Functional expression of 5-HT⁷ receptor on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc; medullary dorsal horn) receives and processes orofacial nociceptive inputs, and serotonergic fibers involved in the descending modulation of nociception are more densely distributed in the superficial laminae of the Vc. This study investigated the direct effects of 5-HT(1A/7) receptor agonist 8-OH-DPAT on SG neurons of the Vc to assess functional expression of the 5-HT⁷ receptor using gramicidin-perforated patch-clamp in postnatal day (PND) 5-84 male mice. Of the 70 SG neurons tested, bath application of 8-OH-DPAT (30 μM) induced depolarization (n=33), hyperpolarization (n=16) or no response (n=21). In another 10 SG neurons, 8-OH-DPAT in the presence of 5-HT(1A) receptor antagonist WAY-100635 (1 μM) elicited either depolarization (n=6) or no response (n=4); hyperpolarization was not observed. The 8-OH-DPAT-induced depolarization was significantly blocked by the selective 5-HT⁷ receptor antagonist SB-269970 (10 μM; n=8), but not by WAY-100635 (1 μM; n=5). The depolarizing effect of 8-OH-DPAT was maintained in the presence of TTX, CNQX, AP5, picrotoxin, and strychnine, indicating direct postsynaptic action of 8-OH-DPAT on SG neurons (n=6). 5-HT⁷ receptor mRNA was also detected in five of 21 SG neurons by single-cell RT-PCR. The mean amplitude of 8-OH-DPAT-induced depolarization in PND 5-21 mice (n=21) was significantly larger than that in PND 22-84 mice (n=12), although the proportion of SG neurons responding to 8-OH-DPAT by depolarization did not differ significantly between two age groups of mice. These results indicate that 5-HT⁷ receptors are functionally expressed in a subpopulation of SG neurons of the Vc and activation of 5-HT⁷ receptors plays an important role in modulating orofacial nociceptive processing in the SG neurons of the Vc.