The excitability of the second order neurons within the trigeminal subnucleus caudalis underlies pain perception and processing in migraine and trigeminal neuralgia. These neurons were studied with whole-cell patch-clamp technique in slices from mouse brain stem. Electrical and morphological characteristics of 56 neurons were determined. Four categories were distinguished from electrophysiological properties: tonic (39%), phasic (34%), delayed (16%) and single spiking (11%). These categories did not show distinct morphological properties. Neurons had tetrodotoxin-sensitive sodium currents that activated and inactivated within milliseconds. They also showed a high voltage-activated, slowly inactivating calcium current: up to half of this current was blocked by ω-conotoxin GVIA (1 μM) and ω-agatoxin IVA (100–300 nM), but it was not affected by nifedipine (10 μM). Exogenously applied capsaicin (1 μM) and αβmethylene-5′-adenosine triphosphate (100 μM) elicited large amplitude, spontaneous excitatory postsynaptic currents that were blocked by capsazepine (10 μM) and 5-[(3-phenoxybenzyl)-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-benzene-1,2,4-tricarboxylic acid (A-317491: 10 μM), respectively. Thus, neurons of the mouse trigeminal subnucleus caudalis substantia gelatinosa exhibit N-type and P/Q-type voltage-gated calcium channels, and receive presynaptic afferents that express TRPV1 and P2X2/3 receptors. These results suggest possible therapeutic interventions, and serve as a basis for the characterization of cellular changes that may underlie trigeminal neuropathic pain.
aFaculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
bFaculty of Medical and Human Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
*Corresponding author. Address: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. Tel.: +44 161 275 1499; fax: +44 161 275 1498.
Received April 10, 2009; Received in revised form July 7, 2009; Accepted July 28, 2009.