Spinal PKC activity and expression: role in tolerance produced by continuous spinal morphine infusion

V Granados-Soto, I Kalcheva, XY Hua, A Newton… - Pain, 2000 - Elsevier
It has been hypothesized that spinal morphine tolerance results from protein kinase C (PKC)
mediated phosphorylation. Chronic lumbar intrathecal (it) infusion of morphine (20
nmol/μl/h) was shown to produce antinociception on day 1 (d1) that disappeared by d5
(tolerance). On d6, a bolus it probe dose of morphine (60 nmol) produced a more profound
antinociception in saline-infused rats than in morphine-infused rats. Coinfusion of morphine
with a PKC inhibitor, chelerythrine, prevented tolerance to the probe morphine dose. Bolus it …