Rea, Paul Michael
The role of the lateral spinal nucleus in nociception.
PhD thesis, University of Glasgow.
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The lateral spinal nucleus (LSN), located in the dorsolateral funiculus, is an area that has been poorly understood, but has been implicated in nociception. To investigate the function of this nucleus, three broad areas were investigated: responses to nociceptive stimuli, neurochemical relations to the NK-1 receptor, and projections from this nucleus to several brain centres, to try to gain a greater understanding of the functions of this nucleus. The following conclusions can be drawn from the studies undertaken here:
• A series of double-labelling experiments for confocal microscopy were carried out in the rat (Sprague-Dawley) to investigate the LSN responses to a variety of peripheral cutaneous noxious stimuli. It was found that the LSN responds to both thermal and chemical peripheral cutaneous noxious stimulation. However, unlike as previously thought, only a small number of neurons in the LSN are activated by a peripheral noxious stimulus, with hot water (55°C applied to the hind-paw) activating the most, as revealed by Fos immunoreactivity. Only 15% of LSN neurons showed response to this peripheral noxious stimulus. Interestingly, unlike the superficial dorsal horn (SDH), bilateral activation of LSN neurons after the application of a peripheral noxious stimulus was found in most of the experiments carried out.
• Triple and quadruple-labelling experiments for confocal microscopy were carried out in the rat to investigate neurochemical relations at this site. It was found that although the LSN is abundant in staining for substance P, the number of LSN neurons showing immunoreactivity for the target of substance P (the NK-1 receptor) represented only one-third of all neurons at this site. However, substance P and nitric oxide synthase were associated with NK-1 neurons, and specifically nitric oxide synthase terminals were preferentially associated with NK-1 neuronal cell bodies. However, unlike the superficial dorsal horn, nitric oxide synthase terminals were not associated with inhibitory GABAergic neurons.
• Using retrograde injection techniques (in the rat) combined with multiple immunolabelling for confocal microscopy, the LSN was shown to project to areas traditionally associated with nociception (caudal ventrolateral medulla and mediodorsal thalamus) but also projected to the hypothalamus and also the lateral globus pallidus. Indeed, the regions found to have the most projections from the LSN were the lateral and medial hypothalamus, with most of those neurons (>80%) possessing the NK-1 receptor. Interestingly, although numbers of retrogradely labelled neurons were low, they represented 30% of all labelled neurons that projected from the LSN to the lateral globus pallidus.
In conclusion, the extent of involvement of the LSN in nociception is less than previously thought, but with projections to the hypothalamus, it could be postulated that the LSN functions as an integrative nucleus for autonomic and homeostatic functions, and related motivational and affective responses to autonomic function.
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