Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn.
BACKGROUND
There is anatomical and behavioural evidence that μ- and δ-opioid receptors modulate distinct nociceptive modalities within the superficial dorsal horn. The aim of the present study was to examine whether μ- and δ-opioid receptor activation differentially modulates TRP sensitive inputs to neurons within the superficial dorsal horn. To do this, whole cell patch clamp recordings were made from lamina I - II neurons in rat spinal cord slices in vitro to examine the effect of opioids on TRP agonist-enhanced glutamatergic spontaneous miniature excitatory postsynaptic currents (EPSCs).


RESULTS
Under basal conditions the μ-opioid agonist DAMGO (3 μM) reduced the rate of miniature EPSCs in 68% of neurons, while the δ- and κ-opioid agonists deltorphin-II (300 nM) and U69593 (300 nM) did so in 13 - 17% of neurons tested. The TRP agonists menthol (400 μM) and icilin (100 μM) both produced a Ca2+-dependent increase in miniature EPSC rate which was unaffected by the voltage dependent calcium channel (VDCC) blocker Cd2+. The proportion of neurons in which deltorphin-II reduced the miniature EPSC rate was enhanced in the presence of icilin (83%), but not menthol (0%). By contrast, the proportion of DAMGO and U69593 responders was unaltered in the presence of menthol (57%, 0%), or icilin (57%, 17%).


CONCLUSIONS
These findings demonstrate that δ-opioid receptor activation selectively inhibits inputs activated by icilin, whereas μ-opioid receptor activation has a more widespread effect on synaptic inputs to neurons in the superficial dorsal horn. These findings suggest that δ-opioids may provide a novel analgesic approach for specific, TRPA1-like mediated pain modalities.
Pain Management Research Institute, Kolling Institute for Medical Research, Northern Clinical School, The University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia. paul.wrigley@sydney.edu.au
Paul J
PJ
Wrigley
Hyo-Jin
HJ
Jeong
Christopher W
CW
Vaughan
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008610:Menthol / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D015220:Calcium Channels; D005971:Glutamates; D011744:Pyrimidinones; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D008610:Menthol; C490483:icilin; D002118:Calcium