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.
Wrigley
Paul J
PJ
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
Jeong
Hyo-Jin
HJ
Vaughan
Christopher W
CW
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