Increased Calcitonin Gene-Related Peptide Immunoreactivity in Gracile Nucleus after Partial Sciatic Nerve Injury: Age-Dependent and Originating from Spared Sensory Neurons

Abstract

Following a unilateral chronic constriction injury of the sciatic nerve, calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fiber density increases in the ipsilateral gracile nucleus, and this is more pronounced in aged (16-month) rats where the fibers are dystrophic. In this study we show that a second type of partial sciatic nerve injury, a half-transection, also induces CGRP-IR fibers in the gracile nucleus, but this effect is strongly age-dependent, being much more pronounced in 8- to 10-month-old rats than in 2- to 3-month-old rats. Dystrophic CGRP-IR fibers were rarely observed in 8- to 10-month-old animals, so the increased reaction in aged animals and axonal dystrophy are separate phenomena. Using double-labeling with fluorescent dye tracing for 8- to 10-month-old rats, we showed that neuron profiles in the dorsal root ganglion (DRG) with peripheral axons spared by the partial sciatic nerve injury were 10 times more likely to be CGRP mRNA-positive than profiles with injured peripheral axons, suggesting that spared neurons are more likely to contribute to the increase in CGRP-IR fibers in the gracile nucleus. Using combined fluorescent dye tracing with in situ hybridization for CGRP mRNA or CGRP immunostaining, we further showed that CGRP-expressing DRG neuron profiles with central projections to the gracile nucleus had peripheral axons spared by the partial nerve injury. We conclude that the increased CGRP immunoreactivity in the gracile nucleus following partial sciatic nerve injury originates from primary sensory neurons with axons spared by the injury. These neurons may still transmit cutaneous sensory information and thus the increased CGRP immunoreactive fibers in the gracile nucleus may be involved in the mechanical allodynia characteristic of neuropathic pain syndromes following partial nerve injury.