Fentanyl decreases Ca2+ currents in a population of capsaicin-responsive sensory neurons.
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 (I Ca ) in primary nociceptive neurons, identified by their response to the algogenic agent capsaicin.


METHODS
I was recorded from acutely isolated rat dorsal root ganglion neurons using the whole cell patch clamp technique before, during, and after application of the micro -opioid agonist fentanyl (0.01-1 micro m). Capsaicin was applied to each cell at the end of the experiment.


RESULTS
Fentanyl reduced I Ca 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 I Ca was 38 +/- 3% (n = 36, 1 micro m) in fentanyl-sensitive cells just 7 +/- 1% (n = 15, 1 micro m; P < 0.05) in fentanyl-insensitive cells. Among capsaicin-responsive cells, I Ca inactivated more rapidly in fentanyl-sensitive cells (tau, 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 omega-conotoxin GVIA-sensitive (N-type), nifedipine-sensitive (L-type), and GVIA/nifedipine-resistant (primarily P-/Q-type) components of I Ca 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.
McDowell
Thomas S
TS
Department of Anesthesiology, University of Wisconsin Medical School, Madison, Wisconsin 53792-3272, USA. tsmcdowe@facstaff.wisc.edu
D060848:Agatoxins; D000465:Algorithms; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005283:Fentanyl / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects; D013111:Spider Venoms / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D060848:Agatoxins; D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011955:Receptors, Drug; D013111:Spider Venoms; D020960:omega-Conotoxins; C083855:omega-agatoxin-Aa4b; C075851:omega-conotoxin-MVIIC; D002211:Capsaicin; D005283:Fentanyl