RT Journal Article
SR Electronic
T1 Sustained Morphine Treatment Augments Capsaicin-Evoked Calcitonin Gene-Related Peptide Release from Primary Sensory Neurons in a Protein Kinase A- and Raf-1-Dependent Manner
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 810
OP 817
DO 10.1124/jpet.109.151704
VO 330
IS 3
A1 Suneeta Tumati
A1 Henry I. Yamamura
A1 Todd W. Vanderah
A1 William R. Roeske
A1 Eva V. Varga
YR 2009
UL http://jpet.aspetjournals.org/content/330/3/810.abstract
AB Studies have shown that long-term (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol (morphine) treatment increases the sensitivity to painful heat stimuli (thermal hyperalgesia). The cellular adaptations contributing to sustained morphine-mediated pain sensitization are not fully understood. It was shown previously (J Neurosci 22:6747–6755, 2002) that sustained morphine exposure augments pain neurotransmitter [such as calcitonin gene-related peptide (CGRP)] release in the dorsal horn of the spinal cord in response to the heat-sensing transient receptor potential vanilloid 1 receptor agonist 8-methyl-N-vanillyl-6-nonenamide (capsaicin). In the present study, we demonstrate that sustained morphine-mediated augmentation of CGRP release from isolated primary sensory dorsal root ganglion neurons is dependent on protein kinase A and Raf-1 kinase. Our data indicate that, in addition to neural system adaptations, sustained opioid agonist treatment also produces intracellular compensatory adaptations in primary sensory neurons, leading to augmentation of evoked pain neurotransmitter release from these cells. The American Society for Pharmacology and Experimental Therapeutics