| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
The aim of this study was to explore (1) whether renin-angiotensin axis associates with neuropathic pain and (2) the efficacy of antisense therapy on treatment of neuropathic pain.
1) Clinical study :
ACE gene polymorphism (DD and II homozygotes, and ID heterozygotes) associates the genetic risk factor for neuropathic pain. The distribution of the DD, ID and II genotypes in the study group is 33%, 33% and 33%, respectively. ACE activity was significantly higher in subjects with the ACE DD genotype than subjects with the ID and II genotypes. No significant difference in heart rate and blood pressure variabilities, plasma renin activity, angiotensin I and II was detected among the ACE genotypes. The frequency of the ACE DD genotype in the present population (33%) was higher than those previously described in other normal populations of the same race (20%)
In addition, the frequency of the ACE DD genotype in CRPS type I was higher than those in CRPF type II.
It is possible that the DD genotyp
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e favors the development of neuropathic pain as well as cardiovascular disease, perhaps through the presence of higher ACE concentrations. Elevated ACE activity in these subjects may result in increased angiotensin II levels in the effector site, and this might be a mechanism underlying the association between the ACE deletion polymorphism and the increased genetic risk for susceptibility to neuropathic pain.
2) Basic study :
We investigated the effects of intrathecal infusion of naloxone on mechanical hypersensitivity and the relationship between high blood pressure and the analgesia in SHR. Measurements were performed before and 15min after the intrathecal administration of naloxone. There was no significant differences in systolic blood pressure after the intrathecal infusion of naloxone. This finding might indicate that naloxone had blocked both μ-receptor which had a hypertensive action and κ-receptor which had a hypotensive action.
Anti-sense gene therapy for angiotensin II type 1 in SHR showed decreased blood pressure by 30mmHg and unchanged mechanical allodynia, suggesting that central rennin-angiotensin axis showed to decrease nociception, while peripheral rennin-angiotensin axis increased nocecption.
In conclusion, renin-angiotensin system may play dual effects on mononeuropathic pain : relieved heat allodynia due to central opioid system, and aggravation of peripheral mononeuropathy arising from renin-angiotensin induced vasospastic phenomenon. Further investigation may be needed concerning the genetic predisposition for mononeuropathic pain in relation to hypertension. Less
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