Activation of transient receptor potential vanilloid 1 (TRPV1), a calcium permeable channel expressed in primary sensory neurons, induces the release of glutamate from their central and peripheral afferents during normal acute and pathological pain. However, little information is available regarding the glutamate release mechanism associated with TRPV1 activation in primary sensory neurons. To address this issue, we investigated the expression of vesicular glutamate transporter (VGLUT) in TRPV1-immunopositive (+) neurons in the rat trigeminal ganglion (TG) under normal and complete Freund’s adjuvant (CFA)-induced inflammatory pain conditions using behavioral testing as well as double immunofluorescence staining with antisera against TRPV1 and VGLUT1 or VGLUT2. TRPV1 was primarily expressed in small and medium-sized TG neurons. TRPV1+ neurons constituted approximately 27% of all TG neurons. Among all TRPV1+ neurons, the proportion of TRPV1+ neurons coexpressing VGLUT1 (VGLUT1+/ TRPV1+ neurons) and VGLUT2 (VGLUT2+/TRPV1+ neurons) was 0.4% ± 0.2% and 22.4% ± 2.8%, respectively. The proportion of TRPV1+ and VGLUT2+ neurons was higher in the CFA group than in the control group (TRPV1+ neurons: 31.5% ± 2.5% vs. 26.5% ± 1.2%, VGLUT2+ neurons: 31.8% ± 1.1% vs. 24.6% ± 1.5%, p < 0.05), whereas the proportion of VGLUT1+, VGLUT1+/TRPV1+, and VGLUT2+/TRPV1+ neurons did not differ significantly between the CFA and control groups. These findings together suggest that VGLUT2, a major isoform of VGLUTs, is involved in TRPV1 activation-associated glutamate release during normal acute and inflammatory pain.

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

The present study investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain or trigeminal neuropathic pain. Experiments were carried out on male Sprague–Dawley rats weighing between 230 and 280 g. Under anesthesia, a polyethylene tube was implanted in the atlanto-occipital membrane for intracisternal administration. IL-1β-induced inflammation was employed as an orofacial acute inflammatory pain model. IL-1β (10 ng) was injected subcutaneously into one vibrissal pad. We used the trigeminal neuropathic pain animal model produced by chronic constriction injury of the infraorbital nerve. DL-threo-β -benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block the spinal glutamate transporter and the glutamine synthetase activity in astroglia. Intracisternal administration of TBOA produced mechanical allodynia in naïve rats, but it significantly attenuated mechanical allodynia in rats with interleukin (IL)-1 β-induced inflammatory pain or trigeminal neuropathic pain. In contrast, intracisternal injection of MSO produced antiallodynic effects in rats treated with IL-1β or with infraorbital nerve injury. Intracisternal administration of MSO did not produce mechanical allodynia in naive rats. These results suggest that blockade of glutamate recycling induced pro-nociception in naïve rats, but it paradoxically resulted in anti-nociception in rats experiencing inflammatory or neuropathic pain. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic pain conditions.

The ultrastructural parameters related to synaptic release of endings which are presynaptic to tooth pulp afferent terminals (p-endings) were analyzed to understand the underlying mechanism for presynaptic modulation of tooth pulp afferents. Tooth pulp afferents were labelled by applying wheat-germ agglutinin conjugated horseradish peroxidase to the rat right lower incisor, whereafter electron microscopic morphometric analysis with serial section and reconstruction of p-endings in the trigeminal oral nucleus was performed. The results obtained from 15 p-endings presynaptic to 11 labeled tooth pulp afferent terminals were as follows. P-endings contained pleomorphic vesicles and made symmetrical synaptic contacts with labeled terminals. The p-endings showed small synaptic release-related ultrastructural parameters: volume, 0.82 ± 0.45 μm3 (mean ± SD); surface area, 4.50 ± 1.76 μm2; mitochondrial volume, 0.15 ± 0.07 μm3; total apposed surface area, 0.69 ± 0.24 μm2; active zone area, 0.10 ± 0.04 μm2; total vesicle number, 1045 ± 668.86; and vesicle density, 1677 ± 684/μm2. The volume of the p-endings showed strong positive correlation with the following parameters: surface area (r=0.97, P<0.01), mitochondrial volume (r=0.56, P<0.05), and total vesicle number (r=0.73, P<0.05). However, the volume of p-endings did not positively correlate or was very weakly correlated with the apposed surface area (r=-0.12, P=0.675) and active zone area (r=0.46, P=0.084). These results show that some synaptic release-related ultrastructural parameters of p-endings on the tooth pulp afferent terminals follow the “size principle” of Pierce and Mendell (1993) in the trigeminal nucleus oralis, but other parameters do not. Our findings may demonstrate a characteristic feature of synaptic release associated with p-endings.

Previous studies suggested that myelinated axons innervating rat molar pulps undergo morphological changes in their peripheral course. However, little information is available on the morphological feature of the parent axons at the site of origin. We therefore investigated the size of the myelinated parent axons and their morphological features at the proximal sensory root of the trigeminal ganglion by horseradish peroxidase (HRP) injection into rat upper molar pulps and subsequent light and electron microscopy. A total of 248 HRP-labeled myelinated axons investigated were highly variable in the size. Fiber area, fiber diameter, axon area (axoplasm area), axon diameter (axoplasm diameter), and myelin thickness were 11.32 ± 8.36 μm2 (0.80~53.17 μm2), 3.99 ± 1.53 μm (1.08~9.26 μm), 8.70 ± 6.30 μm2 (0.70~41.83 μm2), 3.13 ± 1.13 μm (0.94~7.20 μm) and 0.43 ± 0.23 μm (0.07~1.06 μm), respectively. The g-ratio (axon diameter / fiber diameter) of the labeled axons was 0.79 ± 0.05 (0.61~0.91). Axon diameter was highly correlated with myelin thickness (correlation coefficients, r=0.83) but little correlated with g-ratio (r=−0.33) of individual myelinated parent axons. These results indicate that myelin thickness of the myelinated parent axons innervating rat molar pulps increase with increasing axon diameter, thus maintaining a constant g-ratio.

Growing evidence suggests that mitochondrial reactive oxygen species (ROS) are involved in various pain states. This study was performed to investigate whether ROS-induced changes in neuronal excitability in trigeminal subnucleus caudalis are related to ROS generation in mitochondria. Confocal scanning laser microscopy was used to measure ROS-induced fluorescence intensity in live rat trigeminal caudalis slices. The ROS level increased during the perfusion of malate, a mitochondrial substrate, after loading of 2′,7′-dichlorofluorescin diacetate (H2DCF-DA), an indicator of the intracellular ROS; the ROS level recovered to the control condition after washout. When pre-treated with phenyl N-tert-butylnitrone (PBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL), malate-induced increase of ROS level was suppressed. To identify the direct relation between elevated ROS levels and mitochondria, we applied the malate after double-loading of H2DCF-DA and chloromethyl-X-rosamine (CMXRos; MitoTracker Red), which is a mitochondria- specific fluorescent probe. As a result, increase of both intracellular ROS and mitochondrial ROS were observed simultaneously. This study demonstrated that elevated ROS in trigeminal subnucleus caudalis neuron can be induced through mitochondrial-ROS pathway, primarily by the leakage of ROS from the mitochondrial electron transport chain.

목 적 : 삼차신경통은 심한 전기적 통증, 전 격통이 삼차신경 분지 중 하나 혹은 그 이상의 영역에 걸쳐 나타나는 안면통증 증후군이다. 삼차신경통의 발생기전은 정확히 알려져 있지 않으나 대부분의 경우 특별한 원인을 찾을 수 없는 특발형이다. 이에 본 연구에서는 삼차신경통 환자의 진단에 있어 중요한 Protocol인 3D VISTA와 3D SPACE를 비교하여 진단적 가치에 도움이 되는 Sequence를 알아보고자 하였다. 대상 및 방법 : 2013년10월 1일부터 12월 30일까지 본원에서 검사한 환자 20명을 대상으로 조사하였다. 남성9명, 여성 11명 이었으며 평균 연령은 52세였다. 검사에 사용된 장비는 3.0T 자기공명 영상 장비(Siemens skyra, Phillips Ingenia)를 이용하여 cranial nerve를 검사하였다. 사용된 Siemens skyra 3D SPACE 매개변수로는 TR/TE:1190/203ms, matrix: 320×320, Slice thickness: 0.5mm, Flip angle: 135, slice/slab: 112, voxel size: 0.28×0.28×0.5를 이용하였다. Phillips Ingenia 3D VISTA 매개변수로는 TR/TE: 2000/200ms, matrix: 320×320, Slice thickness: 0.6mm, Flip angle:90°, slice/slab: 100, voxel size:0.6×0.6×0.6 를 이용하여 영상을 획득하였다. 평가방법은 정량적 분석과 정성적 분석을 통해 영상을 분석하였으며, 정량적 분석은 trigeminal nerve와 Cerebellum에 ROI를 신호 대 잡음비(SNR)와 대조도 대 잡음비(CNR)를 측정하였다, 정성적 분석은 3D VISTA와 3D SPACE의 영상으로 해부학적 구조의 명확도와 전반적인 영상의 평가를 방사선사 3명 전문의2명에게 의뢰하여 정성적 분석을 하였다. 결 과 : 정략적 분석한 결과 3D VISTA 와 3D SPACE 평균 신호대 잡음비는 trigeminal nerve right/left 173.01/213.47평균 신호대 잡음비는193.24로 측정되었고, 3D SPACE의 trigeminal nerve right/left 99.61/130.83 평균 신호대 잡음비는115.22로 측정되었고, Cerebellum 137.32/58.06으로 측정되었다. 3D VISTA 와 3D SPACE sequence의 trigeminal nerve와 Cerebellum의 평균 대조도 대 잡음비는 114.74/120.18로 측정 되었다(p<0.05). 정성적 분석으로는 trigeminal nerve와 Cerebellum의 영상을 영상의학과 판독의 1명, 신경과 전문의 1명 방사선사 3명에게 의뢰하여 인공물 발생 정도, 해부학적 구조의 명확도, 영상선명도 및 전체적인 영상의 질을 평가한 결과 3D VISTA와 3D SPACE 영상이 4.3/4.1로 측정되었다(p<0.05). 결 론 : 고자장의 MRI 장비의 개발과 보급, 새로운 검사기법의 개발로 인해 현재 측두골과 같은 미세한 구조물이 주를 이루는 부위의 검사에서 MRI검사의 진단적 가치와 효용성은 다른 검사에 비해 탁월하여 질병의 확진과 치료 과정에서의 예후 등을 평가할 수 있기에 임상적 가치가 매우 높다고 평가받고 있다. 3TMR 장비에서 사용하는 sequence 중 T2 강조영상을 대표하는 3D VISTA와 3D SPACE를 비교해본 결과 3D VISTA sequence가 SNR이 높게 측정이 되었으나 CNR을 비교해 보면 SPACE sequence가 높게 측정 되었다. 두 가지 매개변수에서 정량, 정성 평가는 큰 차이를 보이지는 않고 있다. 따라서 정확한 판독을 위하여 DWI, Post 3D FLAIR 을 추가하여 사용한다면 진단에 유용하리라 사료된다.

Various voltage-gated K+ currents were recently described in dorsal root ganglion (DRG) neurons. However, the characterization and diversity of voltage-gated K+ currents have not been well studied in trigeminal root ganglion (TRG) neurons, which are similar to the DRG neurons in terms of physiological roles and anatomy. This study was aimed to investigate the characteristics and diversity of voltage-gated K+ currents in acutely isolated TRG neurons of rat using whole cell patch clamp techniques. The first type (type I) had a rapid, transient outward current (IA) with the largest current size having a slow inactivation rate and a sustained delayed rectifier outward current (IK) that was small in size having a fast inactivation rate. The IA currents of this type were mostly blocked by TEA and 4-AP, K channel blockers whereas the IK current was inhibited by TEA but not by 4-AP. The second type had a large IA current with a slow inactivation rate and a medium size-sustained delayed IK current with a slow inactivation rate. In this second type (type II), the sensitivities of the IA or IK current by TEA and 4-AP were similar to those of the type I. The third type (type III) had a medium sized IA current with a fast inactivation rate and a large sustained IK current with the slow inactivation rate. In type III current, TEA decreased both IA and IK but 4-AP only blocked IA current. The fourth type (type IV) had a smallest IA with a fast inactivation rate and a large IK current with a slow inactivation rate. TEA or 4-AP similarly decreased the IA but the IK was only blocked by 4-AP. These findings suggest that at least four different voltage-gated K+ currents in biophysical and pharmacological properties exist in the TRG neurons of rats.

The deleted in colorectal cancer (DCC) protein mediates attractant responses to netrin during axonogenesis. In the rat trigeminal ganglia (TG), axons must extend toward and grow into the trigeminal nerve to innervate target tissues such as dental pulp. Our present study aimed to investigate the exp- ression of DCC in the TG. Four developmental timepoints were assessed in the experiments: postnatal days 0, 7 and 10 and adulthood. RT-PCR and western blotting revealed that the expression of DCC mRNA and protein does not signi- ficantly change throughout development. Immunohistoche- mistry demonstrated that DCC expression in the TG was detectable in the perikarya region of the ganglion cells du- ring development. Nerve injury at 3 and 5 days after the man- dibular nerve had been cut did not induce altered expression of DCC mRNA in the TG. Moreover, DCC-positive cell bodies also showed similar immunoreactive patterns after a nerve cut injury. The results of this study suggest that DCC constituti- vely participates in an axonogenesis attractant in ways other than expression regulation.

Previous clinical studies have demonstrated that gabapentin, a drug that binds to the voltage-gated calcium channel α2δ1 subunit proteins, is effective in the management of neuropathic pain, but there is limited evidence that addresses the participation of glial cells in the antiallodynic effects of this drug. The present study investigated the participation of glial cells in the anti-nociceptive effects of gabapentin in rats with trigeminal neuropathic pain produced by mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to induce injury to the inferior alveolar nerve. Mal-positioned dental implants significantly decreased the air-puff thresholds both ipsilateral and contralateral to the injury site. Gabapentin was administered intracisternally beginning on postoperative day (POD) 1 or on POD 7 for three days. Early or late treatment with 0.3, 3, or 30 μg of gabapentin produced significant anti-allodynic effect in the rats with mal-positioned dental implants. On POD 9, in the mal-positioned dental implants group, OX-42, a microglia marker, and GFAP, an astrocyte marker, were found to be up-regulated in the medullary dorsal horn, compared with the naive group. However, the intracisternal administration of gabapentin (30 μg) failed to reduce the number of activated microglia or astrocytes in the medullary dorsal horn. These findings suggest that gabapentin produces significant antinociceptive effects, which are not mediated by the inhibition of glial cell function in the medullary dorsal horn, in a rat model of trigeminal neuropathic pain.

LAR-RPTP (leukocyte common antigen-related receptor protein tyrosine phosphatase) is an important regulator in the nervous system, but little is known about its expression pattern in rat trigeminal ganglion (TG) neurons. To examine whether LAR-RPTP is expressed in the TG in the current study, we sacrificed rats at 0, 7, 10 and 56 day postpartum (dpp) and a second group of rats at 3 and 5 days after an experimental tooth extraction as a TG injury model. RT-PCR was then used to determine the level of LAR-RPTP expression in the TG and immunohistology was employed to detect the subcellular localization of the protein. The mRNA expression of LAR-RPTP during the developmental stages in the TG was found to gradually increase. After experimental tooth extraction however, these transcript levels had significantly decreased at three days. LAR-RPTP protein signals in the TG were found to be cytoplasmic in the normal animals but interestingly, at five days after an experimental tooth extraction, these signals were rare. These results indicate that LAR-RPTP may be regulated during both the developmental as well as regenerative processes that take place in the TG. This further suggests that LAR-RPTP is not only involved in primary axonogenesis but possibly also in the molecular control of axons during TG repair.

Epithelioid hemangioma is an unusual, which was at first described as angiolymphoid hyperplasia with eosinophilia (ALHE) in 1969 and misinterpreted as the same disease with Kimura’s disease. But now it represents a distinctive vascular tumor, a different entity with those inflammatory conditions. Here, we present a case of epithelioid hemangioma appearing as a diffuse gingival nodular mass in 33‐year‐old male who had suffered from the idiopathic sharp pain of left mandible area previously and later extended to left maxillary region, therefore the gingival lesion was clinically estimated as malignancy associated with neural invasion. CT images revealed the soft tissue mass restricted to left maxillary gingiva without infiltration to underlying maxillary alveolar bone. Histologically, the circumscribed soft tissue mass consist of solid sheets of epithelioid to spindled cells, expressing reactivity for neither cytokeratin AE1/3 nor HMB‐45, but for CD31, endothelial cell marker. Therefore, the lesion was pathologically diagnosed as epithelioid hemangioma. Diagnostic evaluation for the neurologic symptoms of the patient revealed the trigeminal neuralgia, accompanying with the present epithelioid hemangioma incidentally. Awareness of epithelioid hemangioma should be emphasized not to be misdiagnosed as malignant disease like an invasive squamous cell carcinoma, malignant melanoma, or angiosarcoma. Proper evaluation and interpretation for neural symptom may lead to the correct differential diagnosis and therapeutic intervention

The present study investigated the role of ERK in the onset of mechanical and cold allodynia in a rat model of compression of the trigeminal ganglion by examining changes in the air-puff thresholds and number of scratches following the intracisternal injection of PD98059, a MEK inhibitor. Male Sprague Dawley rats weighing between 250 and 260 g were used. Under anesthesia, the rats were mounted onto a stereotaxic frame and received 4% agar (10μℓ) solution to compress the trigeminal ganglion. In the control group, the animals were given a sham operation without the application of agar. Changes in behavior were examined at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Compression of the trigeminal ganglion significantly decreased the air-puff thresholds. Mechanical allodynia was established within 3 days and persisted over postoperative day 24. To evaluate cold allodynia, nociceptive scratching behavior was monitored after acetone application on the vibrissa pad of the rats. Compression of the trigeminal ganglion was found to produce significant cold allodynia, which persisted for more than 40 days after surgery. On postoperative day 14, the intracisternal administration of 1 μg or 10 μg of PD98059 in the rat model significantly decreased the air-puff thresholds on both the ipsilateral and contralateral side. The intracisternal administration of 10 μg of PD98059 also significantly alleviated the cold allodynia, compared with the vehicle-treated group. These results suggest that central ERK plays an important role in the development of mechanical and cold allodynia in rats with compression of the trigeminal ganglion and that a targeted blockade of this pathway is a potential future treatment strategy for trigeminal neuralgia-like nociception.

Somatostatin (SST) is a known neuromodulator of the central nervous system. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) receives many thinmyelinated Að-fiber and unmyelinated C primary afferent fibers and is involved in nociceptive processing. Many studies have demonstrated that SST plays a pivotal role in pain modulation in the spinal cord. However, little is yet known about the direct effects of SST on the SG neurons of the Vc in adult mice. In our present study, we investigated the direct membrane effects of SST and a type 2 SST receptor agonist, seglitide (SEG), on the SG neurons of the Vc using a gramicidin-perforated current clamp in adult mice. The majority (53%, n = 27/51) of the adult SG neurons were hyperpolarized by SST (300 nM) but no differences were found in the hyperpolarization response rate between males and females. When SST was applied successively, the second response was smaller (76±9.5%, n=19), suggesting that SST receptors are desensitized by repeated application. SST-induced hyperpolarization was also maintained under conditions where presynaptic events were blocked (75±1.0%, n=5), suggesting that this neuromodulator exerts direct effects upon postsynaptic SG neurons. SEG was further found to induce membrane hyperpolarization of the SG neurons of the Vc. These results collectively demonstrate that SST inhibits the SG neuronal activities of the Vc in adult mice with no gender bias, and that these effects are mediated via a type 2 SST receptor, suggesting that this is a potential target for orofacial pain modulation.

We recently described a novel animal model of trigeminal neuropathic pain following compression of the trigeminal ganglion (Ahn et al., 2009). In our present study, we adapted this model using male Sprague-Dawley rats weighing between 250-260 g and then analyzed the behavioral responses of these animals following modified chronic compression of the trigeminal ganglion. Under anesthesia, the rats were mounted onto a stereotaxic frame and a 4% agar solution (10μL) was injected in each case on the dorsal surface of the trigeminal ganglion to achieve compression without causing injury. In the control group, the rats received a sham operation without agar injection. Air-puff, acetone, and heat tests were performed at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after surgery. Compression of the trigeminal ganglion produced nociceptive behavior in the trigeminal territory. Mechanical allodynia was established within 3 days and recovered to preoperative levels at approximately 60 days following compression. Mechanical hyperalgesia was also observed at 7 days after compression and persisted until the postoperative day 40. Cold hypersensitivity was established within 3 days after compression and lasted beyond postoperative day 55. In contrast, compression of the trigeminal ganglion did not produce any significant thermal hypersensitivity when compared with the sham operated group. These findings suggest that compression of the trigeminal ganglion without any injury produces prolonged nociceptive behavior and that our rat model is a useful system for further analysis of trigeminal neuralgia.

Bicuculline is one of the most commonly used GABAд eceptor antagonists in electrophysiological research. Because of its poor water solubility, bicuculline quaternary ammonium salts such as bicuculline methiodide (BMI) and bicuculline methbromide are preferred. However, a number of studies have shown that BMI has non-GABAд eceptor-mediated effects. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is implicated in the processing of nociceptive signaling. In this study, we investigated whether BMI has non-GABA receptor-mediated activity in Vc SG neurons using a whole cell patch clamp technique. SG neurons were depolarized by application of BMI (20M) using a high Cℓ⁻ipette solution. GABA ( 30-100μM) also induced membrane depolarization of SG neuron. Although BMI is known to be a GABAд receptor antagonist, GABA-induced membrane depolarization was enhanced by co-application with BMI. However, free base bicuculline (fBIC) and picrotoxin (PTX), a GABAд and GABAс receptor antagonist, blocked the GABA-induced response. Furthermore, BMI-induced membrane depolarization persisted in the presence of PTX or an antagonist cocktail consisting of tetrodotoxin (Nα+ nnel blocker),AP-5 (NMDA receptor antagonist), CNQX (non-NMDA receptor antagonist), and strychnine (glycine receptor antagonist). Thus BMI induces membrane depolarization by directly acting on postsynaptic Vc SG neurons in a manner which is independent of GABAд receptors. These results suggest that other unknown mechanisms may be involved in BMI-induced membrane depolarization.

The present study investigated inflammatory hypersensitivity following compression of the trigeminal ganglion in rats. Experiments were carried out on male Sprague-Dawley rats weighing 250-260 g. Under anesthesia, rats were mounted on a stereotaxic frame and injected with 8μL of 4% agar solution through a stainless steel injector to compress the trigeminal ganglion. In the control group, rats underwent a sham operation without agar injection. Injection sites were examined with a light micrograph after compression of the trigeminal ganglion. Air-puff thresholds (mechanical allodynia) were evaluated 3 days before surgery and 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Air-puff thresholds significantly decreased after compression of the trigeminal ganglion. Mechanical allodynia was established within 3 days and remained strong over 24 days, returning to preoperative levels approximately 40 days following compression. After subcutaneous injection of 5% formalin (50μL) in the compression of the trigeminal ganglion-treated rats, nociceptive scratching behavior was recorded for 9 successive 5-min internals. Injection of formalin into the vibrissa pad significantly increased the number of scratches and duration of noxious behavioral responses in sham-treated rats. Noxious behavioral responses induced by subcutaneous formalin administration were significantly potentiated in rats with trigeminal ganglion compression. These findings suggest that compression of the trigeminal ganglion enhanced formalin-induced infla-mmatory pain in the orofacial area.

In the primary sensory neuron of the mesencephalic trigeminal nucleus (MTN), the peripheral axon supplies a large number of annulospiral endings surrounding intrafusal fibers encapsulated in single muscle spindles while the central axon sends only a few number of synapses onto single α-motoneuron₃.(α-MN₃)Therefore, the α-y linkage is thought to be very crucial in the jaw-closing movement. Spike activity in a y-motoneuron (y-MN) would induce a large number of impulses in single peripheral axons by activating many intrafusal fibers simultaneously, subsequently causing an activation of α-MN₃ in spite of the small number of synapses. Thus, the activity of y-MN₃ may be vital for modulation of jaw-closing movements. Independently of such a spindle activity modulated by y-MN₃, somatic depolarization in MTN neurons is known to trigger the oscillatory spike activity. Nevertheless, the trafficking of these spikes arising from the two distinct sources of MTN neurons is not well understood. In this short review, switching among multiple functional modes of MTN neurons is discussed. Subsequently, it will be discussed which mode can support the α-y linkage. In our most recent study, simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-back-propagation from the spike-initiation site in the stem axon to the soma in response to a somatic current pulse. The persistent Nα+ current was found to be responsible for the spike-initiation in the stem axon, the activation threshold of which was lower than those of soma spikes. Somatic inputs or impulses arising from the sensory ending, whichever trigger spikes in the stem axon first, would be forwarded through the central axon to the target synapse. We also demonstrated that at hyperpolarized membrane potentials, 4-AP-sensitive K+ current (IK₄_AP) exerts two opposing effects on spikes depending on their origins; the suppression of spike initiation by increasing the apparent electrotonic distance between the soma and the spike-initiation site, and the facilitation of axonal spike invasion at higher frequencies by decreasing the spike duration and the refractory period. Through this mechanism, the spindle activity caused by y-MN₃would be safely forwarded to α-MN. Thus, soma spikes shaped differentially by this IK₄_AP depending on their origins would reflect which one of the two inputs was forwarded to the target synapses.

R-type(Cav2.3) calcium channel contributes to pain sensation in peripheral sensory neurons. Six isoforms of Cav2.3 that result from combinations of presence or deletion of three inserts(insert I and insert in the II-III loop, and insert III in N-terminal regions) have been demonstrated to be present in different mammalian tissues. However, the molecular basis of Cav2.3 in trigeminal ganglion(TG) neurons is not known. In the present study, we determined which isoforms of Cav2.3 are expressed in rat TG neurons using the RT-PCR analysis. Whole tissue RT-PCR analyses revealed that only two isoforms, Cav2.3a and Cav2.3e, were present in TG neurons. From single-cell RT-PCR, we found that Cav2.3e rather than Cav2.3a was the major isoform expressed in TG neurons, and Cav2.3e was preferentially detected in small-sized neurons that express nociceptive marker, transient receptor potential vanilloid 1(TRPV1). Our results suggest that Cav2.3e in trigeminal neurons may be a potential target for the pain treatment.

The mesencephalic trigeminal nucleus (Mes V) contains cell bodies of primary afferent sensory neurons that relay proprioceptive information from the periodontium and masticatory muscles and function as typical sensory neurons or potentially as integrative interneurons. In the present study, we studied these two potential functions using combined experimental approaches of retrograde labeling and whole cell patch clamp recording. Mes V neurons that presumably originate from periodontal nerve fibers in subsets of Mes V nucleus were identified by retrograde labeling with a fluorescent dye, DiI, which was applied onto inferior alveolar nerve. These cells were elliptical perikarya shaped cells about 40μmin diameter. In these neurons, we measured high voltage-activated calcium channel (HVACC) currents GABAв agonist, baclofen, inhibited calcium currents, and the HVACC currents inhibition by baclofen was voltage-dependent, exhibited prepulse facilitation, indicating that it was mediated by Gi/Go protein. Taken together, our results demonstrate that Mes V neurons not only have cell bodies originating from periodontium, but also receive synaptic inputs including GABAergic neurons suggesting that Mes V neurons function as both primary sensory neurons and integrative interneurons.