An intact intermediate filament network is required for collateral sprouting of small diameter nerve fibers.

Expression of the intermediate filament (IF) protein peripherin is initiated during development at the time of axonal extension and increases during regeneration of nerve fibers. To test whether the IF network is essential for neuron process outgrowth in the mature organism in vivo, we disrupted endogenous peripherin IF in small-sized dorsal root ganglion (DRG) neurons in transgenic mice via expression of a mutant peripherin transgene under control of peripherin gene regulatory sequences. Anatomical and functional analyses showed that these neurons send peripheral and central axonal projections to correct targets, express correct neuropeptides, and mediate acute pain responses normally. However, disruption of IF significantly impaired the ability of uninjured small-sized DRG neurons to sprout collateral axons into adjacent denervated skin, indicating a critical role for intact IF in plasticity, specifically in compensatory nociceptive nerve sprouting.