BACKGROUND: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. METHODS: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. RESULTS: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). CONCLUSIONS: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.
Animals ; Brain-Derived Neurotrophic Factor ; Capsaicin ; Cyclooxygenase 2 ; Facial Pain ; Fluorescent Antibody Technique ; Injections, Subcutaneous ; Lip ; Microinjections ; Nociceptors ; Orexin Receptor Antagonists ; Orexins ; Pain Measurement ; Pain Perception ; Rats ; Trigeminal Caudal Nucleus ; Trigeminal Neuralgia ; Trigeminal Nuclei

Polyacrylamide hydrogel is a widely used filler material in cosmetic procedures performed on the face and breasts. Recently, however, complications including inflammation, deformity, and pain have been reported. The present article addresses unregulated materials/products injected as dermal fillers. The authors report a case involving a 29-year-old woman who developed severe facial pain after undergoing a cosmetic procedure with injectable triamcinolone and hyaluronidase. Two months later, the pain spread to her upper and lower limbs, and abdomen, which eventually led to the the development and diagnosis of complex regional pain syndrome (CRPS) in the upper limbs. The authors hypothesize that CRPS in the upper limbs was responsible for the facial pain through sensitization of third-order neurons and the trigeminal nucleus caudalis extending to the upper cervical segments.
Abdomen ; Adult ; Breast ; Congenital Abnormalities ; Dermal Fillers ; Diagnosis ; Facial Neuralgia ; Facial Pain* ; Female ; Humans ; Hyaluronic Acid ; Hyaluronoglucosaminidase ; Hydrogel ; Inflammation ; Lower Extremity ; Neurons ; Triamcinolone ; Trigeminal Nuclei ; Upper Extremity*

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.
Animals ; Horseradish Peroxidase ; Incisor ; Mitochondrial Size ; Rats ; Tooth* ; Trigeminal Nuclei

Migraine headache is commonly associated with signs of exaggerated intracranial and extracranial mechanical sensitivities. Patients exhibiting signs of intracranial hypersensitivity testify that their headache throbs and that mundane physical activities that increase intracranial pressure (such as bending over or coughing) intensify the pain. Patients exhibiting signs of extracranial hypersensitivity testify that during migraine their facial skin hurts in response to otherwise innocuous activities such as combing, shaving, letting water run over their face in the shower, or wearing glasses or earrings (termed here cephalic cutaneous allodynia). Such patients often testify that during migraine their bodily skin is hypersensitive and that wearing tight cloth, bracelets, rings, necklaces and socks or using a heavy blanket can be uncomfortable and/or painful (termed her extracephalic cutaneous allodynia). This review summarizes the evidence that support the view that activation of the trigeminovascular pathway contribute to the headache phase of a migraine attack, that the development of throbbing in the initial phase of migraine is mediated by sensitization of peripheral trigeminovascular neurons that innervate the meninges, that the development of cephalic allodynia is propelled by sensitization of second-order trigeminovascular neurons in the spinal trigeminal nucleus which receive converging sensory input from the meninges as well as from the scalp and facial skin, and that the development of extracephalic allodynia is mediated by sensitization of third-order trigeminovascular neurons in the posterior thalamic nuclei which receive converging sensory input from the meninges, facial and body skin.
Animals ; Comb and Wattles ; Ear ; Eyeglasses ; Glass ; Headache ; Humans ; Hyperalgesia ; Hypersensitivity ; Intracranial Pressure ; Linear Energy Transfer ; Meninges ; Migraine Disorders ; Motor Activity ; Neurons ; Posterior Thalamic Nuclei ; Scalp ; Skin ; Thalamus ; Trigeminal Nucleus, Spinal ; Tryptamines ; Water

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicin-induced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.
Animals ; Capsaicin ; Headache ; Migraine Disorders ; Models, Animal ; N-Methylaspartate ; Neurons ; Phosphorylation ; Rats ; Receptors, sigma ; Trigeminal Nuclei

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.
Animals ; Cell Membrane ; Central Nervous System ; Cyclic N-Oxides ; Diffusion ; Facial Pain ; Formaldehyde ; Guanylate Cyclase ; Horns ; Imidazoles ; Indoles ; Maleimides ; Neurons ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Nociception ; Pain Measurement ; Protein Kinase C ; Rats ; Spinal Cord ; Trigeminal Nuclei

In the present study, we performed immunohistochemical studies to investigate the detailed distribution of insulin-like growth factor binding protein 7 (IGFBP7) in the central nervous system of adult rats. Twelve adult (4~6 month old) Sprague-Dawley rats were examined in this study. Immunohistochemistry using specific antibodies against IGFBP7 was performed in accordance with the free-floating method. In the present study, IGFBP7 immunoreactivity was observed in the cerebral cortex, hippocampus, brainstem, cerebellum and spinal cord. In the cerebral cortex, heavily stained neurons were seen in layers II-VI. In the hippocampus, pyramidal cells in CA1-3 region were strongly immunoreactive for IGFBP7. Strong immunoreactive neurons were also found in the supraoptic nucleus, paraventricular nucleus, periaqueductal gray and oculomotor nucleus. In the cerebellum, IGFBP7 immunoreactivity was prominent in the Purkinje cells and cerebellar output neurons. IGFBP7-immunoreactive neurons were prominent in the superior vestibular nucleus, cochlear nucleus, trigeminal motor nucleus, nucleus of the trapezoid, and facial nucleus. IGFBP7-immunoreactive neurons were also observed mainly in the anterior horn of the spinal cord. The first demonstration of IGFBP7 localization in the whole brain may provide useful data for the future investigations on the structural and functional properties of IGFBP7.
Adult ; Animals ; Antibodies ; Brain ; Brain Stem ; Carrier Proteins ; Central Nervous System ; Cerebellum ; Cerebral Cortex ; Cochlear Nucleus ; Hippocampus ; Horns ; Humans ; Immunohistochemistry ; Neurons ; Paraventricular Hypothalamic Nucleus ; Periaqueductal Gray ; Purkinje Cells ; Pyramidal Cells ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Supraoptic Nucleus ; Trigeminal Nuclei

The interstitial nucleus of the spinal trigeminal tract (INV) contains many calbindin-D28k-containing neurons (CB-neurons) receiving convergence information from the somatic and visceral structures. The purpose of the present study was to confirm whether the primary afferent terminals from the inferior alveolar nerve (IAN) make close contact and synaptic connections with the same CB-neurons receiving visceral nociceptive signals in INV. Biotinylated dextran amine (BDA) and horseradish peroxidase (HRP) tracing combined with CB and Fos proteins immunohistochemistry were used. After injections of BDA and formalin into unilateral IAN and upper alimentary tract, respectively, the transganglionic labeled afferent fibers and terminals from IAN were observed in the ipsilateral INV, especially in its enlarged part. A large number of CB- and Fos-like immunoreactive (LI) neurons were found in bilateral INV. These CB- and Fos-LI neurons mostly overlapped with BDA-labeled terminals in the enlarged part of INV. About one half of the CB-LI neurons were double labeled with Fos-LI nuclei (74/153). The terminals from IAN were to made close contacts with many CB/Fos-double labeled or CB-single labeled neurons. After injection of HRP into IAN, HRP-labeled fibers and terminals in INV were similar to that labeled with BDA. Under the electron microscope, a large number of CB-LI dendrites and a few soma in the enlarged part of INV were found to form asymmetrical axo-dendritic and axo-somal synapses with the HRP-labeled axon terminals. These results indicate that the orofacial somatic inputs from IAN and the visceral nociceptive inputs from the upper alimentary tract converge onto the same CB-containing neurons in INV. These CB-containing neurons in INV probably play an important role in information integration as well as visceral and cardiovascular activity.
Animals ; Calbindin 1 ; Calbindins ; Face ; innervation ; Male ; Microscopy, Confocal ; Neural Pathways ; cytology ; physiology ; Neurons ; physiology ; Nociceptors ; physiology ; Presynaptic Terminals ; physiology ; Proto-Oncogene Proteins c-fos ; physiology ; Rats ; Rats, Sprague-Dawley ; S100 Calcium Binding Protein G ; metabolism ; physiology ; Trigeminal Nuclei ; physiology ; Viscera ; innervation

The nerves innervating the sublingual gland of the rat was investigated using PRV (pseudorabies virus) as a neural tracer. The neural tracer was injected into left sublingual gland of the rat. In the central nervous system, PRV immunoreactive neurons were labeled bilaterally and tended to be more densely labeled in the left side. PRV immunoreactive neuronal cell bodies and fibers were observed in insular cortex, paraventricular nucleus, deep mesencephalic nucleus, spinal trigeminal tract, lateral paragigantocellular nucleus, parvicellular reticular nucleus, raphe obscurus, gigantocellular reticular nucleus and gigantocellular reticular nucleus, alpha. The more densely labeled PRV immunoreactive neurons were found in the deep mesencephalic nucleus, spinal trigeminal tract and lateral paragigantocellular nucleus. These results may provide a neuroanatomical data on the nerves innervating the sublingual gland in the rat brain.
Animals ; Brain* ; Central Nervous System ; Herpesvirus 1, Suid* ; Neurons ; Paraventricular Hypothalamic Nucleus ; Pseudorabies* ; Raphe Nuclei ; Rats* ; Sublingual Gland* ; Trigeminal Nucleus, Spinal

We used cholera toxin B subunit (CTB) as a neural tracer to localize motor neuronal cell bodies innervating the digastric muscle. After CTB injection into the left anterior belly, CTB-labelled motor neuronal cell bodies were found in caudal half of the left and right trigeminal nucleus, the left and right facial nucleus, the accessory facial nucleus and the accessory trigeminal nucleus in pons. The total number of CTB-labelled motor neuronal cell bodies were 1,179+/-119.5 in the left pons and 246+/-61.8 in the right pons after CTB injections into the left anterior belly of digastric muscle. After CTB injection into left posterior belly, CTB-labelled motor neuronal cell bodies were found only in the left ventral part of accessory facial nucleus in caudal pons and the total number of CTB-labelled motor neuronal cell bodies were 270+/-29.3.
Animals ; Cholera Toxin* ; Cholera* ; Motor Neurons* ; Pons ; Rats* ; Trigeminal Nuclei