Interleukin-2 regulates membrane potentials and calcium channels via mu 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 μ 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 (10³ U/ml) produced membrane hyperpolarization of –9.4 ± 3.0 mV and this effect was blocked by β-FNA (5 μM), a μ 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 μM). Consistent with previous studies, DAMGO, a selective μ opioid agonist, exerted similar inhibitory effects on membrane potentials and Ca²⁺ currents.

The present results indicated that μ 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.