Neuropeptide Y inhibits capsaicin-sensitive nociceptors via a Y1-receptor-mediated mechanism.
Neuropeptide Y (NPY) is expressed in certain primary afferent fibers, is up-regulated in response to tissue injury and is capable of inhibiting nociceptive behavior at the spinal level. However, the spinal mechanism(s) for NPY-evoked antinociception is unknown. In this study, we evaluated the hypothesis that agonists at the NPY Y1 receptor subtype (Y1-R) inhibit exocytosis from the capsaicin-sensitive class of nociceptors. Using in vitro superfusion of rat dorsal spinal cord slices, pre-treatment with the Y1-R agonist [Leu(31)Pro(34)]NPY significantly inhibited capsaicin-evoked release of immunoreactive calcitonin gene-related peptide with an EC(50) value of 10.6 nM. This inhibitory effect was concentration dependent, significantly attenuated by pre-treatment with the Y1 receptor antagonist BIBP3226 and reproduced by synthetic NPY. Examination of adult rat dorsal root ganglia using double immunofluorescent labeling revealed frequent co-localization of Y1 receptor immunoreactivity in vanilloid receptor type 1-immunoreactive neurons, indicating that Y1 agonists may directly modulate the capsaicin-sensitive class of nociceptors. Collectively, these results indicate that NPY is capable of inhibiting capsaicin-sensitive neurons via a Y1 receptor mechanism, suggesting the mechanisms for spinal NPY-induced antinociception is due, at least in part, to inhibition of central terminals of capsaicin-sensitive nociceptors.
Gibbs
J
J
Departments of Endodontics and Pharmacology, The University of Texas Health Science Center at San Antonio, Mail Code 7892, 7703 Floyd Curl Lane, San Antonio, TX 78229-3900, USA. gibbs@uthscsa.edu
Flores
C M
CM
Hargreaves
K M
KM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism
D000700:Analgesics; C092926:BIBP 3226; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011955:Receptors, Drug; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin