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The Journal of Neuroscience, October 22, 2003, 23(29):9491-9499

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Behavioral/Systems/Cognitive
Lack of Evidence for Sprouting of A Afferents into the Superficial Laminas of the Spinal Cord Dorsal Horn after Nerve Section

David I. Hughes, Dugald T. Scott, Andrew J. Todd, and John S. Riddell

Spinal Cord Group, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom

The central arborizations of large myelinated cutaneous afferents normally extend as far dorsally as the ventral part of lamina II in rat spinal cord. Woolf et al. (1992) reported that after nerve injury some of these afferents sprouted into lamina I and the dorsal part of lamina II, and it has been suggested that this could contribute to allodynia associated with neuropathic pain. Part of the evidence for sprouting was on the basis of the use of cholera toxin B subunit as a selective tracer for A-fibers, and the validity of this approach has recently been questioned; however, sprouting was also reported in experiments involving intra-axonal labeling of chronically axotomized afferents.

We have used intra-axonal labeling in the rat to examine central terminals of 58 intact sciatic afferents of presumed cutaneous origin and 38 such afferents axotomized 7-10 weeks previously. Both normal and axotomized populations included axons with hair follicle afferent-like morphology and arbors that entered the ventral half of lamina II; however, none of these extended farther dorsally. We also performed bulk labeling of myelinated afferents by injecting biotinylated dextran into the lumbar dorsal columns bilaterally 8-11 weeks after unilateral sciatic nerve section. We observed that both ipsilateral and contralateral to the sectioned nerve, arbors of axons with hair follicle afferent-like morphology in the sciatic territory extended only as far as the ventral half of lamina II. Therefore these results do not support the hypothesis that A afferents sprout into the superficial laminas after nerve section.

Key words: neuropathic pain; allodynia; nerve injury; myelinated afferent; low-threshold mechanoreceptor; intra-axonal injection

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Received June 30, 2003; revised August 29, 2003; accepted August 29, 2003.

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