Critical role for spinal caspase-1 in neuropathic pain development through its distinct regulation of cytokines

• Project/Area Number: 22790195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Hyogo Medical University
• Principal Investigator: MIYOSHI Kan 兵庫医科大学, 医学部, 助教 (30454755)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Caspase-1 / IL-18 / microglia / neuropathic pain / spinal cord / astrocytes / glial interaction / caspase-1 / astrocyte / TLR4 / IL-1β

Research Abstract

SNL induced an increase in the expression of IL-18 and caspase-1 in microglia, in the spinal dorsal horn. Intrathecal injection of the TLR4 agonist, LPS, produced upregulation of Iba1, caspase-1, and IL-18 expression, which was prevented by a p38 MAPK inhibitor. Both anti-IL-18 antibody and caspase-1 inhibitors alleviated SNL-induced tactile allodynia. Conversely, intrathecal injection of IL-18 produced both tactile allodynia. IL-18-deficient mice or caspase-1-deficient mice did not develop tactile allodynia after SNL. Thus, blocking IL-18 signaling in glial cells might provide a fruitful strategy for treating neuropathic pain.

Research Products

• [Journal Article] Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation (2012)
  • Author(s): Fukuoka T, Yamanaka H, Kobayashi K, Okubo M, Miyoshi K, Dai Y, Noguchi K
  • Journal Title: Pain Volume: 153 Issue: 1 Pages: 68-79
  • DOI: 10.1016/j.pain.2011.09.009
  • Peer Reviewed
• [Journal Article] Spinal 5-HT(3) receptor activation induces behavioral hypersensitivity via a neuronal-glial-neuronal signaling cascade (2011)
  • Author(s): Gu M, Miyoshi K, Dubner R, Guo W, Zou S, Ren K, Noguchi K, Wei F.
  • Journal Title: J. Neurosci. Volume: 31 Issue: 36 Pages: 12823-12836
  • DOI: 10.1523/jneurosci.1564-11.2011
  • Peer Reviewed
• [Journal Article] Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex (2011)
  • Author(s): Narita M, Niikura K, Nanjo-Niikura K, Narita M, Furuya M, Yamashita A, Saeki M, Matsushima Y, Imai S, Shimizu T, Asato M, Kuzumaki N, Okutsu D, Miyoshi K, Suzuki M, Tsukiyama Y, Konno M, Yomiya K, Matoba M, Suzuki T.
  • Journal Title: Pain Volume: 152 Issue: 6 Pages: 1358-1372
  • DOI: 10.1016/j.pain.2011.02.016
  • Peer Reviewed
• [Journal Article] Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex (2011)
  • Author(s): Narita, M., et.al.
  • Journal Title: Pain Volume: (in press)
  • Peer Reviewed
• [Presentation] Critical role for spinal IL-18/caspase-1 interaction in neuropathic pain development through its distinct regulation of interleukins (2010)
  • Author(s): Miyoshi K, Noguchi K.
  • Organizer: World Congress on PAIN
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2010-08-30
• [Presentation] Critical role for spinal IL-18/caspase-1 interaction in neuropathic pain development through its distinct regulation of interleukins. (2010)
  • Author(s): Miyoshi, K., et.al.
  • Organizer: 13th World Congress on Pain (IASP)
  • Place of Presentation: Canada (montreal)
  • Year and Date: 2010-08-30