Involvement of neurotrophic factors in muscular pain and mechanisms for their production and action in the muscle

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390154
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pain science
• Research Institution: Chubu University
• Principal Investigator: MIZUMURA Kazue 中部大学, 生命健康科学部, 教授 (00109349)
• Co-Investigator(Kenkyū-buntansha): KATANOSAKA Kimiaki 名古屋大学, 環境医学研究所, 助教 (50335006) ; TAGUCHI Toru 名古屋大学, 環境医学研究所, 助教 (90464156)
• Co-Investigator(Renkei-kenkyūsha): MATSUDA Teru 中部大学, 生命健康科学部, 講師 (40367868)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 筋性疼痛 / 機械痛覚過敏 / 神経成長因子 / 筋細径線維受容器 / グリア細胞由来神経栄養因子 / 遅発性筋痛 / ATP / EP2受容体

Research Abstract

This study was planned to clarify involvement of neurotrophic factors in muscular pain models, their action mechanisms on muscular nociceptors, and factors that were involved in production of neurotrophic factors. Delayed onset muscle soreness (DOMS) induced after lengthening contraction (LC) was used for a model of muscle pain. We showed that EP2 receptor was involved in the COX-2-GDNF (glial cell derived neurotrophic factor) pathway leading to DOMS, and that upregulation of NGF and GDNF was induced in the muscle cells/satellite cells after LC. We also showed effects of NGF and GDNF on mechanically activated currents in cultured dorsal root ganglion neurons, sensitizing effect of GDNF on muscular A-delta mechano-sensitive nociceptors, and collaboration of NGF and GDNF in inducing muscular mechanical hyperalgesia.

Research Products

• [Journal Article] Glial cell line-derived neurotrophic factor sensitized the mechanical response of muscular thin-fiber afferents in rats (2014)
  • Author(s): Murase S, Kato K, Taguchi T, and Mizumura K
  • Journal Title: Eur.J.Pain Volume: 18 Pages: 629- 638
  • Peer Reviewed
• [Journal Article] Nociception originating from the crural fascia in rats (2013)
  • Author(s): Taguchi T, Yasui M, Kubo A, Abe M, Kiyama H, Yamanaka A, and Mizumura K
  • Journal Title: Pain Volume: 154 Pages: 1103-1114
  • Peer Reviewed
• [Journal Article] Decreased NGF upregulation is a mechanism for reduced mechanical hyperalgesia after the second bout of exercise in rats. Scan (2013)
  • Author(s): Urai H, Murase S, Mizumura K
  • Journal Title: J. Med. Sci. Sports
  • DOI: 10.1111/sms.12013
  • Peer Reviewed
• [Journal Article] TRPV1 and TRPV4 play pivotal roles in delayed onset muscle soreness (2013)
  • Author(s): Ota H, Katanosaka K, Murase S, Kashio M, Tominaga M, and Mizumura K
  • Journal Title: PLoS.ONE Volume: 8 Pages: e65751
  • Peer Reviewed
• [Journal Article] Upregulated glial cell line-derived neurotrophic factor through cyclo-oxygenase-2 activation in the muscle is requireed for mechanical hyperalgesia after exercise in rats (2013)
  • Author(s): Murase S, Terazawa E, Hirate K, Yamanaka H, Kanda H, Noguchi K, Ota H, Queme F, Taguchi T, and Mizumura K
  • Journal Title: J.Physiol Volume: 591 Pages: 3035-3048
  • Peer Reviewed
• [Journal Article] Repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia, facilitated temproral summation and expanded pain areas (2013)
  • Author(s): Hayashi K, Shiozawa S, Ozaki N, Mizumura K, and Graven-Nielsen T
  • Journal Title: Pain Volume: 154 Pages: 2344-2352
  • Peer Reviewed
• [Journal Article] Muscular heat and mechanical pain sensitivity after lengthening contraction in humans and animals (2013)
  • Author(s): Queme F, Taguchi T, Mizumura K, and Graven-Nielsen T
  • Journal Title: J.Pain Volume: 14 Pages: 1425-1436
  • Peer Reviewed
• [Journal Article] Absence of mechanical hyperalgesia after exercise (delayed onset muscle soreness) in neonatally capsaicin-treated rats (2012)
  • Author(s): Kubo A, Koyama M, Tamura R, Takagishi T, Murase S, and Mizumura K
  • Journal Title: Neurosci.Res Volume: 73 Pages: 56-60
  • Peer Reviewed
• [Journal Article] Involvement of NGF in the rat model of persistent muscle pain associated with taut band (2011)
  • Author(s): Hayashi Y, Ozaki N, Kawakita K, Itoh K, Mizumura K, Furukawa K, Yasui M, Hori K, Yi S-Q, Yamaguchi T, and Sugiura Y
  • Journal Title: J.Pain Volume: 12 Pages: 1059-1068
  • Peer Reviewed
• [Presentation] Contribution of TRPV1 and TRPV4 in Delayed Onset Muscle Soreness (2013)
  • Author(s): Ota H, Katanosaka K, Murase S, Kashio M, Tominaga M, Mizumura K
  • Organizer: 5th Asian Pain Symposium
  • Place of Presentation: 岡崎カンファレンスセンター(岡崎)
  • Year and Date: 20131218-20
• [Presentation] A synergetic effect of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in inducing muscular mechanical hyperalgesia in rats (2013)
  • Author(s): Murase S, Taguchi T, Queme F, Mizumura K
  • Organizer: 5th Asian Pain Symposium
  • Place of Presentation: 岡崎カンファレンスセンター(岡崎)
  • Year and Date: 20131218-20
• [Presentation] 遅発性筋痛におけるTRP チャネルV1, V4 の役割 (2013)
  • Author(s): 太田大樹, 片野坂公明, 村瀬詩織, 加塩麻紀子, 富永真琴, 水村和枝
  • Organizer: 第6回日本運動器疼痛学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2013-12-08
• [Presentation] 骨格筋細胞は持続する筋機械痛覚過敏を引き起こす神経成長因子(NGF)およびグリア細胞由来神経栄養因子(GDNF)を産生する (2013)
  • Author(s): 村瀬詩織, 山中博樹, 神田浩里, 水村和枝
  • Organizer: 第6回日本運動器疼痛学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2013-12-08
• [Presentation] 筋機械痛覚過敏を引き起こす神経成長因子(NGF)とグリア細胞由来神経栄養因子(GDNF)の相乗効果筋機械痛覚過敏を引き起こす神経成長因子(NGF)とグリア細胞由来神経栄養因子(GDNF)の相乗効果筋機械痛覚過敏を引き起こす神経成長因子(NGF)とグリア細胞由来神経栄養因子(GDNF)の相乗効果 (2013)
  • Author(s): 村瀬詩織, 水村和枝
  • Organizer: 第60回中部日本生理学会
  • Place of Presentation: 岐阜大学医学部記念会館ホール(岐阜)
  • Year and Date: 2013-10-25
• [Presentation] Muscular Nociceptor Heat Sensitivity in Rats After Lengthening Contraction and NGF (2013)
  • Author(s): Quemé F, Mizumura K
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀 (東京)
  • Year and Date: 2013-03-29
• [Presentation] 遅発性筋痛におけるシクロオキシゲナーゼCOX-2 とグリア由来神経栄養因子(GDNF)の役割 (2013)
  • Author(s): 水村和枝
  • Organizer: 第17回日本体力医学会東海地方会
  • Place of Presentation: 愛知学院大学楠本キャンパス歯学部基礎棟(名古屋)
  • Year and Date: 2013-03-16
• [Presentation] Glial cell-derived neurotrophic factor (GDNF) sensitized muscle Aδ-fiber afferents to mechanical stimulation and GDNF induced mechanical hyperalgesia was improved by intramuscular injection of amiloride in rats (2012)
  • Author(s): Murase S, Mizumura K
  • Organizer: 35th annual meeting of the Japan Neuroscience Society
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2012-09-19
• [Presentation] Involvement of TRPV1 and TRPA1 in the generation of mechanical hyperalgesia after exercise (delayed onset muscle soreness, DOMS) (2012)
  • Author(s): Ota H, Katanosaka K, Kashio M, Tominaga M, Mizumura K
  • Organizer: 35th annual meeting of the Japan Neuroscience Society
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2012-09-18
• [Presentation] 遅発性筋痛発生にEP2受容体が寄与する (2012)
  • Author(s): 太田大樹, 水村和枝
  • Organizer: 第34回日本疼痛学会
  • Place of Presentation: 熊本国際交流会館(熊本)
  • Year and Date: 2012-07-20
• [Presentation] COX-2, nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF), which play pivotal roles in delayed onset muscle soreness (DOMS), are produced by exercised skeletal muscle cells (2012)
  • Author(s): Murase S, Yamanaka H, Kanda H, Mizumura K
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野県松本文化会館(松本)
  • Year and Date: 2012-03-30
• [Presentation] グリア細胞由来神経栄養因子はラットの筋細径線維の機械応答性を増大する (2011)
  • Author(s): 村瀬詩織, 加藤健祐, 田口徹, 水村和枝
  • Organizer: 第58回中部日本生理学会
  • Place of Presentation: 福井県県民ホール(福井)
  • Year and Date: 20111101-02
• [Presentation] ラット神経損傷モデルにおける筋機械痛覚過敏と神経成長因子の関与の検討 (2011)
  • Author(s): 鈴木実佳子, 水村和枝, 村瀬詩織
  • Organizer: 第33回日本疼痛学会
  • Place of Presentation: 愛媛県県民文化会館(松山)
  • Year and Date: 20110722-23
• [Presentation] Effects of glial cell line-derived neurotrophic factor (GDNF) on the mechanical response of rat muscle thin-fiber receptors in vitro (2011)
  • Author(s): Mizumura K, Murase S, Taguchi T
  • Organizer: The 41st annual meeting of the Society for Neuroscience
  • Place of Presentation: コングレスセンター(Washington DC, U.S.A.)
  • Year and Date: 2011-11-13
• [Book] Analysis of nociceptors with muscle-and visceral-nerve preparations in vitro. In : Pain models - translational relevance and applications, eds H.O Handwerker, L.Arendt-Nielsen (2013)
  • Author(s): T.Taguchi, K.Mizumura
  • Total Pages: 47-60
  • Publisher: IASP press
• [Book] Neural mechanisms and devel-opmenttal process of mechanically induced pain -insights obtained from the study on the mechanical hyperalgesia after exercise (delay-ed onset muscle soreness)- in : Shi Yong-dechief editor. Recent Advances in Mechano-biology (2012)
  • Author(s): Katanosaka K, Murase S, Taguchi T, Mizumura K
  • Total Pages: 181-188
  • Publisher: Shanghai Scientific and Technological Literature Publishing House
• [Remarks] 中部大学大学理学療法学科水村研究室
  • URL: http://www.isc.chubu.ac.jp/myalgia/