l-induced thermal hyperalgesia (2008)
  • Author(s): Kawamata T
  • Journal Title: Neuroscience 154 Pages: 1067-1076
  • Peer Reviewed
• [Journal Article] Down-regulation of mu opioid receptor expression within distinct subpopulations of dorsal root ganglion neurons in a murine model of bone cancer pain. Neuroscience 2008 ;151:5-72. (2008)
  • Author(s): Yamamoto Y
  • Journal Title: Neuroscience 151 Pages: 65-72
  • Peer Reviewed
• [Journal Article] 難治性癌性疼痛治療法開発に向けた研究 (2008)
  • Author(s): 川股知之
  • Journal Title: 麻酔 57 Pages: 39-50
• [Journal Article] Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons. (2007)
  • Author(s): Niiyama Y, Kawamata T, Yamamoto J, Omote K, Namiki A.
  • Journal Title: Neuroscience 148 Pages: 560-572
  • Peer Reviewed
• [Journal Article] Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons (2007)
  • Author(s): Niiyama Y
  • Journal Title: Neuroscience 148 Pages: 560-572
  • Peer Reviewed
• [Presentation] 骨がん疼痛を科学する (2010)
  • Author(s): 川股知之
  • Organizer: 第4回日本緩和医療薬学会年会
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-11-15
• [Presentation] 鎮痛補助薬 (2010)
  • Author(s): 川股知之
  • Organizer: 第48回日本癌治療学会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-30
• [Presentation] Gq-Coupled Receptors Sensitize TRPV1 through PLCB3 Activation in Peripheral Nociceptive Neurons (2010)
  • Author(s): Kawamata T
  • Organizer: Annual Meeting of American Society of Anesthesiologists
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-10-16
• [Presentation] Gq-Coupled Receptors Sensitize TRPV1 through PLC β3 Activation in Peripheral Nociceptive Neurons. (2010)
  • Author(s): Kawamata T, Tde S, Shimizu F, Fuseya S, Kawamata M
  • Organizer: Annual Meeting of American Society of Anesthesiologists
  • Place of Presentation: San Diego, USA
• [Presentation] Analgesic Tolerance by Repeated Activation of Spinal Cannabinoid Receptor 1 in Bone Cancer Pain. (2010)
  • Author(s): Kawamata T, Mochizuki N, Furuse S, Tanaka H, Kawamata M
  • Organizer: Annual Meeting of American Society of Anesthesiologists
  • Place of Presentation: San Diego, USA
• [Presentation] Spinal NMDA Receptor Is Involved in Bone Cancer-Induced Ongoing Pain but Not Movement-Evoked Pain. (2010)
  • Author(s): Kawamata T, Fuseya S, Furuse S, Yamamoto K, Kawamata M
  • Organizer: Annual Meeting of American Society of Anesthesiologists
  • Place of Presentation: San Diego, USA
• [Presentation] Enhancement of excitatory synaptic transmission in the substantia gelatinosa of the spinal cord in a mouse model of bone cancer pain. (2009)
  • Author(s): Yanagisawa Y, Furue H, Kawamata T, Uta D, Iwamoto Y, Imoto K, Yoshimura M.
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience.
  • Place of Presentation: Chicago, USA
• [Presentation] 骨がん疼痛 (2009)
  • Author(s): 川股知之
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: 神戸
• [Presentation] Effects of activation of spinal cannabinoid system on bone cancer pain. (2008)
  • Author(s): Furuse S, Kawamata T, Niiyama Y, Yamamoto J, Kiya T, Namiki A.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience.
  • Place of Presentation: Washington D.C., USA
• [Presentation] Change of TEEM8 expression in a rat model of paclitaxel-induced peripheral neuropathy. (2008)
  • Author(s): Kiya T, Ninomioya T, Kawamata T, Furuse S, Namiki A.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience.
  • Place of Presentation: Washington D.C., USA
• [Presentation] Analgesic effects of a novel TRPV1 antagonist and its interaction with morphine on bone cancer pain. (2008)
  • Author(s): Niiyama Y, Kawamata T, Niiyama Y, Furuse S, Namiki A.
  • Organizer: 12^<th> World Congress of Pain.
  • Place of Presentation: Glasgow, UK.
• [Presentation] Expression of phospholipase Cβ3 and β4 in the spinal cord. (2008)
  • Author(s): Kawamata T, Furuse S, Yamamoto J, Namiki A.
  • Organizer: 12^<th> World Congress of Pain.
  • Place of Presentation: Glasgow, UK.
• [Presentation] The behavioral and electrophysiological analysis of spinal nociceptive transmission in a murine model of bone cancer pain. (2008)
  • Author(s): Yanagisawa Y, Furue H, Kawamata T, Namiki A, Iwamoto Y, Yoshimura M.
  • Organizer: The 3rd Asian Pain Symposium.
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Analgesic effects of a novel TRPV1 antagonist and its interaction with morphine on bone cancer pain (2008)
  • Author(s): Niiyama Y, Kawamata T, Niiyama Y, Furuse S, Namiki A.
  • Organizer: 12^<th> World Congress of Pain
  • Place of Presentation: Glasgow, UK
• [Presentation] Expression of phospholipase Cβ3 and β4 in the spinal cord (2008)
  • Author(s): Kawamata T, Furuse S, Yamamoto J, Namiki A.
  • Organizer: 12^<th> World Congress of Pain
  • Place of Presentation: Glasgow, UK
• [Presentation] Effects of activation of spinal cannabinoid system on bone cancer pain (2008)
  • Author(s): Furuse S, Kawamata T, Niiyama Y, Yamamoto J, Kiya T, Namiki A.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., USA
• [Presentation] Change of TRPM8 expression in a rat model of paclitaxel-induced peripheral neuropathy (2008)
  • Author(s): Kiya T, Ninomioya T, Kawamata T, Furuse S, Namiki A.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., USA
• [Presentation] The behavioral and electrophysiological analysis of spinal nociceptive transmission in a murine model of bone cancer pain (2008)
  • Author(s): Yanagisawa Y, Furue H, Kawamata T, Namiki A, Iwamoto Y, Yoshimura M.
  • Organizer: The 3rd Asian Pain Symposium
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Analgesic effects of a novel TRPVl antagonist and its interaction with morphine on bone cancer pain (2008)
  • Author(s): Niiyama Y
  • Organizer: 12th World Congress of Pain
  • Place of Presentation: Glasgow, U. K.
• [Presentation] Expression of phospholipase Cβ3 and β4 in the spinal cord (2008)
  • Author(s): Kawamata T
  • Organizer: 12th World Congress of Pain
  • Place of Presentation: Glasgow, U. K.
• [Presentation] Effects of activation of spinal cannabinoid system on bone cancer pain (2008)
  • Author(s): Furuse S
  • Organizer: Society for Neuroscience 38th Annual Meeting
  • Place of Presentation: Washington D. C., U.S.A.
• [Presentation] Change of TRPM8 expression in a rat model of paclitaxel-induced peripheral neuropathy (2008)
  • Author(s): Kiya T
  • Organizer: Society for Neuroscience 38th Annual Meeting
  • Place of Presentation: Washington D. C., U.S.A.
• [Presentation] Analgesic effect of spinal CB1 activation on bone cancer pain and anal ysis of spinal CB1 expression (2007)
  • Author(s): Kawamata T
  • Organizer: Society for Neuroscience 37th Annual meeting
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-06
• [Presentation] Downregulation of mu opioid receptor and decreased analgesic effect of morphine on bone cancer pain. (2007)
  • Author(s): Yamamoto J, Kawamata T, Niiyama Y, Furuse S, Namiki A.
  • Organizer: Annual Meeting of American Society of Anesthesiologists.
• [Presentation] Analgesic effects of a novel TRPV1 antagonist and its interaction with morphine on bone cancer pain. (2007)
  • Author(s): Niiyama Y, Kawamata T, Furuse S, Yamamoto J, Namiki A.
  • Organizer: Annual Meeting of American Society of Anesthesiologists.
• [Presentation] Activation of spinal CB1 receptor reduces bone cancer pain. (2007)
  • Author(s): Furuse S, Kawamata T, Watanabe M, Niiyama Y, Yamamoto J, Namiki A.
  • Organizer: Annual Meeting of American Society of Anesthesiologists.
• [Presentation] Analgesic effect of spinal CB1 activation on bone cancer pain and analysis of spinal CB1 expression. (2007)
  • Author(s): Kawamata T, Watanabe M, Furuse S, Niiyama Y, Yamamoto J, Namiki A.
  • Organizer: Society for Neuroscience 37th Annual meeting
  • Place of Presentation: San Diego USA
• [Book] For Professional Anesthesiologists癌性痺痛(抗不整脈楽)(花岡一雄編) (2010)
  • Author(s): 川股知之
  • Publisher: 克誠堂出版
• [Book] がん看護別冊今日からできる緩和ケア(オピオイドローテーションとは)(小山冨美子, 山下めぐみ, 服部政治編) (2010)
  • Author(s): 高橋稔之, 川股知之
  • Publisher: 南江堂
• [Book] ペインクリニック別冊がんり冬痛管理に必要な知識(がん性痙痛)(小川節郎編) (2010)
  • Author(s): 川股知之
  • Publisher: 真興交易(株)医書出版部
• [Book] 慢性痙痛治療における有効な薬剤選定と治療薬開発のパラダイム(8節脊髄腔内i.t. PGF2投与モデル) (2010)
  • Author(s): 川股知之
  • Publisher: 技術情報協会
• [Book] 慢性癒痛治療における有効な薬剤選定と治療薬開発のパラダイム(9節腰部脊柱管狭窄モデル) (2010)
  • Author(s): 川股知之
  • Publisher: 技術情報協会
• [Book] 第1部術前.IX章中枢・末梢神経系(非ステロイド性抗炎症薬を長期に内服している.麻酔科トラブルシューティングA to Z.)(高崎真弓, 河本昌志, 川真田樹人, 岡本浩嗣編) (2010)
  • Author(s): 川股知之
  • Publisher: 文光堂
• [Book] 第1部術前.医章中枢・末梢神経系(長期にopioidを内服している.麻酔科トラブルシューティングA to Z.)(高崎真弓, 河本昌志, 川真田樹人, 岡本浩嗣編) (2010)
  • Author(s): 川股知之
  • Publisher: 文光堂
• [Book] For Professional Anesthesiologists癌性疼痛 (2010)
  • Author(s): 川股知之
  • Total Pages: 321
  • Publisher: 克誠堂出版
• [Book] がん疼痛管理に必要な知識 (2010)
  • Author(s): 川股知之
  • Total Pages: 239
  • Publisher: 真興交易(株)医書出版部
• [Book] 慢性疼痛治療における有効な薬剤選定と治療薬開発 (2010)
  • Author(s): 川股知之
  • Total Pages: 417
  • Publisher: 技術情報協会
• [Book] 麻酔科トラブルシューティングA to Z (2010)
  • Author(s): 川股知之
  • Total Pages: 637
  • Publisher: 文光堂
• [Book] 日常臨床に役立っ整形外科領域の痛みの知識(抗うっ薬)(山下敏彦編) (2009)
  • Author(s): 川股知之
  • Publisher: 金原出版株式会社
• [Book] 神経障害性癒痛の基礎と臨床I(慢性痺痛動物モデルの作り方) (2009)
  • Author(s): 川股知之, 表圭一, 並木昭義
• [Book] 神経障害性疼痛の基礎と臨床I(慢性疼痛動物モデルの作り方) (2009)
  • Author(s): 川股知之, 表圭一, 並木昭義
• [Book] 鎮痛補助薬(癒痛コントロールに用いられる薬,すぐに役立っがん患者の症状コントロールに用いられる薬の使い方と注意点)(並木昭義監.川股知之編) (2008)
  • Author(s): 川股知之
  • Publisher: 真興交易(株)医書出版部
• [Book] 硫酸モルヒネ細粒(モルペス(R)細粒)(オピオイド製剤の解説オピオイド研究と臨床応用の課題)(並木昭義編) (2008)
  • Author(s): 川股知之
  • Publisher: 真興交易(株)医書山版部
• [Book] オピオイド研究と臨床応用の課題(骨がん痙痛モデルにおけるMOR1発現とモルヒネ鎮痛効果)(並木昭義編) (2008)
  • Author(s): 山本純, 川股知之, 新山幸俊, 表圭一, 並木昭義
  • Publisher: 真興交易(株)医書出版部
• [Book] オピオイド研究と臨床応用の課題(並木昭義編, I. オピオイド製剤の解説3. 硫酸モルヒネ細粒 (モルペス【○!R】細粒)) (2008)
  • Author(s): 川股知之
  • Publisher: 真興交易(株)医書出版部
• [Book] オピオイド研究と臨床応用の課題(並木昭義編, 骨がん疼痛モデルにおけるMOR1発現とモルヒネ鎮痛効果) (2008)
  • Author(s): 山本純, 川股知之, 新山幸俊, 表圭一, 並木昭義
  • Publisher: 真興交易(株)医書出版部
• [Book] すぐに役立つ がん患者の症状コントロールに用いられる薬の使い方と注意点 (2008)
  • Author(s): 川股知之
  • Total Pages: 137
  • Publisher: 真興交易(株)医書出版部
• [Book] 癌痺痛治療のポイント(ペインクリニッシャンのための痛み診療のコツと落とし穴)(宮崎東洋編) (2007)
  • Author(s): 川股知之
  • Publisher: 中山書店