Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2006-04-18
2006-04-18
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S816000, C514S817000, C514S818000, C514S922000
Reexamination Certificate
active
07030100
ABSTRACT:
Several lines of evidence have shown a role for the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the development of spinal hyperalgesia. However, the roles of effectors for cGMP are not fully understood in the processing of pain in the spinal cord. cGMP-dependent protein kinase (PKG) Iα but not PKGIβ was localized in the neuronal bodies and processes, and was distributed primarily in the superficial laminae of the spinal cord. Intrathecal administration of an inhibitor of PKGIα, Rp-8-[(4-Chlorophenyl)thio]-cGMPS triethylamine, produces significant antinociception. Moreover, PKGIα protein expression was dramatically increased in the lumbar spinal cord after noxious stimulation. This upregulation of PKGIα expression was completely blocked not only by a neuronal NO synthase inhibitor, and a soluble guanylate cyclase inhibitor, but also by an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. Noxious stimulation not only initially activates but also later upregulates PKGIα expression in the superficial laminae via an NMDA-NO-cGMP signaling pathway, suggesting that PKGIα plays an important role in the central mechanism of inflammatory hyperalgesia in the spinal cord.
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Johns Roger A.
Tao Yuanxiang
Banner & Witcoff LLP
Johns Hopkins University
Krass Frederick
LandOfFree
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