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To clarify the possible role of nitric oxide (NO) induced in primary sensory neurons after peripheral axotomy, NO synthase (NOS) immunohistochemistry was carried out on rat L5 dorsal root ganglia after sciatic nerve ligation. The results were compared with the expression of 27-kDa heat shock protein (HSP27), a neuroprotective molecule. In intact animals, NOS-immunoreactive neurons represented about 2% of all dorsal root ganglion (DRG) neurons, whereas HSP27-immunoreactive neurons comprised about 14%. After sciatic nerve ligation, both neurons increased, in number and immunoreactivity, reaching a maximum at 2 weeks, when NOS- and HSP27-immunoreactive neurons represented about 33 and 66%, respectively. NOS-immunoreactive neurons then remained unchanged until 7 weeks although HSP27-immunoreactive neurons showed a slight decline. The increased NOS-immunoreactive neurons were preferentially small (100-500 microm(2)) and coexpressed with HSP27 (about 87%). On the other hand, in the proximal stump of sciatic nerves, numerous NOS-immunoreactive fibers with a regenerative profile appeared transiently (2-4 weeks). At higher magnification, an axonal sprout from the NOS-immunoreactive small DRG neurons was found to form a basket-like structure (or basket) mostly around the cell body of NOS-negative large neurons. Retrograde labeling with a fluorescent tracer showed that both neurons sent peripheral axon collaterals to the sciatic nerve. The appearance of this unique structure was most prominent after depletion of the NOS-immunoreactive regenerating fibers in the sciatic nerve (at 7-9 weeks). The findings suggest that NO might be involved in not only axonal regeneration but also the rewiring of two classes of DRG neurons after peripheral nerve injury.

The occurrence of nitric oxide synthase-containing axonal baskets surrounding large neurons in rat dorsal root ganglia after sciatic nerve ligation