Fentanyl decreases Ca2+ currents in a population of capsaicin-responsive sensory neurons

Abstract

Background: Neuraxial opioids produce analgesia in part by decreasing excitatory neurotransmitter release from primary nociceptive neurons, an effect that may be due to inhibition of presynaptic voltage-activated Ca2+ channels. The purpose of this study was to determine whether opioids decrease Ca2+ currents (ICa) in primary nociceptive neurons, identified by their response to the algogenic agent capsaicin. Methods: ICa was recorded from acutely isolated rat dorsal root ganglion neurons using the whole cell patch clamp technique before, during, and after application of the μ-opioid agonist fentanyl (0.01-1 μM). Capsaicin was applied to each cell at the end of the experiment. Results: Fentanyl reduced ICa in a greater proportion of capsaicin-responsive cells (62 of 106, 58%) than capsaicin-unresponsive cells (2 of 15, 13%; P < 0.05). Among capsaicin-responsive cells, the decrease in ICa was 38 ± 3% (n = 36, 1 μM) in fentanyl-sensitive cells versus just 7 ± 1% (n = 15, μM; P < 0.05) in fentanyl-insensitive cells. Among capsaicin-responsive cells, ICa inactivated more rapidly in fentanyl-sensitive cells (τh, 52 ± 4 ms, n = 22) than in fentanyl-insensitive cells (93 ± 14 ms, n = 24; P < 0.05). This was not due to differences in the types of Ca2+ channels expressed as the magnitudes of ω-conotoxin GVIA-sensitive (N-type), nifedipine-sensitive (L-type), and GVIA/nifedipine-resistant (primarily P-/Q-type) components of ICa were similar. Conclusions: The results show that opioid-sensitive Ca2+ channels are expressed by very few capsaicin-unresponsive neurons but by more than half of capsaicin-responsive neurons. The identity of the remaining capsaicin-responsive (and therefore presumed nociceptive) neurons that express opioid-insensitive Ca2+ channels is unknown but may represent a potential target of future non-opioid-based therapies for acute pain.