Abstract
Convergent data showed that bulbo-spinal serotonergic projections exert complex modulatory influences on nociceptive signaling within the dorsal horn. These neurons are located in the B3 area which comprises the median raphe magnus (RMg) and the lateral paragigantocellular reticular (LPGi) nuclei. Because LPGi 5-HT neurons differ from RMg 5-HT neurons regarding both their respective electrophysiological properties and responses to noxious stimuli, we used anatomical approaches for further characterization of the respective spinal projections of LPGi versus RMg 5-HT neuron subgroups.Adult Sprague-Dawley rats were stereotaxically injected into the RMg or the LPGi with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The precise location of injection sites and RMg vs LPGi spinal projections into the different dorsal horn laminae were visualized by PHA-L immunolabeling. Double immunofluorescent labeling of PHA-L and the serotonin transporter (5-HTT) allowed detection of serotonergic fibers among bulbo-spinal projections.Anterograde tracing showed that RMg neurons project preferentially into the deep laminae V-VI whereas LPGi neuron projections are confined to the superficial laminae I-II of the ipsilateral dorsal horn. All along the spinal cord, double-labeled PHA-L/5-HTT immunoreactive fibers, which represent only 5–15% of all PHA-L-immunoreactive projections, exhibit the same differential locations depending on their origin in the RMg versus the LPGi.The clear-cut distinction between dorsal horn laminae receiving bulbo-spinal serotonergic projections from the RMg versus the LPGi provides further anatomical support to the idea that the descending serotonergic pathways issued from these two bulbar nuclei might exert different modulatory influences on the spinal relay of pain signaling neuronal pathways.
Highlights
The rostral ventromedial medulla (RVM), which comprises the serotonergic region B3 with serotonin (5-hydroxytryptamine, 5HT) - containing perikarya in the raphe magnus nucleus (RMg) and the lateral paragigantocellular reticular nucleus (LPGi), is known to play an important role in the bulbo-spinal descending control of nociceptive messages (Fields and Basbaum, 1978; Besson and Chaouch, 1987; Millan, 2002)
Typical Phaseolus vulgaris leucoagglutinin (PHA-L) immunolabeling after injection into the RMg or the LPGi is illustrated in Fig. 1B1 and 1B2, respectively
We focused on the respective projections from the RMg and the LPGi nuclei, two structures in the B3 region which were previously shown to contain serotonergic neurons innervating the spinal cord (Fields and Basbaum, 1978; Besson and Chaouch, 1987)
Summary
The rostral ventromedial medulla (RVM), which comprises the serotonergic region B3 with serotonin (5-hydroxytryptamine, 5HT) - containing perikarya in the raphe magnus nucleus (RMg) and the lateral paragigantocellular reticular nucleus (LPGi), is known to play an important role in the bulbo-spinal descending control of nociceptive messages (Fields and Basbaum, 1978; Besson and Chaouch, 1987; Millan, 2002). Novel shRNA interference approaches to selectively deplete 5-HT in these pathways provided clear-cut demonstration of 5-HT-mediated bulbo-spinal modulations of both acute and chronic pain in rats (Wei et al, 2010; Gautier et al, 2017), in convergence with a recent report on the effectiveness of selective optogenetic activation of RVM-serotonergic neurons to markedly affect pain signaling in rats (Cai et al, 2014). In spite of such a large body of studies devoted to unveil the actual role of bulbo-spinal serotonergic pathways in the control of pain signaling, the situation is still confused to date. Some authors (Suzuki et al, 2004; Rahman et al, 2006; Wei et al, 2010; Guo et al, 2014) concluded that these pathways are implicated in pain promoting mechanisms whereas others (Yamazaki et al, 1999; Hung et al, 2003; Gencer et al, 2015; Lee et al, 2015) reached the opposite conclusion, i.e. these pathways exerting an inhibitory influence on pain signaling
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