Excitatory Dorsal Horn Research Articles

Effects of an acute muscle nerve section on the excitability of dorsal horn neurones in the rat

A previous study of this laboratory showed that an acute myositis (which is associated with increased activity in slowly conducting muscle afferent fibres) is followed by marked excitability changes in the dorsal horn within a few hours. The present work addresses the question as to how the responsiveness of dorsal horn neurones changes when the same muscle nerve is transected. In anaesthetized rats, an axotomy of the gastrocnemius-soleus (GS) muscle nerves was performed and the electrical and mechanical excitability of single dorsal horn neurones in the lumbar spinal cord determined 2–8 h after the lesion. Axotomy led to a decrease in the proportion of neurones responding to A-fibre input from the cut nerve and to an increase in the efficacy of sural and peroneal nerve stimulation. The change in GS input became significant only 5–8 h after the lesion and could reflect the beginneing of neuroplastic changes. The change in sural and peroneal input was most marked 2–5 h after axotomy and is probably due to fast neuronal processes. The efficacy of C-fibre input from the sural and peroneal nerves increased significantly in the lateral dorsal horn only. In comparison with the effects of an acute myositis, the axotomy had opposite effects with regard to the GS input, but similar effects with regard to the C-fibre drive from the other nerves. It is concluded that transection of a muscle nerve is similarly effective in inducing acute changes in dorsal horn excitability as is an increase in muscle nerve activity.

Regulation of afferent connectivity in the adult spinal cord by nerve growth factor.

During development, nerve growth factor (NGF) regulates the density and character of peripheral target innervation (Barde, Neuron, 2, 1525 - 1534, 1989; Ritter et al., Soc. Neurosci. Abstr., 17, 546.2, 1991); its role in adult animals is less well defined. Here we have asked if the availability of growth factors such as NGF in peripheral tissues can influence the pattern of primary afferent connections in the CNS. Using osmotic minipumps, we raised the levels of NGF in rat skeletal muscle in vivo, a tissue where the levels of this factor are normally very low (Korsching and Thoenen, Proc. Natl. Acad. Sci. USA, 80, 3513 - 3516, 1983; Shelton and Reichardt, Proc. Natl. Acad. Sci. USA, 81, 7951 - 7955, 1984; Goedert et al., Mol. Brain Res., 1, 85 - 92, 1986). After 2 weeks of treatment we asked if the sensory neurons innervating this tissue showed an altered strength and distribution of connections with dorsal horn neurons. The contralateral (vehicle-treated) muscle, and totally untreated animals, served as controls. In normal and vehicle-treated animals, electrical stimulation of muscle afferents excited relatively few neurons in the dorsal horn, and these generally showed only weak responses. In contrast, on the NGF-treated side many more dorsal horn neurons in the lumbar enlargement of the spinal cord were excited by muscle afferents. The increased responsiveness could not be explained by a generalized increase in dorsal horn excitability, since spontaneous activity was not enhanced, nor by a change in A-fibre-mediated inhibitions from the treated afferents. Thus, these afferents appeared to establish new synaptic connections or strengthened previously weak ones as a result of increased neurotrophic factor availability. The data suggest that, in the adult rat, the levels of growth factors in peripheral targets may be used to regulate an appropriate degree of afferent connectivity within the central nervous system.