RT Journal Article
SR Electronic
T1 Presynaptic Mechanism for Anti-Analgesic and Anti-Hyperalgesic Actions of κ-Opioid Receptors
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7262
OP 7268
DO 10.1523/JNEUROSCI.23-19-07262.2003
VO 23
IS 19
A1 Bie, Bihua
A1 Pan, Zhizhong Z.
YR 2003
UL http://www.jneurosci.org/content/23/19/7262.abstract
AB Glutamate neurotransmission plays an important role in the processing of pain and in chronic opioid-induced neural and behavioral plasticity, such as opioid withdrawal and opioid dependence. κ-Opioid receptors also have been implicated in acute opioid modulation of pain and chronic opioid-induced plasticity, both of which are primarily mediated by μ-opioid receptors. Using whole-cell patch clamp recordings in brain slices in vitro and system analysis of pain behaviors in rats in vivo, this study investigated the functional role of glutamate synaptic transmission andκ-opioid receptors in two behavioral pain conditions:μ-opioid-induced analgesia (decreased pain) and μ-opioid withdrawal-induced hyperalgesia (increased pain). In the nucleus raphe magnus (NRM), a brainstem structure that controls spinal pain transmission, we found thatκ-receptor agonists presynaptically inhibited glutamate synaptic currents in both of the two cell types that are thought to respectively inhibit or facilitate spinal pain transmission. In rats, both glutamate receptor antagonists and the κ agonist microinjected into the NRM attenuated μ-opioid-induced analgesia, which is most likely mediated through activation of such pain-inhibiting neurons. However, during opioid abstinence-induced withdrawal, the same doses of glutamate receptor antagonists and the κ agonist administered in the NRM suppressed the withdrawal-induced hyperalgesia, which is thought to be mediated by activation of those pain-facilitating neurons during opioid withdrawal. These results demonstrate that κ-opioid receptors antagonize μ-receptor-induced effects in both analgesic and hyperalgesic states, and suggest inhibition of glutamate synaptic transmission as a presynaptic mechanism for the κ antagonism of these two μ receptor-mediated actions.