This review presents a schematic attempt to classify the major pain pathways, based on the results of recent studies in our laboratory, with a special emphasis on the parabrachial system. Our view is based on results from experiments in the rat, using very small iontophoretic injections of anterograde tracers. As illustrated in this report, we have found a very dramatic difference between ascending projections originating from deep laminae compared with those arising from lamina I of the dorsal horn. We propose three main pain systems and discuss their functional‐anatomical relationships. The first system is centred on the projection from deep laminae to three caudal reticular areas – the lateral reticular nucleus (LRN), the subnucleus reticularis dorsalis (SRD) and the gigantocellular lateral paragigantocellular reticular nuclei (NGc) – and the parabrachial internal lateral subnucleus (PBil). The second system is centred on the projection from lamina I to the ventral posterolateral nucleus (VPL), the ventral posteromedial (VPM), the posterior nuclear group (Po) and triangular posterior nucleus (PoT) of the thalamus. The third system is centred on the projection from lamina I to the lateral parabrachial area. We also present the four main projections from the latter area to the extended amygdala, the hypothalamus, the periaqueductal grey matter (PAG), and the ventrolateral medulla (VLM), and their involvement in emotional and autonomic (homeostatic) aspects of pain.
Projections to the forebrain from lamina I of spinal and trigeminal dorsal horn were labeled anterogradely with Phaseolus vulgaris-leucoagglutinin (PHA-L) and/or tetramethylrhodamine-dextran (RHO-D) injected microiontophoretically. Injections restricted to superficial laminae (I/II) of dorsal horn were used primarily. For comparison, injections were also made in deep cervical laminae. Spinal and trigeminal lamina I neurons project extensively to restricted portions of the ventral posterolateral and posteromedial (VPL/VPM), and the posterior group (Po) thalamic nuclei. Lamina I also projects to the triangular posterior (PoT) and the ventral posterior parvicellular (VPPC) thalamic nuclei but only very slightly to the extrathalamic forebrain. Furthermore, the lateral spinal (LS) nucleus, and to a lesser extent lamina I, project to the mediodorsal thalamic nucleus. In contrast to lamina I, deep spinal laminae project primarily to the central lateral thalamic nucleus (CL) and only weakly to the remaining thalamus, except for a medium projection to the PoT. Furthermore, the deep laminae project substantially to the globus pallidus and the substantia innominata and more weakly to the amygdala and the hypothalamus. Double-labeling experiments reveal that spinal and trigeminal lamina I project densely to distinct and restricted portions of VPL/VPM, Po, and VPPC thalamic nuclei, whereas projections to the PoT appeared to be convergent. In conclusion, these experiments indicate very different patterns of projection for lamina I versus deep laminae (III-X). Lamina I projects strongly onto relay thalamic nuclei and thus would have a primary role in sensory discriminative aspects of pain. The deep laminae project densely to the CL and more diffusely to other forebrain targets, suggesting roles in motor and alertness components of pain.
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.
This study investigated the responses of posterior triangular (PoT) thalamic neurons to tactile and noxious calibrated stimuli in anesthetized rats. We report here that 41% of PoT units responded to cutaneous stimulation, in most cases, by increasing strongly their firing. Forty-five percent of the responding units were nociceptive specific (NS), 19% were nociceptive nonspecific (NNS), and 36% were tactile. The NS units responded only to frankly noxious stimuli applied to relatively large receptive fields (several parts of the body). They encoded nociceptive temperatures chiefly in 46 -50°C ranges. The NNS units resembled NS units but also responded to innocuous stimuli. Tactile units responded chiefly to repeated innocuous stimuli applied to very small receptive fields (one to two fingers or vibrissae).A representative sample of PoT somatosensory neurons, characterized first by their response to innocuous and noxious cutaneous stimuli, were filled with juxtacellular injection of biotin-dextran that made it possible to label adequately the soma, the dendrites, and the entire axon of PoT neurons. We observed that the axons of NS neurons terminated only in secondary somatosensory (S2) cortex, whereas the axons of NNS and tactile neurons projected chiefly to the insular cortex and the amygdala.In conclusion, our results demonstrate a spinal-PoT-S2/insular cortices nociceptive pathway that conveys nociceptive messages arising from lamina I and spinal neurons of deep laminas. Furthermore, our results demonstrate for the first time that projections of PoT neurons are correlated to their physiological properties.
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