 |
The Journal of Neuroscience, November 26, 2003, 23(34):10988-10997
 Previous Article
Behavioral/Systems/Cognitive
Peptidergic Nociceptors of Both Trigeminal and Dorsal Root Ganglia Express Serotonin 1D Receptors: Implications for the Selective Antimigraine Action of Triptans
Sonja Potrebic,1,4 *
Andrew H. Ahn,1,2,4 *
Kate Skinner,2,4
Howard L. Fields,1,3,4 and
Allan I. Basbaum2,3,4
Departments of 1Neurology, 2Anatomy, and 3Physiology and 4W. M. Keck Foundation Center for Integrative Neurosciences, University of California, San Francisco, San Francisco, California 94143
Agonists at serotonin 1D (5-HT1D) receptors relieve migraine headache but are not clinically used as general analgesics. One possible explanation for this difference is that 5-HT1D receptors are preferentially expressed by cranial afferents of the trigeminal system. We compared the distribution of 5-HT1D receptor-immunoreactive (5-HT1D-IR) peripheral afferents within the trigeminal ganglion (TRG) and lumbar dorsal root ganglion (DRG) of the rat. We also examined the neurochemical identity of 5-HT1D-IR neurons with markers of primary afferent nociceptors, peripherin, isolectin B4, and substance P, and markers of myelinated afferents, N52 and SSEA3. We observed a striking similarity in the size, distribution, and neurochemical identity of 5-HT1D-IR neurons in TRG and lumbar DRG afferents. Furthermore, the vast majority of 5-HT1D-IR neurons are unmyelinated peptidergic afferents that distribute peripherally, including the dura, cornea, and the sciatic nerve. In the central projections of these afferents within the trigeminal nucleus caudalis and the spinal cord dorsal horn, 5-HT1D-IR fibers are concentrated in laminas I and outer II; a few axons penetrate to lamina V. At the ultrastructural level, 5-HT1D receptors in the spinal cord dorsal horn are localized exclusively within dense core vesicles of synaptic terminals. We observed scattered 5-HT1D-IR neurons in the nodose ganglia, and there was sparse terminal immunoreactivity in the solitary nucleus. The visceral efferents of the superior cervical ganglia did not contain 5-HT1D immunoreactivity. Our finding, that 5-HT1D receptors are distributed in nociceptors throughout the body, raises the possibility that triptans can regulate not only headache-associated pain but also nociceptive responses in extracranial tissues.
Key words: serotonin receptor; substance P; migraine pain; trigeminal; dorsal root ganglion; ultrastructure
Received June 30, 2003;
revised September 26, 2003;
accepted September 29, 2003.
This article has been cited by other articles:
|
|
|
|
 
D. J. Cavanaugh, H. Lee, L. Lo, S. D. Shields, M. J. Zylka, A. I. Basbaum, and D. J. Anderson
Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli
PNAS,
June 2, 2009;
106(22):
9075 - 9080.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. J. Lever, M. Robinson, M. Cibelli, C. Paule, P. Santha, L. Yee, S. P. Hunt, B. F. Cravatt, M. R. Elphick, I. Nagy, et al.
Localization of the Endocannabinoid-Degrading Enzyme Fatty Acid Amide Hydrolase in Rat Dorsal Root Ganglion Cells and Its Regulation after Peripheral Nerve Injury
J. Neurosci.,
March 25, 2009;
29(12):
3766 - 3780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hudmon, J.-S. Choi, L. Tyrrell, J. A. Black, A. M. Rush, S. G. Waxman, and S. D. Dib-Hajj
Phosphorylation of Sodium Channel Nav1.8 by p38 Mitogen-Activated Protein Kinase Increases Current Density in Dorsal Root Ganglion Neurons
J. Neurosci.,
March 19, 2008;
28(12):
3190 - 3201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-Q. Zhao, S. Chiechio, Y.-G. Sun, K.-H. Zhang, C.-S. Zhao, M. Scott, R. L. Johnson, E. S. Deneris, K. J. Renner, R. W. Gereau IV, et al.
Mice Lacking Central Serotonergic Neurons Show Enhanced Inflammatory Pain and an Impaired Analgesic Response to Antidepressant Drugs
J. Neurosci.,
May 30, 2007;
27(22):
6045 - 6053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Jimenez-Trejo, M. Tapia-Rodriguez, D. B. C. Queiroz, P. Padilla, M. C. W. Avellar, P. R. Manzano, G. Manjarrez-Gutierrez, and G. Gutierrez-Ospina
Serotonin Concentration, Synthesis, Cell Origin, and Targets in the Rat Caput Epididymis During Sexual Maturation and Variations Associated With Adult Mating Status: Morphological and Biochemical Studies
J Androl,
January 1, 2007;
28(1):
136 - 149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Ahn and A. I. Basbaum
Tissue Injury Regulates Serotonin 1D Receptor Expression: Implications for the Control of Migraine and Inflammatory Pain.
J. Neurosci.,
August 9, 2006;
26(32):
8332 - 8338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Strassman and D. Levy
Response Properties of Dural Nociceptors in Relation to Headache
J Neurophysiol,
March 1, 2006;
95(3):
1298 - 1306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Silberstein, R. B. Lipton, and N. M. Ramadan
From migraine mechanisms to innovative therapeutic drugs
Neurology,
May 24, 2005;
64(10_suppl_2):
S1 - S3.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Burstein and M. Jakubowski
Implications of multimechanism therapy: When to treat?
Neurology,
May 24, 2005;
64(10_suppl_2):
S16 - S20.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. M. Flake, D. B. Bonebreak, and M. S. Gold
Estrogen and Inflammation Increase the Excitability of Rat Temporomandibular Joint Afferent Neurons
J Neurophysiol,
March 1, 2005;
93(3):
1585 - 1597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Levy, M. Jakubowski, and R. Burstein
Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT1B/1D receptor agonists
PNAS,
March 23, 2004;
101(12):
4274 - 4279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
