Interleukin-2 regulates membrane potentials and calcium channels via μ opioid receptors in rat dorsal root ganglion neurons

Our previous studies revealed that interleukin-2 (IL-2) exerted peripheral antinociception that was partially mediated by mu opioid receptors. No ionic explanations of this effect have yet been reported. The present study was designed to investigate effects of IL-2 on the physiological properties of capsaicin-sensitive small dorsal root ganglion (DRG) neurons, which are predominantly responsible for nociceptive transmission from the periphery to the spinal cord. Intracellualr recordings of DRG neurons were made in DRG/peripheral nerve preparation in vitro. IL-2 (10(3) U/ml) produced membrane hyperpolarization of -9.4 +/- 3.0 mV and this effect was blocked by beta-FNA (5 muM), a mu opioid receptor antagonist. Under whole-cell patch clamp recordings, transient high-threshold Ca2+ currents were inhibited by -56.6 +/- 11.3% by IL-2. Simultaneous calcium imaging showed that this cytokine also inhibited depolarization-evoked increase in intracellular calcium concentration. All the effects of IL-2 were blocked by naloxone (1 muM). Consistent with previous studies, DAMGO, a selective mu opioid agonist, exerted similar inhibitory effects on membrane potentials and Ca2+ currents. The present results indicated that g opioid receptors were involved in the regulatory effects of IL-2 on membrane potentials and calcium channels in DRG neurons, which may contribute to IL-2-induced peripheral analgesia. (C) 2002 Elsevier Science Ltd. All rights reserved.