Hyperpolarization of substantia gelatinosa neurons evoked by μ-, κ-, δ1-, and δ2-selective opioids

Abstract

With whole-cell recordings of substantia gelatinosa (SG) neurons from rat spinal cord slices, we investigated the effects of bath application of highly selective δ1, δ2, κ and μ opioid agonists on membrane potential and conductance. Each agonist was applied at 0.5 to 1 μmol/L and evoked robust hyperpolarizations and conductance increases in a subset of neurons. The response magnitude means were similar across agonists at several concentrations; no excitatory effects were observed. Nine of 55 (16%) were hyperpolarized by δ1 opioids, 2 of 45 (4%) by δ2, 8 of 59 (14%) by κ, and 35 of 67 (52%) by μ opioids. To test the hypothesis that SG neurons may be hyperpolarized by multiple opioid subtype agonists, we applied 2, 3, or 4 selective agonists to individual neurons. Most neurons were hyperpolarized only by μ opioids; however, a minority were hyperpolarized by multiple subtype-selective agonists. These results indicate that δ1- and δ2-selective opioids can also evoke robust hyperpolarizations in spinal SG neurons, that the relative abundance of hyperpolarizing responses was μ ⪢ δ1 ≃ κ > δ2, and that some SG neurons can be hyperpolarized by more than 1 opioid subtype-selective agonist. These powerful inhibitory postsynaptic responses likely contribute to analgesia evoked by spinally and systemically administered opioid subtype-selective agonists. © 2002 by the American Pain Society