Opioid presynaptic disinhibition of the midbrain periaqueductal grey descending analgesic pathway
Autor: | Christopher W. Vaughan, Bryony L. Winters, Benjamin K. Lau |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Agonist medicine.drug_class Postsynaptic Current Receptors Opioid mu Inhibitory postsynaptic potential Synaptic Transmission Rats Sprague-Dawley Midbrain 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Postsynaptic potential Current clamp medicine Animals Periaqueductal Gray Patch clamp Pharmacology Analgesics Enkephalin Ala(2)-MePhe(4)-Gly(5) Research Papers Rats Analgesics Opioid DAMGO 030104 developmental biology nervous system chemistry Neuroscience 030217 neurology & neurosurgery |
Zdroj: | Br J Pharmacol |
ISSN: | 1476-5381 0007-1188 |
Popis: | BACKGROUND AND PURPOSE: The midbrain periaqueductal grey (PAG) plays a central role in modulating pain through a descending pathway that projects indirectly to the spinal cord via the rostroventral medial medulla (RVM). While opioids are potent analgesics that target the PAG, their cellular actions on descending projection neurons are unclear. EXPERIMENTAL APPROACH: Patch clamp recordings in voltage‐ and current‐clamp mode were made from acutely prepared PAG slices from animals that received retrograde tracer injections into the RVM. KEY RESULTS: The μ‐agonist DAMGO reduced GABAergic evoked inhibitory postsynaptic currents (IPSCs) in retro‐labelled, RVM‐projecting neurons to a greater extent than in unlabelled neurons. The κ‐opioid agonist U69593 reduced evoked IPSCs to a similar extent in both neuronal groups, while the δ‐opioid agonist deltorphin‐II was without effect. DAMGO and U69593 both produced a reduction in the rate, but not amplitude of spontaneous miniature IPSCs and asynchronous evoked IPSCs in retro‐labelled neurons. DAMGO and U69593 also suppressed glutamatergic EPSCs in retro‐labelled and unlabelled neurons. The DAMGO inhibition of evoked EPSCs, however, was less than that for evoked IPSCs in retro‐labelled, but not unlabelled neurons. In current clamp, DAMGO produced a depolarizing increase in evoked postsynaptic potentials in retro‐labelled neurons, but directly inhibited unlabelled neurons. CONCLUSION AND IMPLICATIONS: These findings suggest that μ‐opioids activate the descending analgesic pathway from the midbrain PAG by a combination of presynaptic disinhibition of RVM‐projecting neurons and postsynaptic inhibition of presumptive interneurons. |
Databáze: | OpenAIRE |
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