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Antonio A. F. DeSalles, Yoichi Katayama, Donald P. Becker and Ronald L. Hayes

✓ Cholinergic stimulation by microinjection of drugs into a region surrounding the lateral half of the brachium conjunctivum selectively produces a non-opiate form of pain suppression in the cat. Since this suppression does not appear to involve neural systems that mediate morphine analgesia, stimulation of this pontine parabrachial region (PBR) may potentially be useful for control of human pain resistant or tolerant to opiate treatment. Because of technical problems associated with the clinical use of microinjection techniques in the human brain, we investigated whether electrical stimulation of the PBR can produce pain suppression similar to pain suppression produced by cholinergic stimulation. The results indicate that electrical stimulation of an area generally corresponding to the PBR can also produce significant pain suppression. Although the PBR is a region previously implicated in a variety of behavioral and physiological functions, the stimulation parameters that produce maximal pain suppressive effects (namely, low frequency and relatively low intensity) were not associated with noticeable changes in such functions. The prolonged onset period and persistent analgesic effects outlasting the period of stimulation — features that have been reported in other studies of brain stimulation-produced pain suppression — were observed in the present study. The time course of pain suppression did not parallel other changes in behavioral and physiological functions. These data indicate that electrical stimulation of the PBR, under certain stimulation parameters, can activate previously demonstrated neural populations related to pain suppression without affecting neural elements contributing to other behavioral or physiological functions. The authors suggest that electrical stimulation of the PBR may be clinically applicable for treatment of human pain.

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which showed that application of carbachol to this area with and without naloxone also produces analgesia. It is therefore apparent from these two studies that the parabrachial nucleus may mediate a non-opiate mechanism to suppress pain. In reviewing the literature on efferent connections made by this relatively small crescent-shaped pontine complex of neurons surrounding the brachium conjunctivum, Saper and Loewy 3 found that, besides providing wide-ranging projections to the cortex, amygdala, hypothalamus, midline and ventromedial basal thalamic nuclei, raphe and

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Charles J. Hodge Jr., A. Vania Apkarian and Richard T. Stevens

the medial border of the brachium conjunctivum and blend with the ceils of the KF. The KF is found at the most ventral tip of the brachium conjunctivum. 6, 7 Fig. 1. Left: Cross section of the pons at posterior level 3.1 showing the anatomic locations of the nucleus locus ceruleus (LC), the nucleus subceruleus (SC), the Kölliker-Fuse nucleus (KF), the lateral parabrachial nucleus (PBL), the brachium conjunctivum (BC), and the fourth ventricle (4). The black bar is equivalent to 1 mm. Right: Line drawing of the same section showing the locations of

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Ronald F. Young, Volker Tronnier and Patricia C. Rinaldi

Baxter, 25 implanting the electrode in the parabrachial nucleus (nucleus marginalis brachii conjunctivi of Berman) and the nucleus tegmenti pedunculopontinus based on translation of the coordinates. Recognizing the problems inherent in this translation, we approached the problem as did Hodge, et al. , 13 by attempting to identify neurons of the mesencephalic nucleus of the trigeminal nerve with jaw opening by the patients. When this proved unsuccessful and there were no useful electrophysiological signs, the locus ceruleus was targeted and the coordinates corrected

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Lawrence D. Dickinson, Stephen M. Papadopoulos and Julian T. Hoff

hypothalamic nuclei. 3, 4, 18 These centers receive reciprocal innervation from each other and also innervation from rostral brain regions involved in cardiovascular and respiratory regulation. Secondary inputs include the lateral parabrachial nucleus, the Kölliker-Fuse nucleus, the area postrema, and areas of limbic and frontal cortex. Fig. 3. Schematic representation of the anatomical regions involved in blood pressure regulation. The arrows represent pathways demonstrated by neuroanatomical studies and confirmed physiologically to have effects on systemic

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Marcus F. Keep, Lois Mastrofrancesco, Arthur D. Craig and Lynn S. Ashby

stroke and region of radiosurgical CMN thalamotomy. COLD = cooling-sensitive thermoreceptive-specific cells; HPC = heat-pinch-cold polymodal nociceptive cells; NS = nociceptive cells; PAG = periaqueductal gray; PB = parabrachial nucleus; STT = spinothalamic tract. Fig. 2. Baseline coronal ( upper ) and axial ( center and lower ) T 1 -weighted MR images demonstrating a large area of encephalomalacia corresponding to a left middle cerebral artery distribution of the infarct involving the cortex, subcortical white matter, basal ganglia, and the lateral region of the

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Dzenan Lulic, Amir Ahmadian, Ali A. Baaj, Selim R. Benbadis and Fernando L. Vale

connection of the vagus is the NTS, which projects to the LC and adjacent parabrachial nucleus, dorsal raphe, nucleus ambiguus, cerebellum, hypothalamus, thalamus, insula, medullary reticular formation, and other brainstem structures, several of which are known to modulate seizures in various models. 19 , 33 By stimulating the cut end of the vagus nerve, they were able to identify an evoked response at the level of intralaminar regions of the thalamus. Through a thalamic pathway this afferent connection modified neuronal activity at the level of the cerebral cortex

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Hiroaki Saura, Takaaki Beppu, Hideki Matsuura, Shigeki Asahi, Noriyuki Uesugi, Makoto Sasaki and Kuniaki Ogasawara

horseshoe-shaped band of gray matter composed of the lateral parabrachial nucleus (PBN), the Kölliker-Fuse nucleus, and the medial PBN ( Fig. 3 upper). These nuclei receive important afferent fibers from the cardiovascular, respiratory, and gustatory systems and project efferent fibers toward superior centers. 5 On the other hand, the paraventricular nucleus (PVN), which is located in the medial hypothalamus, is a center of the autonomic nervous system and neuroendocrine system, and it is closely associated with yawning ( Fig. 3 lower). 4 , 6 An experimental study in

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Laureen D. Hachem, Simeon M. Wong and George M. Ibrahim

underlie VNS treatment effect. ACC = anterior cingulate cortex; amyg = amygdala; hyp = hypothalamus; ins = insula; PB = parabrachial nucleus; PFC = prefrontal cortex; S1 = primary somatosensory cortex; thal = thalamus. Copyright Kate Campbell, Medical & Scientific Visualizations. Published with permission. Brainstem Centers Attempts to map the underlying neural networks involved in VNS response has led to the identification of critical brainstem nuclei and neurotransmitter systems that appear to be early mediators in the pathway of seizure modulation. Nucleus Tractus

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William P. Nobis, Karina A. González Otárula, Jessica W. Templer, Elizabeth E. Gerard, Stephen VanHaerents, Gregory Lane, Guangyu Zhou, Joshua M. Rosenow, Christina Zelano and Stephan Schuele

respiratory efforts, 17 but more precise investigation is necessary to fully determine the critical pathways. The extended amygdala also provides major input to the arousal network of the brain including the serotonergic raphe nuclei 27 , 32 and the parabrachial nucleus in the pons, both of which can modulate the respiratory cycle and directly sense hypercapnia and influence arousal. 15 It is possible that the amygdala is involved in both the onset of apnea with seizures and the impairment of arousal systems. Plasticity induced by repeated seizures in this circuit, as