Molecular biological study of novel gene therapy for pain that is difficult to treatment.

• Project/Area Number: 16K20077
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Asahikawa Medical College
• Principal Investigator: KANDA Megumi 旭川医科大学, 医学部, 助教 (50516820)
• Research Collaborator: KANDA Hirotsugu 旭川医科大学, 医学部, 講師 (00550641) ; IIDA Takafumi 旭川医科大学, 医学部, 助教 (40468442) ; HAO Shuanglin University of Miami, Preclinical and Basic Research Department of Anesthesiology, Professor and Director
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝子治療 / ウイルスベクター / 神経障害性疼痛 / 妊娠による鎮痛効果 / 難治性疼痛 / アンチセンス法 / 活性酸素 / ミトコンドリア

Outline of Final Research Achievements

While effective antiretroviral treatment makes human immunodeficiency virus (HIV)-related death decreased dramatically, neuropathic pain becomes one of the most common complications in patients with HIV/acquired immunodeficiency syndrome (AIDS). The exact mechanisms of HIV-related neuropathic pain are not well understood yet, and no effective therapy is for HIV-pain. Evidence has shown that proinflammatory factors (e.g., tumor necrosis factor alpha (TNFα)) released from glia, are critical to contributing to chronic pain. Preclinical studies have demonstrated that non-replicating herpes simplex virus (HSV)-based vector expressing human enkephalin reduces inflammatory pain, neuropathic pain, or cancer pain in animal models. In this study, we describe recent advances in the use of HSV-based gene transfer for the treatment of HIV pain, with a special focus on the use of HSV-mediated soluble TNF receptor I (neutralizing TNFα in function) in HIV neuropathic pain model.

Research Products

• [Journal Article] Pregnancy suppresses neuropathic pain induced by chronic constriction injury in rats through the inhibition of TNF-α. (2017)
  • Author(s): Onodera Y, Kanao-Kanda M, Kanda H, Sasakawa T, Iwasaki H, Kunisawa T.
  • Journal Title: J Pain Res Volume: 10 Pages: 567-574
  • DOI: 10.2147/jpr.s121810
  • NAID: 120006401530
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gene therapy with HSV encoding p55TNFR gene for HIV neuropathic pain: an evidence-based mini-review. (2017)
  • Author(s): Kanda H, Liu S, Kanao M, Yi H, Iida T, Huang W, Kunisawa T, Lubarsky DA, Hao S.
  • Journal Title: Transl Perioper Pain Med. Volume: 2(4) Pages: 24-32
  • Peer Reviewed / Open Access
• [Presentation] Pregnancy Attenuates the Expression of TLR4 and Drp1 in the Spinal Cord of Rats With Neuropathic Pain (2017)
  • Author(s): Chinami Takahashi, Megumi Kanao-Kanda, Hirotsugu Kanda, Yoshiko Onodera, Izumi Sato, Takafumi Iida, Hiroshi Iwasaki, Takayuki Kunisawa.
  • Organizer: American Society of Anesthesiologists Annual Meeting Anesthesiology 2017
  • Int'l Joint Research
• [Presentation] Pregnancy suppresses mechanical allodynia by reversing the loss of GAD67 in the spinal dorsal horn in the chronic constriction injury rat model (2017)
  • Author(s): Megumi Kanao-Kanda, Izumi Sato, Yoshiko Onodera, Hirotsugu Kanda, Takafumi Iida, Hiroshi Iwasaki, Takayuki Kunisawa.
  • Organizer: American Society of Anesthesiologists Annual Meeting Anesthesiology 2017
  • Int'l Joint Research
• [Presentation] Pregnancy suppresses mechanical allodynia by reducing GFAP in the spinal dorsal horn in the chronic constriction injury rat model (2016)
  • Author(s): Yoshiko Onodera
  • Organizer: The Anesthesiology 2016 Annural Meeting
  • Place of Presentation: Chicago
  • Year and Date: 2016-10-23
  • Int'l Joint Research