Induction of Synaptic Long-Term Potentiation After Opioid Withdrawal
Ruth Drdla,*
Matthias Gassner,*
Ewald Gingl,
Jürgen Sandkühler
µ-Opioid receptor (MOR) agonists represent the gold standard
for the treatment of severe pain but may paradoxically also
enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia
(OIH). We show that abrupt withdrawal from MOR agonists induces
long-term potentiation (LTP) at the first synapse in pain pathways.
Induction of opioid withdrawal LTP requires postsynaptic activation
of heterotrimeric guanine nucleotide–binding proteins
and
N-methyl-
D-aspartate receptors and a rise of postsynaptic
calcium concentrations. In contrast, the acute depression by
opioids is induced presynaptically at these synapses. Withdrawal
LTP can be prevented by tapered withdrawal and shares pharmacology
and signal transduction pathways with OIH. These findings provide
a previously unrecognized target to selectively combat pro-nociceptive
effects of opioids without compromising opioid analgesia.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: juergen.sandkuehler{at}meduniwien.ac.at
