Regeneration of primary sensory axons into the adult rat spinal cord via a peripheral nerve graft bridging the lumbar dorsal roots to the dorsal column.

Abstract

This study investigated the feasibility of using a peripheral nerve autograft (NAG) to promote and guide regeneration of sensory axons from the caudal lumbar dorsal roots to the rostral dorsal column following a lower thoracic cordotomy in adult rats. After a left hemicordotomy at the T13 vertebra level and ipsilateral L3 and L4 rhizotomies, a peripheral NAG (peroneal nerve) was connected to the distal roots stumps, then implanted into the left dorsal column 10 mm rostral to hemicordotomy site (n = 12). After surgery, all animals of the experimental group experienced complete anesthesia in their left hindlimb. Three months later, a slight response to nociceptive stimulation reappeared in L3 and/or L4 dermatomes in 6 of the 12 experimental animals. None of these animals exhibited self-mutilation. Nine months after surgery, we performed retrograde tracing studies by injecting horseradish peroxidase (HRP) into the left dorsal column 30 mm rostral to the NAG implantation site. In eight animals, we found HRP-stained neurons in the left L3 and/or L4 dorsal root ganglia (DRG). The mean number of HRP-stained neurons per DRG was 71 +/- 92 (range 2-259). In control groups, no HRP-stained neurons were found in L3 or L4 DRG. Histological analysis of the NAG showed evidence of axonal regeneration in all 8 animals with positive retrograde labeling of DRG neurons. However, we did not find a statistical correlation between the number of HRP-stained neurons and the degree of sensory recovery. This study demonstrates that an NAG joining dorsal roots to the dorsal column, thus shunting the original CNS-PNS junction, can support regeneration of central axons from DRG primary sensory neurons into the dorsal column over distances of at least 30 mm despite the inhibitory influence of the CNS white matter.