BACKGROUND: Opioids inhibit excitatory neurotransmission and produce antinociception through μ opioid receptors (MORs). Although MORs are expressed in the spinal ventral horn, their functions and effects are largely unknown. Therefore, we examined the neuromodulatory effects of μ opioids in spinal lamina IX neurons at the cellular level. METHODS: The effects of the selective μ agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO) on synaptic transmission were examined in spinal lamina IX neurons of neonatal rats using the whole-cell patch-clamp technique. RESULTS: DAMGO produced outward currents in 56% of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 μM. Analysis of the current-voltage relationship revealed a reversal potential of approximately -86 mV. These currents were not blocked by tetrodotoxin but were inhibited by Ba(2+) or a selective μ antagonist. Moreover, the currents were suppressed by the addition of Cs(+) and tetraethylammonium or guanosine 5'-[β-thio]diphosphate trilithium salt to the pipette solution. In addition, DAMGO decreased the frequency of spontaneous excitatory and inhibitory postsynaptic currents, and these effects were unaltered by treatment with tetrodotoxin. CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX neurons by G protein-mediated activation of K(+) channels after activation of MORs. Furthermore, activation of MORs on presynaptic terminals reduces both excitatory and inhibitory transmitter release. Although traditionally opioids are not thought to affect motor function, the present study documents neuromodulatory effects of μ opioids in spinal lamina IX neurons, suggesting that MORs can influence motor activity.
BACKGROUND: Opioids inhibit excitatory neurotransmission and produce antinociception through μ opioid receptors (MORs). Although MORs are expressed in the spinal ventral horn, their functions and effects are largely unknown. Therefore, we examined the neuromodulatory effects of μ opioids in spinal lamina IX neurons at the cellular level. METHODS: The effects of the selective μ agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO) on synaptic transmission were examined in spinal lamina IX neurons of neonatal rats using the whole-cell patch-clamp technique. RESULTS: DAMGO produced outward currents in 56% of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 μM. Analysis of the current-voltage relationship revealed a reversal potential of approximately -86 mV. These currents were not blocked by tetrodotoxin but were inhibited by Ba(2+) or a selective μ antagonist. Moreover, the currents were suppressed by the addition of Cs(+) and tetraethylammonium or guanosine 5'-[β-thio]diphosphate trilithium salt to the pipette solution. In addition, DAMGO decreased the frequency of spontaneous excitatory and inhibitory postsynaptic currents, and these effects were unaltered by treatment with tetrodotoxin. CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX neurons by G protein-mediated activation of K(+) channels after activation of MORs. Furthermore, activation of MORs on presynaptic terminals reduces both excitatory and inhibitory transmitter release. Although traditionally opioids are not thought to affect motor function, the present study documents neuromodulatory effects of μ opioids in spinal lamina IX neurons, suggesting that MORs can influence motor activity.
Authors: Alexander I Pilyavskii; Waldemar Moska; Kazimir Kochanowicz; Natalia V Bulgakova; Andriy V Maznychenko; Inna V Vereshchaka; Alexander I Kostyukov Journal: Front Neurosci Date: 2013-12-17 Impact factor: 4.677
Authors: Barbara Palkovic; Jennifer J Callison; Vitaliy Marchenko; Eckehard A E Stuth; Edward J Zuperku; Astrid G Stucke Journal: Anesthesiology Date: 2021-10-01 Impact factor: 8.986