Hyperalgesia following unilateral complete
Freund's adjuvant-induced
inflammation was characterized by paw withdrawal latency to thermal stimulus. Paw withdrawal latencies were significantly shorter on the complete
Freund's adjuvant-treated paw than on the contralateral paw of the complete
Freund's adjuvant- and the
sham-treated rats. Total cytosolic
protein kinase C activity in the lumbar enlargement was unchanged on the sides of the spinal cord ipsi- and contra-lateral to the inflamed paw. Membrane-associated activities of
protein kinase Calpha,
protein kinase CbetaI and
protein kinase Cgamma did not change significantly on the sides of the cord ipsi- and contra-lateral to the
inflammation. However, membrane-associated activity of
protein kinase CbetaII was increased in the cord section ipsilateral to the
inflammation, suggesting that increased translocation/activation of
protein kinase CbetaII is related to
thermal hyperalgesia.
Dextrorphan (an
N-methyl-D-aspartate receptor antagonist), L-703,606 (an
NK-1 receptor antagonist) and an antisense
oligodeoxynucleotide for a selective knockdown of
protein kinase Cbeta, reduced complete
Freund's adjuvant-induced
hyperalgesia, and reversed significant changes in the membrane activity of
protein kinase CbetaII on the spinal cord section ipsilateral to the inflamed paw.
Dextrorphan and
protein kinase Cbeta antisense
oligodeoxynucleotide were effective in reversing complete
Freund's adjuvant-induced increase in the activity of
protein kinase CbetaII ipsilateral to the
inflammation at all the doses tested, but L-703,606 was effective only at the highest dose. Furthermore, in the presence of inflammatory stimulus,
dextrorphan and L-703,606 did not alter the activities of
membrane-associated protein kinase Calpha,
protein kinase CbetaI, and
protein kinase Cgamma in the section of the spinal cord ipsi- and contra-lateral to the
inflammation.
Protein kinase Cbeta antisense
oligodeoxynucleotide had no significant effect on the membrane-associated activities of
protein kinase Calpha and
protein kinase Cgamma, but decreased the activities of both
protein kinase CbetaI and
protein kinase CbetaII and the expression of
protein kinase Cbeta
isozyme in the spinal cord. The data provide evidence that a common molecular event that converges to initiate and maintain
hyperalgesia may include the translocation and activation of
protein kinase CbetaII in the spinal dorsal horn.