Foram avaliados os resultados, as alterações hemodinâmicas sistêmicas e as alterações da sensibilidade geral superficial de 31 doentes com neuralgia idiopática do trigêmeo tratados com a técnica de compressão percutânea do gânglio trigeminal com balão sob anestesia geral associadamente ou não ao bloqueio anestésico do gânglio trigeminal com lidocaína. As características biométricas, demográficas e clínicas foram similares nos doentes tratados (CBA) ou não (SBA) com bloqueio anestésico. As médias das pressões arteriais sistólicas (PASs), médias (PAMs) e diastólicas (PADs) e das frequências cardíacas foram analisadas nos momentos preoperatório imediato, anestesia geral e sem manipulação operatória, punção ganglionar, insuflação do balão e despertar e as sensibilidades faciais nos momentos pré-operatório e de 30 e 210 dias posoperatórios. As médias das PASs, das PAMs e das PADs foram inferiores nos doentes do grupo CBA em relação às dos doentes do grupo SBA nos momentos punção ganglionar e insuflação do balão do balão e as médias das PAMs e PADs foram inferiores nos doentes do grupo CBA em relação às do grupo SBA no momento despertar. Ocorreu elevação da PAS, PAM e PAD em todos os doentes hipertensos ou não do grupo SBA. Ocorreu elevação da PAM em 16,7% dos normotensos e em 33,3% dos hipertensos e em 33,3% dos normotensos e em 11,1% dos hipertensos do grupo CBA, respectivamente, nos momentos, punção ganglionar e insuflação do balão. Ocorreu hipertensão arterial em 50 a 75% dos doentes do grupo SBA e em zero a 7% dos doentes do grupo CBA nos momentos punção ganglionar e insuflação do balão. Todos os doentes normotensos do grupo CBA apresentaram redução da PAS e da PAM e, 83,3%, também da PAD no momento punção do gânglio trigeminal. Ocorreu redução da PAS e da PAM em 83,3% dos doentes normotensos do grupo CBA e, em 66,7%, da PAD no momento insuflação do balão. Em 55,6% dos hipertensos do grupo CBA ocorreu redução das PAS e da PAM e, em 66,7%, da PAD no momento punção ganglionar. Observou-se redução da PAS em 66,7% dos doentes hipertensos do grupo CBA e da PAM e da PAS em 88,9%. Ocorreu redução da PAS e da PAM em 83,3% dos doentes normotensos do grupo CBA e da PAD em 66,7%. Ocorreu hipotensão arterial em 27% a 33% dos doentes do grupo CBA e em nenhum dos do grupo SBA. As frequências cardíacas dos doentes do grupo SBA elevaram-se e mantiveram-se mais elevadas que as dos do grupo CBA nos momentos anestesia geral sem manipulação operatória, punção ganglionar, insuflação do balão e despertar. Todos os doentes do grupo SBA e 90% dos do grupo CBA não apresentavam dor sete meses após a operação. Ocorreu recidiva da dor em 26,7% dos doentes; ocorreu em uma a 128 (71,13 ± 55,23) semanas após a cirurgia ou seja em 121,07 ± 23,05 semanas em média; não houve diferença estatisticamente significativa entre os doentes dos grupos SBA e CBA quanto à recidiva ou não da dor. Na avaliação de 30 e 210 dias, os valores da algiometria na região do segundo ramo (V2) do nervo trigêmeo nos doentes do grupo CBA foram mais elevados em ambos os lados da face que nos doentes do grupo SBA e não se modificaram ao longo do período das avaliações. A algiometria no território do primeiro ramo (V1) do nervo trigêmeo não se modificou ao longo dos sete meses de avaliação e não diferiu entre os doentes de ambos os grupos. A maioria dos doentes apresentava hipoalgesia no território de inervação de V2 e V3 um mês após a operação; a sensibilidade dolorosa não se modificou em cerca de metade dos doentes de ambos os grupos e manteve-se inalterada em 25% a 33% dos doentes A intensidade da dormência e do incômodo associado a ela foram maiores um e sete meses após a operação nos doentes de ambos os grupos; 14,3% dos doentes do grupo SBA não apresentava sensação de dormência facial um mês após a operação. Todos os doentes do grupo SBA e 90% dos do grupo CBA apresentavam dormência facial sete meses após a operação. Sete meses após a operação, a sensibilidade dolorosa no território de V1 não se modificou em metade dos doentes de ambos os grupos, foi normal na região de V2 em 50% e 41,7% dos doentes dos grupos CBA e SBA, respectivamente, e na região de V3 em 40% dos doentes do grupo CBA e em nenhum do grupo SBA, respectivamente. As alterações da sensibilidade dolorosa na região de V3 foram menores nos doentes do grupo CBA que nos do grupo SBA. Houve aumento de doentes do grupo SBA que apresentaram hipoalgesia facial nas regiões de V1, V2 e V3 um mês após a operação. Nos doentes do grupo CBA ocorreu hipoalgesia apenas na região de V3 um mês após a cirurgia e redução não significativa destas alterações sete meses após. O exame da sensibilidade ao frio foi normal no território de V1 em cerca de metade dos doentes um mês após a operação; houve aumento da proporção de doentes com hipoestesia ou anestesia ao frio nos territórios de V2 ou V3. Na maioria dos doentes, a sensibilidade ao frio nos territórios de V1 e V2 normalizou-se, mas manteve-se comprometida no território de V3 sete meses após a operação. Nos doentes do grupo SBA não se identificaram alterações significativas da sensibilidade facial ao frio nas regiões de V1 e V2, mas ocorreu aumento significativo de casos com hipoestesia ao frio na região de V3 um e sete meses após a operação. Houve hipoestesia ao frio somente na região de inervação de V2, um e sete meses após a operação nos doentes do grupo CBA. Um mês após a operação, a proporção de doentes com sensibilidade normal ao calor reduziu-se para 42,9% e 21,4% em V1 e V3, respectivamente, nos doentes de ambos os grupos. Sete meses após a operação, a proporção de doentes com sensibilidade normal ao calor reduziu-se para 33,3%, 41,7% e 8,3%, respectivamente, em V1, V2 e V3 nos doentes do grupo SBA e elevou-se para 50,0%, 40,0% e 40,0% respectivamente, nos doentes do grupo CBA, mas as diferenças não foram significativas. Ocorreu aumento significativo da hipoestesia ao calor apenas na região de inervação de V3 dos doentes do grupo SBA e do número de doentes do grupo CBA com hipoestesia ao calor nas regiões de inervação de V2 e V3 um e sete meses após a operação. Não houve diferença estatisticamente significativa entre os doentes de ambos os grupos quanto à sensibilidade tátil nos momentos preoperatório, um mês e sete meses após a operação. Os doentes do grupo SBA apresentaram significativa hipoestesia tátil no território de V1 ao longo dos períodos de avaliação. Não houve diferença estatística entre os grupos em relação ao exame da sensibilidade tátil no território de V2 e de V3 ao longo dos momentos da avaliação. Evidenciou-se hipoestesia tátil no território de V3 ao longo das avaliações pós-operatórias nos doentes do grupo SBA e não houve alterações significativas da sensibilidade tátil ao longo das avaliações nos doentes do grupo CBA. Não ocorreu diferença entre os doentes de ambos os grupos quanto aos achados da pesquisa do reflexo corneopalpebral ao longo das avaliações / The clinical results, the systemic hemodynamic reactions and the modification of the general superficial sensorial examination of 31 patients with idiopathic trigeminal neuralgia treated with percutaneous compression technique of the trigeminal ganglion with balloon under general anesthesia associated or not with block the trigeminal ganglion with local anesthetic were evaluated. The biometric, demographic and clinical characteristics were similar in patients treated (CBA) or not (SBA) with trigeminal ganglion block. The averages of the systolic (PASs), mean (PAMs) and diastolic (PADs) arterial pressures and heart rates were evaluated in the preoperative period, during the general anesthesia and before the surgical manipulation, during the trigeminal ganglion puncture, during the balloon expansion and the awakening period and the facial sensibility at the immediate preoperative and at the 30th and 210th postoperative days. In the CBA group, the averages of PASs, PAMs and PADs were lower than in CBA patients during the trigeminal ganglion puncture and expansion of the balloon and the averages of the PAMs and PADs were lower in CBA patients than in SBA patients during the awakening period. There was increasing of the mean PAS, PAM and PAD on all hypertensive or not SBA patients. There was increasing of the PAM in 16.7% of the normotensive and in 33.3% of the hypertensive and in 33.3% of normotensive CBA patients and in 11.1% of hypertensive CBA patients, respectively, at the trigeminal ganglion puncture and balloon inflation times. Arterial hypertension was diagnosed in 50 to 75% of SBA patients and in none to 7% of CBA patients during the trigeminal ganglion puncture and balloon expansion. All normotensive CBA patients presented PAS and PAM reduction and 83.3%, also presented PAD reduction at the time of the trigeminal ganglion puncture. The PAS and PAM reduced in 83.3% of the normotensive CBA patients, and the PAD in 66.7% during the balloon inflation. In 55.6% of the hypertensive CBA patients, there was reduction of PAS and also of the PAM and in 66.7% of the PAD at the time of trigeminal ganglion puncture. There was reduction of PAS in 66.7% of hypertensive CBA patients and of the PAM and PAS in 88.9% of them. There was reduction of PAS and PAM in 83.3% of the normotensive CBA patients and of PAD in 66.7%. Arterial hypotension was observed in 27% to 33% of the CBA patients but not in the SBA patients. The cardiac rates of the SBA patients increased and remained higher than those of the CBA patients during the general anesthesia period previous to the surgical manipulation, trigeminal ganglion puncture, balloon expansion and awakening. All SBA and 90% of the CBA patients had no pain seven months after the operation. There was pain recurrence in 26.7% of the patients in one to 128 (71.13 ± 55.23) weeks after the surgical procedure, that is 121.07 ± 23.05 weeks of the postoperative period in average; there was no difference between SBA and CBA patients in relation to pain recurrence rate. The algiometry values in the region of the second branch (V2) of the trigeminal nerve in the CBA patients were higher on both sides of the face that in SBA patients in the 30th and 210th postoperative days. There was no difference between patients of both groups regarding the averages of the values of the postoperative algiometry. The algiometry did not change in the first branch (V1) of the trigeminal nerve over the seven months of the follow-up period and did not differ statistically between the patients from both groups. The majority of patients presented hipoalgesia in the territory of V2 and V3 one month after the operation. The hypoalgesia did not change in about half of the patients of both groups and remained unchanged in 25% to 33% of the patients. The intensity of the numbness and of the associated bad feeling were higher one and seven months after surgery in the patients of both groups. All SBA and 90% of CBA patients presented facial numbness seven months after the operation. Seven months after the operation, the numbness in the territory of V1 did not change in half the patients from both groups, was normal in the region of V2 in 50% and 41.7% of patients of the CBA and SBA groups, respectively, and in the region of V3 in 40% of patients of the CBA and in none of the SBA group, respectively. The pain sensory changes in V3 were smaller in the CBA than in SBA patients. There was increasing in the number of SBA patients who presented V1, V2 and V3 hipoalgesia of one month after the operation. Hypoalgesia was observed just in the V3 territory of the CBA patients one month after surgery and non-significant reduction of this finding seven months after the procedure. The sensitivity to cold was normal in the territory of V1 in about half of patients a month after the operation. There was increasing in the proportion of patients presenting hypoesthesia or anesthesia to cold in the territories of V2 or V3. In most patients, coldness perception in the V1 and V2 territories normalized but remained altered in the territory of V3 seven months after the operation in many of them. There were not significant changes in the facial sensitivity to cold in V1 and V2 territories in the SBA patients, but there was a significant increase of cases with cold hypoesthesia in the region of V3 one and seven months after the operation. There was cold hypoesthesia in the V2 region seven months after surgery in of CBA patients. One month after the operation, the proportion of patients from both groups with normal perception of heat in the face reduced to 42.9% and 21.4% in V1 and V3, respectively. Seven months after the operation, the proportion of patients with normal sensitivity to heat fell to 33.3%, 41.7% and 8.3%, respectively, in V1, V2 and V3 of patients from the SBA group and increased to 50.0%; 40.0% and 40.0%, respectively, in CBA patients, but the differences were not significant between both groups. There was a significant increase of heat hypoesthesia in V3 region, one and seven months after surgery in SBA patients. There was significant increase in the number of CBA patients presenting V2 and V3 heat hypoesthesia, one and seven months after the operation. There was no significant difference in the tactile sensitivity between the patients of both groups in the preoperative period and one month and seven months postoperatively. SBA patients presented significant tactile hypoesthesia in the V1 territory over the evaluation period. There was no difference between both groups of patients related to tactile sensitivity in the V2 territory during the follow up period. There was no difference between the groups in relation to V3 tactile sensitivity in the evaluation period. There was V3 tactile hypoesthesia along the post-operative evaluations in the SBA patients. There were no significant changes in the tactile sensitivity along the evaluations in the CBA patients. No difference was observed in the evaluation of the corneal reflex in the patients of both groups during the follow-up period

A expressão do receptor de potencial receptor transiente, vanilóide 1 (TRPV1) começa desde estágios pré-sinaptogênicos da retina. O bloqueio farmacológico desse receptor nesse período diminui a apoptose fisiológica, havendo possível envolvimento da sinalização de MAP quinases. Na retina do animal adulto, observamos que a expressão de TRPV1 é amplamente difundida, albergando neurônios, células endoteliais e células da microglia. A ativação dos receptores TRPV1 é potencialmente citotóxica, e os mecanismos que podem estar envolvidos incluem a liberação de glutamato, a excitotoxicidade e o estresse nitrosativo. Evidenciamos que a lesão prévia de células ganglionares sensibiliza o tecido retiniano à citotoxicidade mediada pela estimulação de TRPV1. Porém, o bloqueio de TRPV1, tanto in vivo quanto in vitro, não inibiu a morte de células ganglionares axotomizadas. Esses dados sugerem que o receptor TRPV1 participa da modulação de diversos processos fisiopatológicos na retina. / TRPV1 expression in the developing retina begins before retinal sinaptogenesis. TRPV1 blockade reduced the normal apoptosis in this period, and MAPK signaling seems to be involved in this process. In the adult retina, TRPV1 are expressed in neuronal, endothelial and microglial cells. The activation of those receptors is potentially cytotoxic, and glutamate release and further excitotoxicity and nitrosative stress might be also involved. Axotomized retinal ganglion cells were sensitized to TRPV1 citotoxicity, but TRPV1 antagonism, both in vitro and in vivo, did not reduce the loss of ganglion cell after axotomy. Our results suggest that TRPV1 receptors are involved in synaptic function and homeostatic control in the retina. Moreover, TRPV1 seems to be indirectly involved in cellular degeneration that follows the section of retinal ganglion cell axons.

Les douleurs oculaires aiguës et chroniques sont parmi les plus invalidantes et les plus difficiles à traiter. Elles touchent plus particulièrement la cornée, tissu le plus innervé et le plus sensible du corps humain. Cette riche innervation provient des neurones sensoriels primaires localisés dans le ganglion trijumeau (GT) qui transmettent directement l'information douloureuse au niveau du complexe sensitif du trijumeau (CST). Cependant, les mécanismes physiopathologiques de la douleur oculaire de nature neurogène et/ou inflammatoire demeurent de nos jours encore mal connus. Un approfondissement des connaissances fondamentales sur l'anatomie du système nociceptif cornéen mais aussi sur les mécanismes cellulaires et moléculaires impliqués dans l'initiation et la chronicisation de la douleur oculaire, sont donc indispensables à l'amélioration des thérapies actuelles. Dès lors, les travaux de cette thèse se sont donc orientés sur deux axes principaux ; 1) approfondir les connaissances neuroanatomiques du système nociceptif cornéen en établissant la première cartographie tridimensionnelle des neurones cornéens au sein du GT ; 2) étudier les conséquences neuro-inflammatoires des voies trigéminées cornéennes (cornée, GT et CST) dans un modèle murin de douleur oculaire induit par des instillations chroniques de chlorure de benzalkonium (conservateur neurotoxique). Dans l'ensemble, nos travaux expérimentaux montrent qu'une lésion cornéenne chez la souris induit une neuro-inflammation qui se propage de la périphérie jusqu'au système nerveux central, et offrent de nouvelles perspectives thérapeutiques pour les patients atteints de douleurs oculaires aiguës ou chroniques. / Acute and chronic eye pain are among the most debilitating and difficult to treat. They particularly affect the cornea, the most innervated and most sensitive tissue of the human body. Corneal innervation comes from primary sensory neurons localized in the trigeminal ganglion (TG) that directly transmit pain information to the trigeminal sensory complex (TSC). However, pathophysiological mechanisms of ocular pain with neurogenic and /or inflammatory type remain poorly understood. Deeper fundamental knowledge about the anatomy of the corneal nociceptive system and the cellular and molecular mechanisms involved in the initiation and chronicity of eye pain, are essential to improving current therapies. Therefore, the work of this thesis are focused on two main topic: 1) expand our current knowledge about the neuroanatomy of the corneal nociceptive system by establishing the first three-dimensional mapping of corneal neurons within the TG; 2) study the neuro-inflammatory consequences in the corneal trigeminal pathways (cornea, TG and TSC) in a murine model of ocular pain induced by chronic instillations of benzalkonium chloride (neurotoxic preservative). Overall, our experimental work reveals that a corneal lesion in mice induces neuroinflammation that spreads from the periphery to the central nervous system, and offer new therapeutic opportunities for patients with acute or chronic eye pain.

V minul©m stolet­ byl vynaloen znaÄn vzkum na pochopen­, jak jsou vizuln­ informace kdovny neurln­mi populacemi a jejich obvody. Celkov obraz, kter vyplynul z tohoto sil­, naznaÄuje, e vizuln­ informace jsou nejprve zpracovny sloitmi obvody v s­tnici a nslednÄ peneseny do vy­ch mozkovch struktur. Ukazuje se, e s­tnice i mozek si vyvinuly pozoruhodnÄ sofistikovan© vpoÄty pro extrakci tÄchto informac­. FunkÄn­ studie tÄchto neuronln­ch transformac­ byly provdÄny pomoc­ elektrofyziologickch nebo zobrazovac­ch technik. Tyto techniky omezovaly analzu prostorovch specializac­ s­tnice, a to buÄ poÄtem dostupnch elektrod (v elektrofyziologii) nebo velikost­ zorn©ho pole (FOV) (v zobrazovac­ch experimentech). Pro ukzku â zznamy aktivit gangliovch bunÄk s­tnice (RGC) byly omezeny na relativnÄ malou oblast (~ 200 x 200 um2) za pouit­ nejmodernÄj­ch zobrazovac­ch technik. Ve sv© diplomov© prci jsem prozkoumal novÄ vyvinutou metodu vyu­vaj­c­ FOV, kter je 40krt vÄt­ ve srovnn­ s FOV konvenÄn­ch optickch metod, co mi umoilo pekonat toto technick© omezen­. Prce vyu­v tuto novou zobrazovac­ metodu k prozkoumn­ populaÄn­ch charakteristik smÄrovÄ selektivn­ch gangliovch bunÄk (DSGC) v s­tnic­ch my­. Replikac­ ji znmch populaÄn­ch vzorc jsme verifikovali, e nae nov zobrazovc­ metoda funguje. Prce dle zkoum Äinky pomocnch ltek pro zven­ m­ry infekce RGCs. Tyto pomocn© ltky tak mohou potencilnÄ usnadnit nezaujat© zaznamenvn­ aktivit RGCs. Prce nav­c pedstavuje nov stimul pro inspekci receptivn­ch pol­ (RF) RGCs. Tento nov stimul pekonv konvenÄn­ stimuly pou­van© v souÄasnch studi­ch jak v rozlien­ vyprodukovan©ho RF, tak v nezbytn©m Äase prezentace stimulu a otev­r tak dvee pro nsleduj­c­ studie, kter© mohou poprv© popsat distribuÄn­ vzorce receptivn­ch poli nap­Ä s­tnic­ a zlepit tak klasifikaci bunÄÄnch t­d.

De nombreuses études s’intéressent aux comportements décisionnels et d’apprentissage ainsiqu’aux structures qui les sous-tendent. Il a été montré que le Cortex Préfrontal (CPF) ainsiqu’un réseau de structures sous-corticales, les Ganglions de la Base (GB), étaient impliquésdans ces processus. Néanmoins, le rôle respectif de chacun n’est pas définit. Deux hypothèsessont émises. La première stipule que les deux structures fonctionnent indépendamment. LesGB seraient impliqués dans les comportements habituatifs tandis que le CPF se chargerait descomportements planifiés. La seconde hypothèse considère que les deux structures collaborent: les GB contrôleraient un processus d'apprentissage à cinétique lente dans le CPF et sedésengageraient progressivement au fur et à mesure de l’apprentissage. Ceci reviendrait d'unecertaine façon à inverser les rôles : les GB seraient nécessaires aux processus de décision tantque le CPF n'aurait pas fini son apprentissage. Celui-ci fonctionnerait ensuite sur un modeautomatique. Le principal obstacle à l’étude respectif du rôle des GB et du CPF dans cesprocessus intervient dans les paradigmes expérimentaux qui ne dissocient pas la prise dedécision per se des processus d’apprentissage. Notre premier objectif a donc été d’élaborerune tâche expérimentale qui permette de différencier les phases d’apprentissage des phases deprise de décision. Nous avons ensuite supprimé l'influence des GB sur le cortex, en inhibantleur structure de sortie, le Globus Pallidus interne (GPi) par des injections intracérébrales demuscimol chez le primate non-humain effectuant une tâche comportementale : le "two armedbandit task". Nous montrons que les animaux sont toujours capables de prendre des décisionsaprès inhibition du GPi mais qu’ils sont incapables d’apprendre la valeur de nouvelles cibles.Ces résultats confirment que, chez le primate en tous les cas, les GB et le CPF sont bienimpliqués dans un processus collaboratif : l'intégrité de l'ensemble du circuit est nécessairepour l'apprentissage alors que le cortex seul peut suffire une fois que le choix se situe dans uncontexte habituel. / Many studies are interested in decision making and learning processes and in brainareas which are engaged in. Among them, the implication Prefrontal Cortex (PFC) and a subcortical structures’ network, the Basal Ganglia (BG) has been shown. Nevertheless, theprecise role of each structure has not yet been defined. There are two main hypotheses. Thefirst one holds that GB and PFC function independently. BG would support habitualbehaviors and PFC planned behaviors. The second hypothesis proposes that both structuresare collaborating: the basal ganglia drive a low kinetic learning process in the prefrontalcortex and become less and less engaged as the task is learned. It means reversing the roles:BG would be necessary for decision making processes as soon as PFC finishes its learning.This latter would then function as an automatic mode. The main problem which avoids us todisentangle the role of each structure is the experimental paradigms used which mix uplearning and decision making. Our first aim was to design an experimental task in which therewas learning phase and decision making phase per se. Then, we blocked basal gangliainfluence on PFC by inhibiting their exit structure, the Globus Pallidus internal, withintracerebral muscimol injections in non-human primates performing a “two-armed bandittask”. Our results show that monkeys are able to do decision making after GPi inhibition butthey are unable to learn new values. These results confirm that, in non-human primates, BGand PFC are well involved as co-workers in one process: integrity of all the circuit isnecessary for learning whereas only cortex is sufficient once the choice is in habitual context.

The localization of substance P (SP) binding sites in guinea-pig heart was studied by in vitro autoradiography, and pharmacological effects of SP were examined with isolated heart preparations. Specific binding of [125I]SP was found in association with cardiac parasympathetic ganglia and some coronary arteries. No specific SP binding sites were associated with coronary veins, atria, ventricles, ascending aorta or pulmonary trunk. Local bolus injections of SP (2.5 and 25 nmol) caused a bradycardia which, in some preparations, was followed by a slight tachycardia. SP produced a prominent coronary vasodilator effect after basal perfusion pressure had been elevated by 1 μM vasopressin. The vasodilator response was probably mediated by the SP binding sites associated with the coronary arteries. Bradycardia might be elicited by binding of SP to the receptors present in the parasympathetic ganglia and subsequent release of acetylcholine. It is suggested that these effects of SP on the isolated heart could be of physiological significance.

Intravenous injection of 3-33 nmol/kg of substance P (SP) caused pressor and tachycardic responses in anesthetized rats. The responses were not blocked by a ganglion nicotinic receptor antagonist or by pithing. Pretreatment with reserpine blocked both responses. β-Adrenoceptor blockade attenuated only the tachycardic response, and α-adrenoceptor blockade attenuated only the pressor response. These findings indicated that the effects of SP to increase blood pressure and heart rate are due to sympathetic ganglion stimulation. Studies with adrenalectomized rats showed that stimulation of the adrenals by SP contributes to both responses but makes a greater contribution to the tachycardic response. These observations raise the possibility that the tachykinin innervation of sympathetic ganglia and the adrenal medulla may be involved in the local regulation of blood pressure and heart rate.

Distribution of cocaine- and amphetamine-regulated transcript-like immunoreactivity (CART-LI) was studied in the rat spinal cord, sympathetic ganglia and adrenal glands by immunohistochemical methods, utilizing a polyclonal antiserum raised against the CART peptide fragment 55-102. CART-LI was detected in nerve fibers and in basket-like terminals surrounding many postganglionic neurons of the superior cervical ganglion (SCG), stellate, paravertebral and prevertebral ganglia. Postganglionic neurons exhibited low or non-detectable levels of CART-LI. Surgical sectioning of the cervical sympathetic trunk for 6-7 days resulted in a nearly complete loss of CART-LI fibers and terminals in the SCG. In the adrenal gland, CART-LI nerve fibers formed a plexus underneath the capsule, some of which bifurcated and made a sharp turn toward the adrenal medulla, where clusters of chromaffin cells were intensely labeled. The detection of CART-LI in sympathetic ganglia and adrenal glands extends the previous observation of the presence of CART-LI in sympathetic preganglionic neurons and further supports the notion that CART peptide(s) may function as a signaling molecule in the sympatho-adrenal axis.

Intravenous injection of substance P (SP) increases blood pressure in normotensive rats by stimulating sympathetic ganglia. This study compared the effects of SP to increase renal nerve firing and blood pressure in normotensive and hypertensive rats treated with chlorisondamine. The increase in renal nerve firing was greatest in spontaneously hypertensive rats (SHR), intermediate in Wistar rats, and least in Wistar-Kyoto (WKY) rats. Blood pressure was increased more in SHR than in Wistar rats. Blood pressure was not increased in WKY rats. Responses to the ganglionic stimulant 1, 1-dimethyl-4-phenylpiperazinium were the same in the three strains. These results suggest that there is a selective increase in the action of SP on sympathetic ganglia of SHR and that ganglion responsiveness to SP is correlated with its effect on blood pressure.

Populations of intrathoracic extracardiac neurons transduce myocardial ischemia, thereby contributing to sympathetic control of regional cardiac indices during such pathology. Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) modulates such local reflex control. In 10 anesthetized canines, middle cervical ganglion neurons were identified that transduce the ventricular milieu. Their capacity to transduce a global (rapid ventricular pacing) vs. regional (transient regional ischemia) ventricular stress was tested before and during SCS (50 Hz, 0.2 ms duration at 90% MT) applied to the dorsal aspect of the T1 to T4 spinal cord. Rapid ventricular pacing and transient myocardial ischemia both activated cardiac-related middle cervical ganglion neurons. SCS obtunded their capacity to reflexly respond to the regional ventricular ischemia, but not rapid ventricular pacing. In conclusion, spinal cord inputs to the intrathoracic extracardiac nervous system obtund the latter's capacity to transduce regional ventricular ischemia, but not global cardiac stress. Given the substantial body of literature indicating the adverse consequences of excessive adrenergic neuronal excitation on cardiac function, these data delineate the intrathoracic extracardiac nervous system as a potential target for neuromodulation therapy in minimizing such effects.