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In a previous study, we demonstrated that inflammation suppressed inward rectifying K + (Kir) currents in satellite glial cells (SGCs) from the trigeminal ganglia (TRGs) and that this impairment of glial potassium homeostasis in the trigeminal ganglion (TRG) contributed to trigeminal pain. The aim of the present study was to investigate whether activation of GABA B receptors modulates the Kir current in SGCs using in vivo patch-clamp and immunohistochemical techniques. Immunohistochemically, we found that immunoreactivity for glial-specific Kir channel subunit Kir4.1 and the GABA B receptor was co-expressed in SGCs from the TRGs. In vivo whole-cell recordings were made using SGCs from the TRGs of urethane-anesthetized rats. Application of baclofen, a GABA B receptor agonist, significantly increased the mean peak amplitude of Kir currents in a concentration-dependent and reversible manner. Baclofen-induced potentiation of the Kir current was abolished by co-application of 3-amino-2-(4-chlorophenyl)-2-hydroxyprophylsulfonic acid (saclofen). In addition, baclofen significantly potentiated the density of the Ba 2+ -sensitive Kir current, and resulted in hyperpolarization of the mean membrane potential. These results suggest that activation of GABA B receptors potentiates the Kir current in SGCs and that GABA released from the TRG neuronal soma could contribute to buffering of extracellular K + concentrations following excitation of TRG neurons during the processing of sensory information, including the transmission of noxious stimuli.

The aim of the present study was to investigate the effect of temporomandibular joint inflammation on the excitability of trigeminal root ganglion neurons innervating the temporomandibular joint using a perforated patch-clamp technique. Inflammation was induced by injection of complete Freund's adjuvant into the rat temporomandibular joint. The threshold for escape from mechanical stimulation in the temporomandibular joint-inflamed rats was significantly lower than that in control rats. Fluorogold labeling was used to identify the trigeminal root ganglion neurons innervating the site of inflammation. When voltage-clamp (V(h)=-60 mV) conditions were applied to these Fluorogold-labeled small diameter trigeminal root ganglion neurons (

The aim of the present study was to investigate the effect of a micro-opioid receptor agonist DAMGO (Tyr-d-Ala-Gly-NMe-Phe-Gly-ol) on the excitability of trigeminal root ganglion (TRG) neurons, projecting onto the superficial layer of the cervical dorsal horn, by using the perforated-patch technique and to determine whether TRG neurons show the expression of mRNA or functional protein for micro-opioid receptors by using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. TRG neurons projecting onto the superficial layer of the cervical dorsal horn were retrogradely labeled with Fluorogold (FG). The cell diameter of FG-labeled TRG neurons was small (

The aim of the study was to examine the effects of alpha(2)-adrenoreceptor agonists on the excitability of trigeminal root ganglion (TRG) neurons using the perforated patch-clamp technique, and to determine whether these neurons express mRNA for alpha(2)-adrenoreceptors. In current-clamp mode, the resting membrane potential was -57.4+/-1.2 mV (n=26). Most neurons (71%) were hyperpolarized by clonidine (5-50 microM) in a concentration-dependent manner. The response was associated with an increase of cell input resistance. In addition, clonidine reduced the repetitive firing evoked by depolarizing current pulses. An alpha(2)-adrenergic agonist, UK14,304, (10-20 microM) also hyperpolarized TRG neurons. The clonidine- and UK14,304-induced hyperpolarization was blocked by idazoxan (alpha(2)-adrenoreceptor antagonist). In voltage-clamp, clonidine (1-50 microM) reversibly reduced the hyperpolarization- and time-dependent cationic current. The effect was mimicked by UK14,304 (10-20 microM), and antagonized by idazoxan. Hyperpolarization-activated cationic current was blocked by extracellular Cs(+) (2 mM) or a specific blocker, ZD7288 (20 microM). Analysis of tail currents revealed that a reversal potential of the clonidine-sensitive component of hyperpolarization-activated cationic current was -46 mV. Single-cell reverse transcription-polymerase chain reaction analysis demonstrated the expression of mRNA for alpha(2A)- and alpha(2C)-adrenoreceptors. These results demonstrate that activation of alpha(2)-adrenoreceptors can hyperpolarize TRG neurons, and that the inhibitory effect is associated with inhibition of hyperpolarization-activated cationic current. Our results suggest that activation of alpha(2)-adrenoreceptors in the absence of nerve injury may have an inhibitory effect on nociceptive transmission in the trigeminal system at the level of both TRG neuronal cell bodies and primary afferent terminals.

We recently indicated that brain-derived neurotrophic factor (BDNF) enhances the excitability of small-diameter trigeminal ganglion (TRG) neurons projecting onto the trigeminal nucleus interpolaris/caudalis (Vi/Vc) transition zone via a paracrine mechanism following masetter muscle (MM) inflammation. The present study investigated whether modulation of voltage-gated potassium (K) channels by BDNF contributes to this hyperexcitability effect. To induce inflammation we injected complete Freund's adjuvant (CFA) into the MM. The escape threshold from mechanical stimulation applied to skin above the inflamed MM was significantly lower than in naive rats. TRG neurons innervating the site of inflammation were subsequently identified by fluorogold (FG) labeling, and microbeads (MB) were used to label neurons projecting specifically to the Vi/Vc region. BDNF significantly decreased the total, transient (IA), and sustained (IK) currents in FG-/MB-labeled small-diameter TRG neurons under voltage-clamp conditions in naive and inflamed rats. The magnitude of inhibition of IA and IK currents by BDNF in FG-/MB-labeled TRG neurons was significantly greater in inflamed rats than in naive rats, and BDNF inhibited IA to a significantly greater extent than IK. Furthermore, co-administration of K252a, a tyrosine kinase inhibitor, abolished the suppression of IA and IK currents by BDNF. These results suggested that the inhibitory effects of BDNF on IA and IK currents in small-diameter TRG neurons projecting onto the Vi/Vc potentiate neuronal excitability, and in turn, contribute to MM inflammatory hyperalgesia. These findings support the development of voltage-gated K(+) channel openers and tyrosine kinase inhibitors as potential therapeutic agents for the treatment of trigeminal inflammatory hyperalgesia.

The aims of the present study were to investigate whether the activation of the 5-HT receptor subtypes (5-HT(4) and 5-HT(3)) acted significantly on the modification of the tetrodotoxin-resistant sodium current (I(NaR)) in small-sized rat trigeminal ganglion (TG) neurons and whether the inhibition of the transient K(+) current (I(A)) contributed to the excitability in those neurons. 5-HT applications in at concentrations ranging from 0.01-10 microM significantly increased the peak I(NaR). One micromolar 5-HT application caused the greatest increase in the peak I(NaR) amplitude accompanied by a hyperpolarizing shift in the activation curve. A similar modification of I(NaR) properties was also obtained via the application of the 5-HT(4) receptor agonist, RS 67333, in concentrations ranging from 0.001-1 microM. The largest effects of 5-HT (1 microM) and RS 67333 (0.1 microM) on the modification of I(NaR) were abolished by pretreatment with ICS 205-930 (a 5-HT(3/4) receptor antagonist, 10 microM), which showed no significant effect on the baseline I(NaR). However, ICS 205-930 application at 30 microM caused a significant decrease in the baseline I(NaR). Phenylbiguanide (a 5-HT(3) receptor agonist) did not significantly alter I(NaR) properties when applied in concentrations ranging from 1 to 100 microM. The application of 0.1 microM RS 67333 decreased the transient K(+) current (I(A)) by approximately 31%. The threshold for action potential generation was significantly lower after the application of 0.1 microM RS 67333. Furthermore, 0.1 microM RS 67333 application increased the number of action potentials and the resting membrane potential got more positive, but it decreased the duration of depolarization phase of action potential. In addition, neither the additional application of 1 microM 5-HT in the presence of 10 microM forskolin, a stimulator of adenylyl cyclase, nor the opposite applications of 5-HT and forskolin caused the enhancement of increased I(NaR), which indicates the presence of an 'occluding effect.' These results suggest that the 5-HT-induced modification of I(NaR) is mediated by the activation of 5-HT(4) receptors, involving a cAMP-dependent signaling pathway, and that the inhibition of I(A) following the application of a 5-HT(4) receptor agonist also contributes to the increased number of action potentials.

A selective GABA(B) receptor agonist, baclofen, is known to suppress neuropathic pain. In the present study, we investigated the effect of baclofen on the excitability of trigeminal root ganglion (TRG) neurons by using the whole cell and perforated patch-clamp recording techniques. Under voltage-clamp (V(h)=-60 mV), voltage-dependent K(+) currents were recorded in the small diameter TRG neurons (