RESUMO
One possible mechanism to account for the pain enhancing effects of protein kinase C (PKC) activation may be a facilitation of neurotransmitter release from terminals of nociceptive sensory neurons in the spinal cord. To examine this notion, we studied whether treatment with a phorbol ester enhanced the resting and capsaicin-evoked release of immunoreactive substance P (iSP) and immunoreactive calcitonin gene-related peptide (iCGRP) using an in vitro spinal cord slice preparation. Exposing the spinal cord tissue to 100 nM phorbol 12,13 dibutyrate (PDBu), an activator of PKC, results in a two-fold increase in the basal and the capsaicin-evoked release of iSP and iCGRF compared to evoked peptide release without PDBu. When the tissue was perfused with 1 microM 4-alpha PDBu, an analog of PDBu that does not activate PKC, the peptide release was not significantly different from control. Pre-exposing slices to 1 microM bisindolylmaleimide I, an inhibitor of PKC activity, prevents the facilitation of peptide release induced by PDBu. These results suggest that activation of PKC can augment the release of peptides in the spinal cord, which could increase nociceptive sensory transmission and contribute to hyperalgesia.
