FRONTIERS IN BIOSCIENCE;
SCIENCE NEWS DIGEST FOR PHYSICIANS AND SCIENTISTS
October 97



ROLE OF PKC g l IN NEUROPATHIC PAIN

Peripheral injury produces neuropathic pain which is characterized by invoking of pain by non-painful stimuli (allodynia) and exaggerated pain in response to painful stimuli (hyperalgesia). Neuropathic pain is difficult to manage. To some extent, the pain can be controlled by anti-inflammatory or opioid drugs. However, the neuropathic pain as a result of loss of a limb (phantom limb syndrome), reflex sympathetic dystrophy and post-herpetic neuralgia do not respond to these treatments.

The underlying basis of the neuropathic pain is not clear, but is thought to be related to the to N-methyl-D-asparate (NMDA) receptor mediated state of hyperexcitability. Therefore, the the post-receptor signal inducers that lie downstream from the receptor mediated responses may be involved in the persistence of the pain. Annika et al, in the October 10th issue of Science describe the involvement of the PKC g in such pain. The authors showed that in mice that lack PKC g, actue pain is preserved, yet the neuropathic pain is reduced . In addition, PKCg was shown to be confined to a small subset of dorsal horn neurons. These findings, provide the potential molecular pathway which is involved in the persistence of pain and which may be used as a target for its treatment.

Protein kinase C gamma isoform

Normal responses to flunitrazepam or pentobarbital
Reduction of immunoactivity in cerebellum to undetectable levels without alteration to levels of beta1, or beta2 isoforms
Reduction of sensitivity to effects of ethanol


Impaired elimination of multiple climbing fiber innervation of cerebellar

Harris, 1995
Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors
Proc Natl Acad Sci U S A 92, 3658-3662 (1995) [95249532]
Normal responses to acute pain stimuli
Fail to develop a neuropathic pain syndrome after partial sciatic nerve section
Blunting of the neurochemical changes occuring in the spinal cord after nerve injury
Annika B, 1997
Preserved acute pain and reduced neuropathic pain in mice lacking PKCg
Science 278, 279-283, 1997

METHODOLOGY ( FROM T-BASE)

( (pkc-gamma))

Line Name DNA Construct
1. PKC-gamma (+/-) Calcium-phospholipid-dependent protein kinase subtype gamma was cloned from a 129/Ola mouse genomic cosmid library with a rat PKC-gamma cDNA probe. The exon structure w....
2. PCK-gamma (+/-) & l Calcium-phospholipid-dependent protein kinase subtype gamma was cloned from a 129/Ola mouse genomic cosmid library with a rat PKC-gamma cDNA probe. The exon structure w....
3. PKC-gamma (-/-) Calcium-phospholipid-dependent protein kinase subtype gamma was cloned from a 129/Ola mouse genomic cosmid library with a rat PKC-gamma cDNA probe. The exon structure w....
4. PKC-gamma (-/-) (et Calcium-phospholipid-dependent protein kinase subtype gamma was cloned from a 129/Ola mouse genomic cosmid library with a rat PKC-gamma cDNA probe. The exon structure w....
5. PCK-gamma (-/-) & l Calcium-phospholipid-dependent protein kinase subtype gamma was cloned from a 129/Ola mouse genomic cosmid library with a rat PKC-gamma cDNA probe. The exon structure w....


Database Links

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