Projections from the nociceptive area of the central nucleus of the amygdala to the forebrain: a PHA-L study in the rat.

The lateral capsular division (CeLC) of the central nucleus (Ce) of the amygdala, in the rat, has been shown to be the main terminal area of a spino(trigemino)-parabrachio-amygdaloid nociceptive pathway [Bernard & Besson (1990) J. Neurophysiol. 63, 473-490; Bernard et al. (1992) J. Neurophysiol. 68, 551-569; Bernard et al. (1993) J. Comp. Neurol. 329, 201-229]. The projections to the forebrain from the CeLC and adjacent regions were studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L) restricted in subdivisions of the Ce and the basolateral amygdaloid nucleus anterior (BLA). Our data showed that the entire CeLC projects primarily and extensively to the substantia innominata dorsalis (SId). The terminal labelling is especially dense in the caudal aspect of the SId. The other projections of the CeLC in the forebrain were dramatically less dense. They terminate in the bed nucleus of the stria terminalis (BST) and the posterior hypothalamus (pLH). No (or only scarce) other projections were found in the remaining forebrain areas. The Ce lateral division (CeL) and the Ce medial division (CeM), adjacent to the CeLC, also project to the SId with slightly lower density labelling. However, contrary to the case of the CeLC, both the CeL and the CeM extensively project to the ventrolateral subnucleus of the BST (BSTvl) with a few additional terminals found in other regions of the lateral BST. Only the CeM projects densely to both the interstitial nucleus of the posterior limb of the anterior commissure and the caudal most portion of the pLH. The projections of the BLA are totally different from those of the Ce as they terminate in the dorsal striatum, the accumbens nucleus, the olfactory tubercle, the nucleus of olfactory tract and the rostral pole of the cingulate/frontal cortex. This study demonstrates that the major output of the nociceptive spino(trigemino)-parabrachio-CeLC pathway is to the SId. It is suggested that the CeLC-SId pathway could have an important role in anxiety, aversion and genesis of fear in response to noxious stimuli.

Parabrachial internal lateral neurons convey nociceptive messages from the deep laminas of the dorsal horn to the intralaminar thalamus.

This study investigates the physiological properties of parabrachial internal lateral (PBil) neurons that project to the paracentral thalamic (PC) nucleus using antidromic activation and single-unit recording techniques in anesthetized rat. We reported here that most of these neurons responded exclusively to the nociceptive stimulation of large receptive fields with a sustained firing that often outlasted the stimulus up to several minutes. These responses were depressed by intravenous morphine. Our results demonstrated a novel spino-PBil-PC pathway, which transmits nociceptive messages to the PC nucleus, which in turn projects to the prefrontal cortex. Recent clinical imaging studies showed the important participation of prefrontal cortex in emotional response to pain. This spino-PBil-PC pathway may explain how nociceptive messages reach the prefrontal cortex and thus trigger unbearable aversive aspects of pain.

Ventromedial thalamic neurons convey nociceptive signals from the whole body surface to the dorsolateral neocortex.

The somatosensory properties of ventromedial (VM) thalamic neurons were investigated in anesthetized rats by examining their responses to calibrated cutaneous stimuli. A population of neurons within the lateral part of the ventromedial thalamus (VMl) showed two peaks of activation after percutaneous electrical stimuli, regardless of which part of the body was stimulated. The early and late peaks were elicited by Adelta- and C-fiber activities with mean conduction velocities of 12.9 +/- 0.9 and 1 +/- 0.2 m/sec, respectively. These responses were strongly depressed or blocked after microinjections within the medullary subnucleus reticularis dorsalis of xylocaine or the NMDA antagonist MK-801. None of the VMl neurons responded to innocuous cutaneous or proprioceptive stimuli. In contrast, all these neurons responded to noxious mechanical and thermal stimulation of the limbs and showed monotonic increases in their discharges to increasingly strong noxious cutaneous stimuli. In addition, some VMl neurons were antidromically activated by stimulation in layer I of the dorsolateral frontal cortex. These findings suggest that the rat VMl conveys and encodes cutaneous nociceptive inputs from any part of the body surface to layer I of the dorsolateral neocortex. This reticulo-thalamo-cortical network may allow any signal of pain to gain access to widespread areas of the neocortex and thus help prime the cortex for attentional reactions and/or the coordination of motor responses.

Differential projections to the intralaminar and gustatory thalamus from the parabrachial area: a PHA-L study in the rat.

The organization of projections from the parabrachial (PB) area to the ventral posterior parvicellular (VPpc) "gustatory" and intralaminar nuclei of the thalamus was studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L), into subregions of the PB area. The present study is a follow-up of three former studies (Bernard et al. [1993] J. Comp. Neurol. 329:201-229; Aldén et al. [1994] J. Comp. Neurol. 341:289-314; Bester et al. [1997a] J. Comp. Neurol. 383:245-281) that examined PB projections onto the amygdala, the bed nucleus of the stria terminalis, and the hypothalamus. Our data showed that (1) the region centered in the internal lateral PB subnucleus projects densely with a bilateral and symmetric pattern to the caudal portion of the paracentral and, to a lesser extent, to the adjacent portion of the central and parafascicular medial thalamic nuclei; (2) the mesencephalic PB region centered in the ventral lateral subnucleus and scattered neurons in the subjacent brachium conjunctivum project primarily, although diffusely, to the central medial thalamic nucleus. The third region includes two subgroups: (3a) the medial subgroup, including the medial, the waist area, and the ventral lateral subnuclei of the pontine PB area, projects bilaterally but with a weak ipsilateral predominance to the VPpc, terminals bearing large varicosities. Additionally, a diffuse projection with small varicosities spreads in the area between the two VPpc nuclei and the central medial nucleus. (3b) The lateral subgroup, centered in the external medial subnucleus, projects with a contralateral predominance in the periphery of the VPpc nuclei, most terminals being located around the dorsomedial tip. It is suggested that the PB projections to the intralaminar nucleus could be involved in cortical limbic arousal processing in relation with nociceptive, (somatic, visceral, and intraoral) and gustatory aversive stimuli. The projection with large varicosities inside the VPpc could process gustatory discrimination.