Tactile mechanical allodynia is thought to be mediated by Ap-fiber afferents.146 However, the mechanisms by which this occurs are yet to be fully understood. Several studies using bulk labeling and single afferent fiber-filling techniques have demonstrated that following a peripheral nerve lesion, the central axons of injured Ap-fibers sprout from their normal termination sites in the deeper laminae of the dorsal horn (laminae II and IV) into lamina II of the dorsal horn, which is normally restricted to C-fiber and A8 nociceptors.
This synaptic rearrangement means that second-order dorsal horn neurons that normally receive predominantly high threshold sensory input, now receive inputs from low threshold mechano-receptors. Such misinterpretation of information within the spinal cord may result in low threshold sensory information being interpreted as nociceptive, leading to the emergence of hypersensitivity after peripheral nerve injury. The outgrowth of central Ap-fiber terminals is prevented by NGF and GDNF treatment, presumably by provision of trophic support for damaged C-fibers, suggesting an important role for neurotrophins in the regulation of this manifestation of structural plasticity.149 However, some studies have raised concerns about the specificity of bulk-labeling techniques and the sampling of intracellular labeled intact and injured afferents,150,151 such that the labeling may actually be due to damaged C-fibers abnormally taking up the label. However, in favor of the sprouting theory, stimulation of Ap-fibers in injured nerves can produce activation of neurons in lamina II measured electrophysiologically and by expression of c-Fos.152153 Nevertheless, further work is required to resolve the basis for the differences in these anatomical studies, and to determine the extent to which sprouting of Ap-fibers contributes to tactile hypersensitivity after peripheral nerve injury.
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