It is well known that trigeminal nerve injury causes hyperexcitability in trigeminal ganglion neurons, which become sensitized. Long after trigeminal nerve damage, trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1/C2) nociceptive neurons become hyperactive and are sensitized, resulting in persistent orofacial pain. Communication between neurons and non-neuronal cells is believed to be involved in these mechanisms. In this article, the authors highlight several lines of evidence that neuron-glial cell and neuron macrophage communication have essential roles in persistent orofacial pain mechanisms associated with trigeminal nerve injury and/or orofacial inflammation.
Cell Communication ; Cervical Cord ; Facial Pain ; Inflammation ; Macrophages ; Neurons ; Nociceptors ; Trigeminal Ganglion ; Trigeminal Nerve ; Trigeminal Nerve Injuries ; Trigeminal Nucleus, Spinal

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

Acute peripheral facial palsy usually manifests Bell's palsy of unknown cause, and rarely lacunar infarct which located in facial nucleus can mimic peripheral facial palsy. A 73 year-old man with isolated facial asymmetry diagnosed with lacunar infarction which selectively involve the facial fascicles which lie in inferolateral aspect of pons. Clinicians should take into account the possibility of central lesion and brain stem infarction, even when patients present with isolated peripheral type facial palsy.
Bell Palsy ; Brain Stem Infarctions ; Facial Asymmetry ; Facial Nucleus ; Facial Paralysis* ; Humans ; Pons ; Stroke, Lacunar

The caudal subnucleus of the spinal trigeminal nucleus (medullary dorsal horn; MDH) receives direct inputs from small diameter primary afferent fibers that predominantly transmit nociceptive information in the orofacial region. Recent studies indicate that reactive oxygen species (ROS) is involved in persistent pain, primarily through spinal mechanisms. In this study, we aimed to investigate the role of xanthine/xanthine oxidase (X/XO) system, a known generator of superoxide anion (O₂(·−)), on membrane excitability in the rat MDH neurons. For this, we used patch clamp recording and confocal imaging. An application of X/XO (300 µM/30 mU) induced membrane depolarization and inward currents. When slices were pretreated with ROS scavengers, such as phenyl N-tert-butylnitrone (PBN), superoxide dismutase (SOD), and catalase, X/XO-induced responses decreased. Fluorescence intensity in the DCF-DA and DHE-loaded MDH cells increased on the application of X/XO. An anion channel blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), significantly decreased X/XO-induced depolarization. X/XO elicited an inward current associated with a linear current-voltage relationship that reversed near −40 mV. X/XO-induced depolarization reduced in the presence of La³⁺, a nonselective cation channel (NSCC) blocker, and by lowering the external sodium concentration, indicating that membrane depolarization and inward current are induced by influx of Na⁺ ions. In conclusion, X/XO-induced ROS modulate the membrane excitability of MDH neurons, which was related to the activation of NSCC.
Animals ; Catalase ; Facial Pain ; Fluorescence ; Ions ; Membranes ; Neurons* ; Oxidoreductases ; Posterior Horn Cells* ; Rats* ; Reactive Oxygen Species* ; Sodium ; Spinal Cord Dorsal Horn* ; Superoxide Dismutase ; Superoxides ; Trigeminal Nucleus, Spinal ; Xanthine Oxidase

BACKGROUND AND PURPOSE: During Vietnam War, many Korean soldiers were dispatched to fight in the war where they were exposed to Agent Orange. Until now, there exist only limited evidence on existence of association between exposure to Agent Orange and Parkinson's disease (PD). To elucidate the effects of Agent Orange exposure on PD, we compared the clinical characteristics and radiolabeled 18F-FP-CIT PET uptake between patients with Agent Orange exposure and patients with Agent Orange no-exposure. METHODS: We retrospectively evaluated 143 patients exposed to Agent Orange and 500 patients with no exposure to Agent Orange from our movement clinics database. The differences between clinical characteristics and pattern of 18F-FP-CIT PET uptake were investigated. RESULTS: Among Unified Parkinson's Disease Rating Scale III motor subscales, tremor at rest, rigidity, finger taps, and rapid alternating movement was significantly higher in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. The facial expression score was significantly lower in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. Compared to patients not exposed to Agent Orange, all basal ganglia areas (contra- and ipsilateral caudate nucleus, anterior putamen, and posterior putamen) showed a lower18F-FP-CIT uptake and higher asymmetry index of anterior and posterior putamen was found in patients exposed to Agent Orange. The caudate/putamen ratio was significantly lower in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. CONCLUSIONS: This study showed a different clinical profile and FP-CIT PET findings between patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. This finding suggests the possibility of different pathophysiology of PD in patients exposed to Agent Orange from idiopathic PD.
Basal Ganglia ; Caudate Nucleus ; Citrus sinensis* ; Facial Expression ; Fingers ; Humans ; Military Personnel ; Parkinson Disease* ; Putamen ; Retrospective Studies ; Tremor ; Vietnam

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.
Amygdala ; Autistic Disorder* ; Axons ; Brain ; Child ; Autism Spectrum Disorder* ; Cognition ; Deep Brain Stimulation ; Facial Expression ; Gestures ; Humans ; Limbic System ; Neurobiology ; Neuroimaging ; Nucleus Accumbens ; Reward ; Risk Factors ; Social Behavior

OBJECTIVETo evaluate the potential role of p38 mitogen-activated protein kinase (MAPK) in the orofacial inflammatory pain.

METHODSSD rats received subcutaneous injection of 2.5% formalin 50 µl in the left vibrissa pad to establish the inflammatory pain model. The rats were grouped into the control group, the formalin group (FOR group), the formalin + saline group (FOR + NS group) and the formalin + SB203580 group (FOR + SB group). SB203580 or saline was inserted into the rat's cisterna magna 20 minutes prior to the formalin injection, then the behavioral changes were tested. The immunofluorescence staining and Western blotting analysis were performed to examine c-fos, p38MAPK and phosphorylated p38 (p-p38) activity in Vc at 20, 60, 120, 180 minutes after formalin injection.

RESULTSp38MAPK was constitutively expressed in Vc (P > 0.05) and p38MAPK was activated following formalin injection.Compared with the control group at 20 min (0.12 ± 0.01), the level of p-p38 in FOR group (0.66 ± 0.04) and FOR + NS group (0.64 ± 0.04) increased significantly (P < 0.001). The expression of p-p38 peaked at 20 minutes, and then declined in each group. Intracisterna magna pretreatment of p38MAPK inhibitor SB203580 resulted in potent attenuation of phase II of pain behavior (P < 0.05), while the expression of c-fos was also inhibited, especially at the point of 120 min (P < 0.01).

CONCLUSIONSActivation of p38 mitogen-activated protein kinase played a major role in the development of orofacial inflammatory pain and it was verified by the experimental result that p38MAPK inhibitor SB203580 inhibited the formalin-induced orofacial pain.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Behavior, Animal ; Enzyme Inhibitors ; pharmacology ; Facial Pain ; chemically induced ; metabolism ; Formaldehyde ; Imidazoles ; pharmacology ; Male ; Phosphorylation ; Proto-Oncogene Proteins c-fos ; metabolism ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Trigeminal Caudal Nucleus ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVEPPTA and c-fos mRNA expression were detected in dog caudalis subnucleus of trigeminal spinal tract nucleus (VC) induced by trauma occlusion in order to investigate orofacial pain mechanism.

METHODSThe occlusal surface of the first and second maxillary right molars in 15 dogs were unilaterally raised 1.5 mm with casting Ni-Cr inlay which were fixed in Class I hole. On days 3, 7, 14, 30 and 60 after teeth operation, the VC of right and left sides were removed. PPTA and c-fos mRNAs were detected in experimental and control groups with reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS(1) The basal levels of PPTA and c-fos mRNAs were extremely low and poorly detectable in VC in control animals. (2) The expression of PPTA mRNA in VC of traumatic side was up regulated from 3 days after inlay was fixed in molar and reached peak level during 14 to 30 days and then down-regulated gradually and no significant difference was noted between 60 days group and control group. (3) c-fos mRNA expression was more intense during 3 to 7 days compared with the control group but undetectable in the other experimental period. (4) Both PPTA and c-fos mRNAs expression in VC of trauma occlusal side were more intense than that in the contralateral side.

CONCLUSIONSThe present results show that both PPTA and c-fos mRNA expression are elevated in dog's VC induced by traumatic occlusion. The primary afferent terminal of orofacial area is sensitized, which suggest one kind of mechanism of orofacial pain in the condition of traumatic occlusion.

Animals ; Dental Occlusion, Traumatic ; physiopathology ; Dogs ; Facial Neuralgia ; etiology ; Protein Precursors ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-fos ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; Tachykinins ; biosynthesis ; genetics ; Trigeminal Nucleus, Spinal ; metabolism

The generally accepted taste pathway in an animal projects ipsilaterally from the solitary nucleus. However, the path-way of gustatory fibers in the human brainstem has not been sufficiently clarified. A 57-year-old hypertensive man was admitted with sudden dizziness and hemiageusia. A neurological examination revealed also a diminution of taste on the left half of his tongue. A MRI showed a high signal intensity in the right lower pontine area. This case suggests that the unilateral lesion of the pons may lead to contralateral taste disturbances.
Ageusia ; Animals ; Brain Stem ; Cerebral Infarction ; Dizziness ; Facial Nerve ; Humans ; Infarction* ; Magnetic Resonance Imaging ; Middle Aged ; Neurologic Examination ; Pons ; Solitary Nucleus ; Tongue

BACKGROUND AND OBJECTIVES: The transsynaptic transfer of neurotropic viruses is an effective tool for tracing chains of connected neurons, because replication of virus in the recipient neurons after the transfer amplifies the "tracer signal". The aim of this study is to identify the central neural pathways projecting to the facial nerve using the Bartha strain of the Pseudorabies virus (PRV-Ba )as a transsynaptic tracer. MATERIALS AND METHODS: PRV-Ba was injected into the facial nerve in the stylomastoid foramen of a rat, and was localized in the rat brain with light microscopic immunohistochemistry using primary antibodies against the PRV-Ba. Sequential tracing was carried out on the retrogradely labeled neurons were done. RESULTS: The shapes of upper motor neurons of facial nerve were mostly ovoid or polygonal. The positive immunoreactive cells observed in the brainstem nuclei included raphe obscurus nucleus, facial nucleus, parvocellular reticular nucleus, spinal trigeminal nucleus, ventral parabrachial nucleus, central gray, and dorsal raphe nucleus. Other positive cells stained in the diencephalon were found in periventricular hypothalamic nucleus, dorsal hypothalamic area, orbital gyri, and infralimbic cortex in the frontal lobe. CONCLUSIONS: These results show the central neural pathways of facial nerve using PRV-Ba.
Animals ; Antibodies ; Brain ; Brain Stem ; Diencephalon ; Facial Nerve ; Frontal Lobe ; Herpesvirus 1, Suid ; Immunohistochemistry ; Motor Neurons ; Neural Pathways* ; Neurons ; Orbit ; Raphe Nuclei ; Rats ; Trigeminal Nucleus, Spinal