Blockade of opioid receptors in the medullary reticularis nucleus dorsalis, but not the rostral ventromedial medulla, prevents analgesia produced by diffuse noxious inhibitory control in rats with muscle inflammation.

UNLABELLED: Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45 °C and 47 °C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. PERSPECTIVE: The current study shows that DNIC activates opioid receptors in the MdD, but not the RVM, to produce analgesia. These data are important for understanding clinical studies on DNIC as well as for potential treatment of chronic pain patients.

Involvement of 5-HT(2) serotonergic receptors of the nucleus raphe magnus and nucleus reticularis gigantocellularis/paragigantocellularis complex neural networks in the antinociceptive phenomenon that follows the post-ictal immobility syndrome.

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.

C-fos expression in rat brain nuclei following incisor tooth movement.

In the rat experimental model, molar tooth movement induced by Waldo's method is known to cause a temporally and spatially defined pattern of brain neuronal activation. Since orthodontic correction usually involves the entire dental arch, we used a spring-activated appliance to extend the investigation to incisors, and we included brain regions related to antinociception. Adjustment of the non-activated appliance on incisors resulted in c-fos expression in the dorsal raphe, peri-aqueductal gray matter, and the locus coeruleus, in addition to trigeminal sensory subnuclei and the parabrachial nucleus, where neuronal activation has already been detected in previous studies on molar tooth movement. Appliance activation with a 70-g force resulted in a further increase in Fos-immunoreactive neurons in the trigeminal sensory subnucleus caudalis and in the dorsal raphe. This result suggests that there is a recruitment of neurons related to nociception and to antinociception when tooth movement is increased.

Probable mielinolisis central pontina asociada a intoxicación por órganofosforados: hipótesis sobre una nueva etiología / Central pontine myelinolysis associated to organophosphorous insecticide

La mielinolisis central pontina (MCP) es un cuadro de alteración neurológica aguda y progresiva patológicamente caracterizada por desmielinización protuberancial y/o extraprotuberancial, etiológicamente asociada a una inadecuada corrección de la hiponatremia, por lo que también se denomina Síndrome de desmielinización osmótica. Presentamos una paciente intoxicada accidentalmente con un compuesto órganofosforado (OF), que presentó inicialmente un cuadro clínico y de laboratorio secundario a la inhibición y recuperación aguda de la actividad plasmática de la acetilcolinesterasa (intoxicación de Tipo 1). La evolución neurológica posterior resultó compatible con lesión de tallo cerebral. No se registraron alteraciones de la temperatura, la natremia, el pH ni los gases en sangre. En estadio agudo las imágenes por Resonancia Magnática (RM), mostraron lesión centroprotuberancial única y ovoide, hipointensa en T1 e hiperintensa en T2, sin edema periférico ni efecto de masa, sin signos hemorrágicos y sin cambios con el gadolinio, hallazgos estrechamente correlacionados con probable MCP. No se evidenciaron lesiones extrapontinas. Un examen neurológico de control a los 90 días no mostró anormalidades, mientras que en las imágenes por RM la lesión protuberancial mostraba signos involutivos; ambos resultados son coincidentes con los de trabajos previos sobre MCP en su evolución tardía. Se descartaron otras causas de lesión protuberancial en base a los antecedentes, la forma de presentación y la evolución aguda y crónica, tanto clínica como en RM. Se discuten los mecanismos de acción patogénica de los compuestos OF sobre la mielina, que apoyan la hipótesis etiológica propuesta. Concluimos que la relación causal, la evolución neurológica y los hallazgos en RM en una paciente normonatrémica, permiten proponer a la intoxicación por compuestos OF como una probable nueva etiología de MCP

Probable mielinolisis central pontina asociada a intoxicación por órganofosforados: hipótesis sobre una nueva etiología / Central pontine myelinolysis associated to organophosphorous insecticide

La mielinolisis central pontina (MCP) es un cuadro de alteración neurológica aguda y progresiva patológicamente caracterizada por desmielinización protuberancial y/o extraprotuberancial, etiológicamente asociada a una inadecuada corrección de la hiponatremia, por lo que también se denomina Síndrome de desmielinización osmótica. Presentamos una paciente intoxicada accidentalmente con un compuesto órganofosforado (OF), que presentó inicialmente un cuadro clínico y de laboratorio secundario a la inhibición y recuperación aguda de la actividad plasmática de la acetilcolinesterasa (intoxicación de Tipo 1). La evolución neurológica posterior resultó compatible con lesión de tallo cerebral. No se registraron alteraciones de la temperatura, la natremia, el pH ni los gases en sangre. En estadio agudo las imágenes por Resonancia Magnática (RM), mostraron lesión centroprotuberancial única y ovoide, hipointensa en T1 e hiperintensa en T2, sin edema periférico ni efecto de masa, sin signos hemorrágicos y sin cambios con el gadolinio, hallazgos estrechamente correlacionados con probable MCP. No se evidenciaron lesiones extrapontinas. Un examen neurológico de control a los 90 días no mostró anormalidades, mientras que en las imágenes por RM la lesión protuberancial mostraba signos involutivos; ambos resultados son coincidentes con los de trabajos previos sobre MCP en su evolución tardía. Se descartaron otras causas de lesión protuberancial en base a los antecedentes, la forma de presentación y la evolución aguda y crónica, tanto clínica como en RM. Se discuten los mecanismos de acción patogénica de los compuestos OF sobre la mielina, que apoyan la hipótesis etiológica propuesta. Concluimos que la relación causal, la evolución neurológica y los hallazgos en RM en una paciente normonatrémica, permiten proponer a la intoxicación por compuestos OF como una probable nueva etiología de MCP (AU)

Electroencephalographic and magnetic resonance correlations in children with intractable seizures of Lennox-Gastaut syndrome and epilepsia partialis continua.

A study was performed of EEG-magnetic resonance imaging (MRI) abnormalities in 7 Lennox-Gastaut syndrome (LGS) children and 3 epilepsia partialis continua (EPC) children with intractable generalized and partial motor seizures, respectively. In 4 children with LGS and 3 children with EPC, depth electrodes were implanted in the centromedian thalamic nuclei (CM) for seizure control. In all children with LGS, hyperdense, T2-weighted MRI signals were observed at the mesencephalic level of the brainstem, whereas none of the 3 children with EPC had this finding. Patients with idiopathic LGS without cerebral hemisphere MRI abnormalities showed generalized bilateral and symmetrical spike-wave EEG activity. Patients with symptomatic LGS with unilateral hemispheric MRI abnormalities demonstrated asymmetrical EEG activity with higher amplitude spike-and-wave over the normal hemisphere. Patients with EPC with unilateral hemispheric lesions had lateralized higher amplitude spike-wave over the damaged hemisphere. These data suggest that abnormal mesencephalic MRIs are a sign of bad prognosis in patients with LGS but not with EPC. Maximal amplitude paroxysmal EEG activities may indicate the abnormal hemisphere in patients with EPC or the normal hemisphere in those with LGS.