Opioid peptides modulate the response of neurons of the superficial laminae of the rat spinal dorsal horn to GABA

Abstract

The modulatory effects of methionine-enkephalin (M-ENK) and selective opioid-receptor agonists on GABA-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae of the rat spinal dorsal horn using nystatin-perforated patch recording configuration under voltage-clamp conditions. The results show that: (1) GABA acted on GABA A receptors and elicited inward Cl − currents ( I GABA) at −60 mV; (2) M-ENK depressed I GABA in ∼65% of the tested neurons and potentiated I GABA in ∼15% of the neurons tested; (3) the agonists of μ-, κ-, and δ-opioid receptors—[ d-AIa 2, N-Me-Phe 4,Gly 5-ol]-enkephalin (DAMGO), dynorphin-A (Dyn-A), and [ d-Pen 2, d-Pen 5]-enkephalin (DPDPE) also depressed the I GABA, and the order of agonist potency was DAMGO > Dyn-A > DPDPE; and (4) naloxone blocked the inhibitory effects of M-ENK on I GABA. The antagonists of μ-, κ-, and δ-opioid receptors—β-funaltrexamine (β-FNA), nor-binaltorphimine (nor-BNI), and naltrindole (NTI) prevented the DAMGO-, Dyn-A-, and DPDPE-induced depression of I GABA. The results suggest that M-ENK downregulates I GABA principally through μ- and κ-opioid receptors, and thus exerts its modulating effects indirectly on the transmission of noxious information at the spinal level.