Unilateral nerve injury produces bilateral loss of distal innervation

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Abstract
There are no known anatomical connections between neurons that innervate homologous right and left body parts. Nevertheless, some patients develop bilateral abnormalities after unilateral injury, a phenomenon often unrecognized and not yet characterized. Therefore, we examined in rats the effects of ligating and cutting one tibial nerve on sensory function and on density of innervation in hind paws contralaterally as well as ipsilaterally to the injury, at times between 1 day and 5 months after surgery. Punches removed from tibial‐ or sural‐innervated planter paw skin were immunolabeled to quantitate epidermal nerve endings. Naive and sham‐operated rats provided controls. Axotomized rats had near‐total loss of PGP9.5+ innervation within ipsilateral tibial‐innervated skin at all time‐points. Adjacent ipsilateral sural‐innervated skin had persistent hyperalgesia without denervation, and robust axonal sprouting at 5 months after surgery. Contralesional hind paws lost 54% of innervation in tibial‐innervated epidermis starting 1 week after surgery and persisting throughout. Contralesional sural‐innervated skin had neither neurite loss nor sprouting. These results imply that unilateral nerve injury can cause profound, long lasting, nerve–branch–specific loss of distal innervation contralaterally as well as ipsilaterally. They discredit the practice of using tissues contralateral to an injury to provide normative controls and suggest the possibility of rapid, transmedian postinjury signals between homologous mirror‐image neurons.