Somatostatin inhibits the excitability of rat small-diameter trigeminal ganglion neurons that innervate nasal mucosa and project to the upper cervical dorsal horn via activation of somatostatin 2a receptor.
This study investigated whether somatostatin (SST) modulates the excitability of nociceptive trigeminal ganglion (TRG) neurons that innervate the nasal mucosa and project to the upper cervical (C(1)) dorsal horn by using perforated-patch clamping, retrograde-labeling, and immunohistochemistry. Fluorogold (FG) retrograde labeling was used to identify the rat TRG neurons innervating the nasal mucosa, while microbeads (MB) were used to label neurons projected onto the superficial layer of the C(1) dorsal horn. FG-labeled small-diameter TRG neurons exhibited SST(2A) receptor immunoreactivity (19%) and half of these neurons were also labeled with MB. In whole-cell current-clamp mode, most (72%) of the dissociated FG-/MB-labeled TRG neurons were hyperpolarized by application of SST. The hyperpolarization was evoked by SST in a concentration-dependent manner (0.1-10 microM) and the responses were associated with a decrease in the cell input resistance. The minimum concentration to elicit a significant hyperpolarization was 1 microM. The repetitive firings during a depolarizing pulse were significantly reduced by SST (1 microM) application. The hyperpolarization and decreased firing evoked by SST were both blocked by the SST(2) receptor antagonist, CYN154806 (1 microM). Under voltage-clamp conditions, SST (1 microM) significantly increased the voltage-gated K(+) transient (I(A)) and sustained (I(K)) currents and these increases were abolished by coapplication of CYN154806 (1 microM). In the presence of both 4-aminopyridine (6 mM) and tetraethylammonium (10 mM), no significant changes in the membrane potential in response to SST application were found. These results suggest that modulation of trigeminal nociceptive transmission in the C(1) dorsal horn by activation of SST(2A) receptors occurs at the level of small-diameter TRG cell bodies and/or their afferent terminals, and that this may be related to regulation of protective upper-airway reflexes.
Takeda
M
M
Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan. m-takeda@tokyo.ndu.ac.jp
Kadoi
J
J
Takahashi
M
M
Nasu
M
M
Matsumoto
S
S
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009297:Nasal Mucosa / Q000294:innervation*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D013266:Stilbamidines; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; C403089:CYN 154806; D009842:Oligopeptides; D017481:Receptors, Somatostatin; D013266:Stilbamidines; C106140:somatostatin receptor sst2A; D013004:Somatostatin