Paradoxical Pain After Opioid Withdrawal

Science Signaling  14 Jul 2009:
Vol. 2, Issue 79, pp. ec240
DOI: 10.1126/scisignal.279ec240

Opioids are widely used by both pain patients and substance abusers. Withdrawal from opioids can be complicated by opioid-induced hyperalgesia, a paradoxical amplification of pain by opioids. Drdla et al. detected a novel cellular opioid action that may help to explain this paradoxical pain: the induction of synaptic long-term potentiation (LTP) in pain pathways by opioids. In vitro and in vivo μ-opioid receptor agonist withdrawal induced robust LTP at synapses of nociceptive C fibers. This is in contrast to the presynaptic inhibition by opioids at these synapses. Because opioidergic LTP and acute synaptic depression are spatially and mechanistically distinct, it may be possible to treat opioid-induced hyperalgesia selectively without compromising opioid analgesia.

R. Drdla, M. Gassner, E. Gingl, J. Sandkühler, Induction of synaptic long-term potentiation after opioid withdrawal. Science 325, 207–210 (2009). [Abstract] [Full Text]