Orofacial anti-hypernociceptive effect of citral in acute and persistent inflammatory models in rats.

Orofacial pain has significant psychological and physiological effects. Citral (3,7-dimethyl-2,6-octadienal) is the main component of Cymbopogon citratus (DC) Stapf, an herb with analgesic properties. Although citral has been considered a potent analgesic, its putative effects on orofacial pain are still unknown. OBJECTIVE: The objective of this study is to test the hypothesis that citral modulates orofacial pain using two experimental models: formalin-induced hyperalgesia in the vibrissae area and during persistent temporomandibular hypernociception using Complete Freund's Adjuvant - CFA test. METHODS: For the formalin test, citral (100 and 300 mg/kg, oral gavage) or its vehicle (Tween 80, 1 %) were given 1 h before the formalin injection subcutaneously (sc) into the vibrissae area. For the CFA model, we analyzed the prophylactic (100 mg/kg of citral by oral gavage, 1 h before CFA injection) and the chronic therapeutic (citral treatment 1-hour post-CFA injection and daily post-CFA injection) effect of citral or its vehicle in animals treated with CFA for 8 days. RESULTS: Citral caused a decrease in formalin-induced local inflammation and the time spent performing nociceptive behavior in a dose-dependent fashion. Similarly, prophylactic and therapeutic citral treatment decreased the CFA-induced persistent mechanical hypernociception in the temporomandibular area. CONCLUSION: Our data strengthen the notion that citral plays a powerful antinociceptive role by decreasing orofacial hypernociception in formalin and CFA models.

A canonical interlaminar circuit in the sensory dorsal ventricular ridge of birds: The anatomical organization of the trigeminal pallium.

The dorsal ventricular ridge (DVR), which is the largest component of the avian pallium, contains discrete partitions receiving tectovisual, auditory, and trigeminal ascending projections. Recent studies have shown that the auditory and the tectovisual regions can be regarded as complexes composed of three highly interconnected layers: an internal senso-recipient one, an intermediate afferent/efferent one, and a more external re-entrant one. Cells located in homotopic positions in each of these layers are reciprocally linked by an interlaminar loop of axonal processes, forming columnar-like local circuits. Whether this type of organization also extends to the trigemino-recipient DVR is, at present, not known. This question is of interest, since afferents forming this sensory pathway, exceptional among amniotes, are not thalamic but rhombencephalic in origin. We investigated this question by placing minute injections of neural tracers into selected locations of vital slices of the chicken telencephalon. We found that neurons of the trigemino-recipient nucleus basorostralis pallii (Bas) establish reciprocal, columnar and homotopical projections with cells located in the overlying ventral mesopallium (MV). "Column-forming" axons originated in B and MV terminate also in the intermediate strip, the fronto-trigeminal nidopallium (NFT), in a restricted manner. We also found that the NFT and an internal partition of B originate substantial, coarse-topographic projections to the underlying portion of the lateral striatum. We conclude that all sensory areas of the DVR are organized according to a common neuroarchitectonic motif, which bears a striking resemblance to that of the radial/laminar intrinsic circuits of the sensory cortices of mammals.

Mechanisms involved in facial heat hyperalgesia induced by endothelin-1 in female rats.

OBJECTIVE: Pronociceptive responses to endothelins in the trigeminal system seem to be mediated by ETA and ETB receptors, which have been shown to be expressed in neurons of the trigeminal ganglion of humans and rats. The present study aimed to evaluate the ability of endothelin-1 (ET-1) to induce facial heat hyperalgesia in female rats, the contribution of ETA and ETB receptors to this response, as well as the mechanisms underlying heat hyperalgesia induced by ET-1. DESIGN: ET-1 (100pmol/50µL) was injected into the upper lip and heat hyperalgesia was evaluated for up to 6h. Facial heat hyperalgesia induced by ET-1 was assessed in rats pre-treated locally with BQ-123 or BQ-788 (selective ETA and ETB receptor antagonists, respectively, 30nmol/50µL); BCTC (TRPV1 receptor antagonist; 300µg/50µL); anti-NGF (3µg/50µL); K252a (TrkA inhibitor, 1µg/50µL); or in rats that received intraganglionar resiniferatoxin injection (RTX, 200ng/10µL) to promote C-fibers ablation. RESULTS: ET-1 induced facial heat hyperalgesia that persisted up to 6h and was prevented by BQ-123, BQ-788 or by intraganglionar RTX injection. Likewise, local pre-treatment with BCTC abolished ET-1 induced facial heat hyperalgesia up to 3h. Local pre-treatment with anti-NGF or K252a was effective to prevent ET-1 induced heat hyperalgesia. CONCLUSIONS: In conclusion, ET-1 is able to induce heat hyperagelsia in trigeminal primary afferents of female rats, which is mediated by ETA and ETB receptors. Activation of TRPV1 receptors and NGF-signaling pathways may contribute to heat hyperalgesia induced by ET-1.

Mechanisms of craniofacial pain.

Aim To provide an overview of mechanisms underlying craniofacial pain; to highlight peripheral and central adaptations that may promote chronification of pain in craniofacial pain states such as migraine and temporomandibular disorders (TMD). Background Pain is a common symptom associated with disorders involving craniofacial tissues including the teeth and their supporting structures, the temporomandibular joint and the muscles of the head. Most acute painful craniofacial conditions are easily recognized and well managed, but others, especially those that are chronic (e.g., migraine, TMD and trigeminal neuropathies), present clinical challenges. Preclinical studies have provided substantial information about the anatomical and physiological mechanisms related to the initiation and modulation of nociceptive signals in the trigeminal system. While knowledge of the mechanisms underlying chronic craniofacial pain remains limited, both clinical and preclinical investigations suggest that changes in afferent inputs to the brain as well as in brain structure and modulatory pathways occur in chronic pain. Collectively, these changes result in amplification of nociception that promotes and sustains craniofacial chronic pain states. Conclusions The increased understanding gained of the physiological and pathological processing of nociception in the trigeminal system has provided new perspectives for the mechanistic understanding of acute craniofacial pain conditions and the peripheral and central adaptations that are related to pain chronification. Such knowledge may contribute to improvements in currently available treatments as well as to the development of novel analgesic therapies.

Descripción de las propiedades funcionales del sistema nociceptivo trigeminal en relación con el dolor pulpar / Description of the functional properties of the nociceptive trigeminal system in relation to pulpal pain

El sistema trigeminal nociceptivo es un componente del sistema sensorial somestésico que tiene la capacidad de discriminar cuatro variables básicas de los estímulos que provocan daño tisular, ellas son: cualidad, curso temporal, localización e intensidad. Las fibras A delta y C, vinculadas a la nocicepción están presentes en la pulpa dental. Se utilizan varias clasificaciones del dolor, atendiendo a diversos criterios: calidad de la sensación, velocidad de transmisión por las fibras, en relación con el lugar del cuerpo donde se exprese, y a la ubicación del nociceptor. La evolución de las condiciones pulpares se clasifican como: pulpitis reversible, pulpitis transicional, pulpitis irreversible y pulpa necrótica.Según su cualidad, el dolor pulpar puede ser punzante o continuo; atendiendo a su aparición, provocado o espontáneo; por su curso, intermitente o continuo; por su localización puede ser limitado a una región, irradiado y referido; y en relación con su intensidad se considera leve, moderado o severo. La capacidad del sistema sensorial nociceptivo en cuanto a discriminar la modalidad, curso temporal, localización e intensidad del estímulo, permite conocer las diferentes etapas de un proceso inflamatorio pulpar(AU)

The nociceptive trigeminal system is a component of the somatosensory system capable of distinguishing four basic variables of stimuli causing tissue damage: quality, time course, location and intensity. A-delta and C fibers, which are related to nociception, are present in dental pulp. Several classifications of pain are used, based on various criteria: quality of the sensation, transmission velocity along fibers, body part where it is expressed, and location of the nociceptor. According to their evolution, pulpal conditions are classified into reversible pulpitis, transitional pulpitis, irreversible pulpitis and necrotic pulp. Pulpal pain has been classified according to the following variables: quality: sharp or continuous; cause: provoked or spontaneous; course: intermittent or continuous; location: limited to a region, radiating or referred; and intensity: mild, moderate or severe. The capacity of the nociceptive sensory system to distinguish the mode, time course, location and intensity of the stimulus makes it possible to recognize the different stages of a pulpal inflammatory process(AU)

Fisiopatología de la migraña: Teoría vascular, ¿Cierta o no? / Pathophysiology of migraine: vascular theory, true or not?

La migraña es una enfermedad de alta prevalencia, incapacitante y en algunas ocasiones de difícil manejo. Desde hace décadas se han planteado múltiples teorías para explicar su curso, su componente genético y la asociación a distintos factores de riesgo. Actualmente se desconoce una fisiopatología única y exacta que implique los eventos, y se ha encontrado fuerte evidencia que muestra que la teoría más antigua y con mayor sustento, a saber la teoría vascular, es en realidad incorrecta, pues no explica la totalidad de los eventos. Sin embargo, se han probado distintos mecanismos que, en conjunto, permiten comprender las alteraciones presentes. Entre estas se cuentan cambios estructurales, implicación de neuropéptidos, sensibilización, e inflamación neurogénica.

Migraine is a highly prevalent disease; it is disabling, and sometimes difficult to manage. For decades, many theories have been proposed to explain its course, its association with a genetic component and with different risk factors. There is currently no single and exact pathophysiology that accounts for all events, and strong evidence has been showing that the oldest theory believed to be mostly true, i.e. the vascular theory, is actually incorrect, because it does not explain the totality of the events. However, various mechanisms have been proven to exist, which together, provide insight into alterations, such as structural changes involving neuropeptides, sensitization, and neurogenic inflammation.

The relationship between the stomatognathic system and body posture: [review]

In recent years, many researchers have investigated the various factors that can influence body posture: mood states, anxiety, head and neck positions, oral functions (respiration, swallowing), oculomotor and visual systems, and the inner ear. Recent studies indicate a role for trigeminal afferents on body posture, but this has not yet been demonstrated conclusively. The present study aims to review the papers that have shown a relationship between the stomatognathic system and body posture. These studies suggest that tension in the stomatognathic system can contribute to impaired neural control of posture. Numerous anatomical connections between the stomatognathic system's proprioceptive inputs and nervous structures are implicated in posture (cerebellum, vestibular and oculomotor nuclei, superior colliculus). If the proprioceptive information of the stomatognathic system is inaccurate, then head control and body position may be affected. In addition, the present review discusses the role the myofascial system plays in posture. If confirmed by further research, these considerations can improve our understanding and treatment of muscular-skeletal disorders that are associated with temporomandibular joint disorders, occlusal changes, and tooth loss.