Induction of intramuscular collateral nerve sprouting by neurally applied colchicine

Abstract

The plantaris muscle of the rat is innervated by fibers deriving from spinal nerves L4 and L5. When L4 is transected, the intact residual L5 fibers sprout intramuscular preterminal processes which reinnervate some of the denervated muscle fibers and restore their weight and strength. Experiments by Diamond and his colleagues on cutaneous innervation in salamanders indicated that collateral sprouting can be elicited by applying colchicine to a nerve as well as by transecting it, and it therefore seems that collateral sprouting results from the interruption of axonal transport rather than from nerve degeneration. We tested this hypothesis by either transecting or applying colchicine to spinal nerve L4 in the rat and measuring the isometric strength of contraction of the plantaris 2 weeks later. After transection of L4, electrical stimulation of L4 gave no response whereas stimulation of L5 gave a supranormal isometric tension; after application of colchicine to L4, stimulation of L4 resulted in a normal isometric tension and stimulation of L5 gave a supranormal one. The muscles were examined histologically by combined silver-cholinesterase staining. Colchicine treatment produced abnormalities of innervation pattern characteristic of preterminal collateral sprouting. Because colchicine disrupts axonal transport, we interpret these results to mean that interruption of axonal transport in L4 fibers stimulates intramuscular sprouting of L5 fibers. The data are consistent with Diamond's hypothesis that nerves possess a propensity for collateral growth which is ordinarily repressed by factors that are dependent on axonal transport.