Regenerations of Spinal Cord Neurons and its Sensory Function in Pathological Pain following Peripheral Nerve Injury
| Project/Area Number |
13470321
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | YAMAGUCHI UNIVERSITY |
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Principal Investigator |
ISHIKAWA Toshizo YAMAGUCHI UNIV. SCH. MEDICINE PROFESSOR, 医学部, 教授 (90034991)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAHARA Masato YAMAGUCHI UNIV. SCH. MEDICINE PROFESSOR, 医学部, 教授 (20136188)
IBUKI Takae KYOTO PREF. UNIV. SCH. MEDICINE ASSOC. PROFESSOR, 医学部, 講師 (90232587)
FURUKAWA Shoei GIFU PHARMAC. COLL. PROFESSOR, 薬学部, 教授 (90159129)
MATSUI Tomohiro YAMAGUCHI UNIV. SCH. MEDICINE ASSOC. PROFESSOR, 医学部, 助手 (50314828)
OKANO Kozue YAMAGUCHI UNIV. SCH. MEDICINE ASSOC. PROFESSOR, 医学部, 講師 (50160693)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | NEUROPATHIC PAIN / NEURONAL PLASTICITY / SPINAL GLUTAMATE / C-FOS EXPRESSION / APOPTOSIS / CA ENTRY BLOCKER / NERVE GROWTH FACTOR / 痛み / 脊髄細胞 / グルタメート神経 |
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| Research Abstract |
The neuronal plasticity of the spinal cord sensory system in pathological pain after peripheral nerve injury has recently recognized as pivotal mechanisms. However, there are no report concerning with combined mechanisms such as regeneration of cellular and functional derangements. The aim of the present study was to investigate the possibility of regeneration of spinal cord neurons of pathological pain using well-established rat model, which is known that the excessive release of glutamate and sP initiate perturbation of intracellular-nucleus processing resulting in increased Ca2+ In addition, we investigated possibilities for treatment resulting from these mechanisms including suppression of afferent input and synthesis of nerve growth factor by magnetic field stimulation. In Rats, the neuropathic pain was produced by legation of left sciatic nerve. Under halothane anesthesia special designed micro dialysis catheter was intrathecally implanted along with PE-10 tube for the spinal glu
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tamate release (HPLC-UV) and drug injection, respectively. For the treatment (1) several kinds of N-type Ca channel blocker (IT), (2) magnetic field stimulation (MFS), or (3) MFS + anti NGF (4) MFS + 4-methyl catechol (4-MC, IP) was respectively administered. After nerve injury, rats showed thermal hyperalgesia accompanied with increased spinal glutamate release during 5-10 days and that was enhanced with time. There were c-foes protein expression and apoptosis of superficial layer of spinal cord during early state of the hyperalgesia followed by the necrosis of the laminate 3-4 (interneuron). Both N-type Ca channel blocker and MFS significantly attenuated spinal glutamate release accompanied with decreased incidences of c-foes, apoptosis and necrosis of spinal cord neurons. In addition, pretreatment of anti NGF with MFS showed less sever of pain facilitation and 4-MC administration, which brings about the synthesis induction of the NGF that it attenuates the spinal glutamate release, and intracellular signaling including c-foes and that, suppresses these histological changes. Based on this study, it is suggested that possible involvement of peripheral nerve growth factors induced by magnetic field stimulation in regeneration of spinal cord neurons and related to attenuation of sensory systems such that of pathological pain. We also reconfirmed that generates modulation in the intracellular - nucleus process, which originates from the excessive excitation of the spinal cord glutamate nerve system and brings about the apoptosis. For the conversion to chronic pain, it was indicated that the dysfunction of the interneuron was concerned, and promotes further understand mechanisms of the nerve - immune network. It proves application of these treatments to the functional recovery in the clinical situation that the induction of the nerve growth factor restores the process for cell death in addition to the usefulness of N-type Ca channel blocker and magnetic field stimulation. As future direction, it will be needed to establish the transplantation and adeno-vector virus NGF administration for possible treatment for neuropathic pain. Less
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Report
(3 results)
Research Products
(41 results)
