| First Author | Schuster DJ | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 33 | Pages | 13538-46 |
| PubMed ID | 23946412 | Mgi Jnum | J:353750 |
| Mgi Id | MGI:6837022 | Doi | 10.1523/JNEUROSCI.4013-12.2013 |
| Citation | Schuster DJ, et al. (2013) Protein kinase Cepsilon is required for spinal analgesic synergy between delta opioid and alpha-2A adrenergic receptor agonist pairs. J Neurosci 33(33):13538-46 |
| abstractText | We recently showed that spinal synergistic interactions between delta opioid receptors (deltaORs) and alpha2A adrenergic receptors (alpha2AARs) require protein kinase C (PKC). To identify which PKC isoforms contribute to analgesic synergy, we evaluated the effects of various PKC-isoform-specific peptide inhibitors on synergy between deltaORs and alpha2AARs using the tail flick assay of thermal nociception in mice. Only a PKCepsilon inhibitor abolished synergy between a deltaOR agonist and an alpha2AAR agonist. We tested a panel of combinations of opioid and adrenergic agonists in PKCepsilon knock-out mice and found that all four combinations of a deltaOR agonist and an alpha2AAR agonist required PKCepsilon for antinociceptive synergy. None of the combinations of a muOR agonist with an alpha2AR agonist required PKCepsilon. Immunohistochemistry confirmed that PKCepsilon could be found in the population of peptidergic primary afferent nociceptors where deltaORs and alpha2AARs have been found to extensively colocalize. Immunoreactivity for PKCepsilon was found in the majority of dorsal root ganglion neurons and intensely labeled laminae I and II of the spinal cord dorsal horn. PKCepsilon is widespread in the spinal nociceptive system and in peptidergic primary afferents it appears to be specifically involved in mediating the synergistic interaction between deltaORs and alpha2AARs. |
