Selective postsynaptic inhibition of tonic-firing neurons in substantia gelatinosa by mu-opioid agonist.
BACKGROUND
Spinal substantia gelatinosa (SG) is a site of action of administered and endogenous opioid agonists and is an important element in the system of antinociception. However, little is known about the types of neurons serving as specific postsynaptic targets for opioid action within the SG. To study the spinal mechanisms of opioidergic analgesia, the authors compared the action of mu-opioid agonist [D-Ala, N-Me-Phe, Gly-ol]-enkephalin (DAMGO) on SG neurons with different intrinsic firing properties.


METHODS
Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the sensitivity of SG neurons to DAMGO.


RESULTS
Three groups of neurons with distinct distributions in SG were classified: tonic-, adapting-, and delayed-firing neurons. DAMGO at 1 microm concentration selectively hyperpolarized all tonic-firing neurons tested, whereas none of the adapting- or delayed-firing neurons were affected. The effect of DAMGO on tonic-firing neurons was due to activation of G protein-coupled inward-rectifier K conductance, which could be blocked by 500 microm Ba and 500 microm Cs but increased by 50 microm baclofen. As a functional consequence of DAMGO action, a majority of tonic-firing neurons changed their pattern of intrinsic firing from tonic to adapting.


CONCLUSIONS
It is suggested that tonic-firing neurons, presumably functioning as excitatory interneurons, are primary postsynaptic targets for administered and endogenous opioid agonists in spinal SG. Functional transition of cells in this group from tonic to adapting firing mode may represent an important mechanism facilitating opioidergic analgesia.
Santos
Sónia F A
SF
Departamento de Neurobiologia Básica e Clínica, Instituto de Biologia Molecular e Celular, and Instituto de Histologia e Embriologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Melnick
Igor V
IV
Safronov
Boris V
BV
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D002586:Cesium / Q000494:pharmacology; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists*; D017661:Receptors, Presynaptic / Q000187:drug effects*; D013376:Substantia Gelatinosa / Q000187:drug effects*
D000701:Analgesics, Opioid; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists; D024661:Potassium Channels, Inwardly Rectifying; D017450:Receptors, Opioid, mu; D017661:Receptors, Presynaptic; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002586:Cesium; D001464:Barium; D001418:Baclofen