Regeneration of Primary Sensory Neurons

Abstract

Primary sensory neurons have an inherent capacity for regeneration of their cut, crushed, or chemically lesioned axons. This capacity is displayed to a much greater extent after lesions of the peripheral axons than after lesions of their centrally directed axons. Additionally, the surrounding tissue determines to a significant extent the degree of recovery: whereas the peripheral nerve tissue provides neurotrophic support and a favorable environment for axonal growth, the central terminals of primary sensory neurons face a non-permissive and inhibitory glial tissue. Mechanical lesions of the peripheral axons of dorsal root ganglion (DRG) sensory neurons can be repaired by the intrinsic regenerative capacity of the neuron itself, when outgrowing axons from the proximal stump are able to transverse the tissue scar and reach the distal stump of the nerve. Bridging the gap with an autologous nerve graft or a short artificial graft filled with nerve growth factor (NGF) can improve recovery. Neurotoxic lesions of the axon terminals are effectively recovered by intermittent local or systemic NGF injections. A recovery from a diabetic sensory neuropathy probably requires the continuous delivery of NGF or additional neurotrophic factors. A recovery from a dorsal rhizotomy or from a dorsal column lesion can possibly be achieved by the concomitant transgene-mediated overexpression of neurotrophins, the transformation of the DRG neuron cells to a competence for regrowth, and the counteraction of the growth-inhibitory nature of the central nervous system tissue.

ERK and STAT3 Phosphorylation in Sensory Neurons during Capsaicin-Induced Impairment and Nerve Growth Factor Treatment

“…The slow recovery of the amount of phosphorylated ERK between day 8 and day 16 points towards a spontaneous regeneration process. These processes have already been proposed previously to occur after a capsaicin denervation [1,17] . The ERK pathway would seem particularly necessary for regeneration of sensory neurons and for morphological responses like axon extension [7,14] .…”

“…In the following 8 days phospho-ERK decreased to very low levels and was found recovered to basal values at the time point 16 days. An additional intraplantar nerve growth factor (NGF) injection at time points 20, 44 and 92 h after the capsaicin treatment, and collection of tissues 4 h later, markedly increased the level of phospho-ERK in the sciatic nerve as well as in the DRG, as compared to the samples taken from rats at the same time tochemical parameters [1] . In adult rats a systemic treatment with a large dose of capsaicin is known to induce a neurochemical lesion of the terminal axons of sensory C and A ␦ fi bers without destroying the cell bodies of these neurons in the dorsal root ganglia (DRG) [2] .…”

Bidirectional Interactions between H-Channels and Na+–K+Pumps in Mesencephalic Trigeminal Neurons

“…This further suggests an involvement of the cell body of MTN neurons in the control of its firing activity together with the integration of various synaptic inputs (Copray et al, 1990;Kolta et al, 1993), independent of impulses arising from peripheral mechanoreceptors. This is in contrast to the function of the cell body of other primary sensory neurons that is involved in the regulation of axon growth during development (Zhang et al, 1994;Snider and Silos-Santiago, 1996) and in regeneration or maintenance of axons (Bergman et al, 1999;Donnerer, 2003), through activation of neurotrophin receptors.…”

Differential Regulation of 3-Beta-Hydroxysteroid Dehydrogenase and Vanilloid Receptor TRPV1 mRNA in Sensory Neurons by Capsaicin and NGF

“…The peripheral sensory neurons comprise a class of neurons which are subject to a number of neurochemical adaptations following their selective lesion by capsaicin and their regeneration [1,2]. It has been shown that in adult rats the unmyelinated and thinly myelinated sensory C-and A‰-fibers connected to small sensory neurons degenerate at their terminal region in response to a capsaicin treatment, and that a process of spontaneous recovery is initiated [3,4].…”