2006 Fiscal Year Final Research Report Summary
Implication of brain and spinal protein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain
| Project/Area Number |
16591530
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of Toyama (2005-2006)
Toyama Medical and Pharmaceutical University (2004) |
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Principal Investigator |
YAMAZAKI Mitsuaki University of Toyama, Anesthesiology, Professor, 医学部, 教授 (70158145)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Rika University of Toyama, Anesthesiology, Instructor, 医学部, 助手 (10345572)
NARITA Minoru Hoshi University, Pharmaceutical Science, Associate Professor, 薬学部, 助教授 (40318613)
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| Project Period (FY) |
2004 – 2006
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| Keywords | chronic pain / nerve injury / neuropathic pain / anxiety / opioid / amygdala / light-dark test / morphine dependence |
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| Research Abstract |
The object of this project is to elucidate the mechanism of neuropathic pain mainly by the action of PKC in the brain and spinal cord, and apply some drugs to chronic pain treatment.
1) Activated PKC in the spinal cord with chronic pain-like hyperalgesia may play a substantial role in the suppression of the morphine-induced rewarding effect with pain-like hyperalgesia. 2) Activation of PKCs (cPKC, PKC ζ) within the spinal cord is directly rewarding effect under a neuropathic pain-like state. 3) The stimulation of spinal PKC results in an enhancement of neuronal activity in the parafascicular nuclei, amygdala and cingulate cortex associated with hyperalgesia. 4) The phosphorylation of the μ-opioid receptor in the spinal cord under a neuropathic pain-like state may contribute to the reduction of in the antinociceptive effect produced by morphine. 5) The mice showed significant anxiety-related behavior with dramatic down-regulations of δ-opioidergic and serotonergic function. 6) Repeated administrations of low-dose antidepressants, imipramine, milnacipran, paroxetine, significantly prevented the anxiety-related behaviors induced by chronic neuropathic pain.
Serotonergic antidepressants are effective for treating anxiety associated with chronic neuropathic pain and useful for treating neuropathic pain with emotional dysfunction. Furthermore, the mechanism of these serotonergic antidepressants may be associated with a down-regulation of serotonergic function in prefrontal cortex and amygdala.
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