Development of analgesic strategy with anti-tumor effect

• Project/Area Number: 17H04322
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Wakayama Medical University
• Principal Investigator: Kawamata Tomoyuki 和歌山県立医科大学, 医学部, 教授 (80336388)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: がん疼痛 / 局所麻酔薬 / 電化 / QX-314 / がん性痛 / がん増殖 / TRPA1 / TRPV1 / がん / 痛み / 受容体 / 脳神経

Outline of Final Research Achievements

Our previous study has showed that TRPV1-positive afferents are involved in both cancer growth and cancer-induced pain. QX-314, a quaternary lidocaine derivative, has a permanent positive charge that theoretically impairs its ability to cross neuronal membranes. However, When TRPV1 was activated, extracellular QX-314 could produce a local anesthetic effect through entering the pore of TRPV1. Our results of this study revealed that systemic QX-314 decreases both cancer pain and cancer growth due to inhibition of activated TRPV1-positive afferents.

Academic Significance and Societal Importance of the Research Achievements

これまで、鎮痛治療と抗がん治療は別に考えられてきた。したがって、痛み神経とがんの生育を結びつけた本研究は学術的な意義は非常に大きい。本研究は、正に電化した局所麻酔薬QX-314を使用して、痛みと軸索反射をブロックする。痛みの伝達と腫瘍増殖に関与している活性化TRPV1(+)神経のみを選択的に抑制でき、活性化していないTRPV1(+)神経やTRPV1(-)神経、および中枢神経には作用しないことから、副作用が非常に少ない治療が期待できる。したがって、本研究結果が臨床応用されることにより副作用の少ない痛み治療・がん治療が可能となることが予想され、その臨床的意義は大きい。

Research Products

• [Journal Article] Validation of noninvasive continuous arterial pressure measurement by ClearSight System during induction of anesthesia for cardiovascular surgery (2020)
  • Author(s): Tanioku Tadashi、Yoshida Akari、Aratani Yuichi、Fujii Keisuke、Kawamata Tomoyuki
  • Journal Title: BMC Anesthesiology Volume: 20 Issue: 1 Pages: 176-183
  • DOI: 10.1186/s12871-020-01091-x
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase Cβ3 Expressed in Mouse DRGs is Involved in Inflammatory and Postoperative Pain (2020)
  • Author(s): Ide Susumu、Kawamata Tomoyuki、Ishida Kumiko、Fuseya Satoshi、Ishida Takashi、Sugiyama Yuki、Kawamata Mikito、Tanaka Satoshi
  • Journal Title: Journal of Pain Research Volume: Volume 13 Pages: 3371-3384
  • DOI: 10.2147/jpr.s280565
  • Peer Reviewed / Open Access
• [Journal Article] Opioid free anesthesia/analgesia (2020)
  • Author(s): 川股知之、小川舜也
  • Journal Title: 臨床麻酔 Volume: 44 Pages: 1542-1549
  • Peer Reviewed
• [Journal Article] 手術麻酔中の疼痛評価 (2020)
  • Author(s): 川股知之、若林美帆
  • Journal Title: ペインクリニック Volume: 41 Pages: 22-30
  • Peer Reviewed
• [Journal Article] Transcriptionalnfactor Sp4 is required for hyperalgesic state persistence (2019)
  • Author(s): Sheehan K, Kawamata T, et al
  • Journal Title: PLOS One Volume: 14
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Optimal Timing of Removal of Epidural and Urethral Catheters to Avoid Postoperative Urinary Retention Undergoing Abdominal Surgery. (2019)
  • Author(s): Hayami S, Ueno M, Kawai M, Kuriyama T, Kawamata T, Yamaue H.
  • Journal Title: Dig Surg. Volume: 36 Issue: 3 Pages: 261-265
  • DOI: 10.1159/000490199
  • Peer Reviewed
• [Journal Article] Comparison of catheter-over-needle and catheter-through-needle on leakage from the catheter insertion site during continuous femoral nerve block. (2018)
  • Author(s): Nogawa R, Maruyama T, Kimoto Y, Yamazaki A, Kawamata T
  • Journal Title: J Anesth Volume: 32 Issue: 3 Pages: 439-442
  • DOI: 10.1007/s00540-018-2479-7
  • Peer Reviewed
• [Journal Article] Perinatal outcome of vaginal delivery with epidural analgesia initiated at the early or late phase of labor period: A retrospective cohort study in the Japanese population (2018)
  • Author(s): Michihisa Shiro, Katsutoshi Nakahata, Sawako Minami, Tomoyuki Kawamata, Kazuhiko Ino
  • Journal Title: The Journal of Obstetrics and Gynaecology Research Volume: in press Issue: 8 Pages: 1415-1423
  • DOI: 10.1111/jog.13671
  • Peer Reviewed
• [Journal Article] Effects of perinatal blood pressure on maternal brain functional connectivity (2018)
  • Author(s): Kurosaki Hiromichi、Nakahata Katsutoshi、Donishi Tomohiro、Shiro Michihisa、Ino Kazuhiko、Terada Masaki、Kawamata Tomoyuki、Kaneoke Yoshiki
  • Journal Title: PLOS ONE Volume: 13 Issue: 8 Pages: e0203067-e0203067
  • DOI: 10.1371/journal.pone.0203067
  • Peer Reviewed / Open Access
• [Journal Article] Detection of Acute Arterial Occlusion During Artery Bypass Surgery for a Lower Extremity by Monitoring Regional Saturation of Oxygen of the Sole of the Foot (2017)
  • Author(s): Kurosaki H, Higuchi M, Nogawa R, Kawamata T
  • Journal Title: J Cardiothorac Vasc Anesth Volume: 6 Issue: 6 Pages: 2167-9
  • DOI: 10.1053/j.jvca.2017.03.003
  • Peer Reviewed
• [Journal Article] 腹部大動脈瘤ステントグラフト内挿術に対する末梢神経ブロックによる麻酔管理 (2017)
  • Author(s): 2.正木美帆、山﨑亮典、大森亜紀、川股知之
  • Journal Title: 麻酔 Volume: 66 Pages: 761-764
  • NAID: 40021257708
  • Peer Reviewed
• [Presentation] Long-term observation of changes in functional connectivity in patients with postherpetic neuralgia (2020)
  • Author(s): Kurosaki H, Hirai A, Ogawa S, Yamasaki K, Kawamata T
  • Organizer: Annual Meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] Does temperature measured by Temple Touch Pro TM over the radial artery reflector temperature? (2020)
  • Author(s): Nishibata M, Yoshida A, Maruyama T, Kobai K, Kawamata T
  • Organizer: Annual Meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] Validation of estimated continuous cardiac output in patients undergoing laparoscopic surgery. (2020)
  • Author(s): Maruyama T, Tanioku T, Aratani Y, Kanda Y, Kawamata T
  • Organizer: Annual Meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] A case in which ultrasound was useful for repeated evaluation of pneumothorax during laparoscopic surgery (2019)
  • Author(s): Ogawa S, Tsujimoto M, Kawmata T
  • Organizer: Annual meeting of the American society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] TRPV1 is involved in both tumor growth and cancer-induced pain (2019)
  • Author(s): Yoshida Q, Tanioku T, Aratani Y, Maruyama T, Tsujimoto M,vbKawamat T
  • Organizer: Annual meeting of the American society of Anesthesiologists
• [Presentation] NSAIDs (2018)
  • Author(s): 川股知之
  • Organizer: 日本麻酔科学会第65回大会
  • Invited
• [Presentation] 統合型臨床情報システムDWHが切り開く周術期データ検索とその可能性 (2018)
  • Author(s): 川股知之
  • Organizer: 日本麻酔科学会第65回大会
  • Invited
• [Presentation] Altered spontaneous brain activity in chronic PHN patients (2018)
  • Author(s): Kurosaki H, Tazoe M, Ogawa S, Kawamata T
  • Organizer: Annual meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] TRPA1 is involved in cancer-induced spontaneous pain but not mechanical and thermal hyperalgesia (2018)
  • Author(s): Yoshida A, Ogawa S, Tazoe M, Kawamata T
  • Organizer: Annual meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] Altered resting-state functional connectivity of pain-related brain regions in patients with postherpetic neuralgia (2017)
  • Author(s): Kurosaki H, Kan S, Nakata R, Yamazaki A, Kuriyama T, Mizumoto K, Shibata M, Kawamata T
  • Organizer: Annual Meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] Validation of ClearSight System during anesthetic induction in patients undergoing cardiovascular surgery (2017)
  • Author(s): Tanioku T, Higashi S, Deguchi K, Boki K, Nishibata M, Kawamata T
  • Organizer: Annual Meeting of the American Society of Anesthesiologists
  • Int'l Joint Research
• [Presentation] Current status and future development of cancer pain management (2017)
  • Author(s): Kawamata T
  • Organizer: 25th Chinese Society of Anesthesiologists
  • Int'l Joint Research / Invited
• [Book] LiSA別冊秋号 頭痛と鎮痛 (2018)
  • Author(s): 川股知之
  • Total Pages: 187
  • Publisher: メディカル・サイエンス・インターナショナル
• [Book] 麻酔科研修ノート改訂第三版 (2018)
  • Author(s): 吉田朱里、川股知之
  • Total Pages: 764
  • Publisher: 診断と治療社
  • ISBN: 9784787824011
• [Book] 日めくり麻酔科エビデンスアップデート２ (2018)
  • Author(s): 吉田朱里、川股知之
  • Total Pages: 239
  • Publisher: 克誠堂
  • ISBN: 9784771905085