title: Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord.
abstract: Peripheral axotomy-induced sprouting of thick myelinated afferents (A-fibers) from laminae III-IV into laminae I-II of the spinal cord is a well-established hypothesis for the structural basis of neuropathic pain. However, we show here that the cholera toxin B subunit (CTB), a neuronal tracer used to demonstrate the sprouting of A-fibers in several earlier studies, also labels unmyelinated afferents (C-fibers) in lamina II and thin myelinated afferents in lamina I, when applied after peripheral nerve transection. The lamina II afferents also contained vasoactive intestinal polypeptide and galanin, two neuropeptides mainly expressed in small dorsal root ganglion (DRG) neurons and C-fibers. In an attempt to label large DRG neurons and A-fibers selectively, CTB was applied four days before axotomy (pre-injury-labelling), and sprouting was monitored after axotomy. We found that only a small number of A-fibers sprouted into inner lamina II, a region normally innervated by C-fibers, but not into outer lamina II or lamina I. Such sprouts made synaptic contact with dendrites in inner lamina II. Neuropeptide Y (NPY) was found in these sprouts in inner lamina II, an area very rich in Y1 receptor-positive processes. These results suggest that axotomy-induced sprouting from deeper to superficial layers is much less pronounced than previously assumed, in fact it is only marginal. This limited reorganization involves large NPY immunoreactive DRG neurons sprouting into the Y1 receptor-rich inner lamina II. Even if quantitatively small, it cannot be excluded that this represents a functional circuitry involved in neuropathic pain.
authors.affiliation: Laboratory of Sensory System, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Bao
authors.forename: Hui Fredrik
authors.initials: HF
authors.lastname: Wang
authors.forename: Hai-Jiang
authors.initials: HJ
authors.lastname: Cai
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Tong
authors.forename: Shan-Xue
authors.initials: SX
authors.lastname: Jin
authors.forename: Ying-Jin
authors.initials: YJ
authors.lastname: Lu
authors.forename: Gunnar
authors.initials: G
authors.lastname: Grant
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000344:Afferent Pathways / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009409:Nerve Crush; D009413:Nerve Fibers, Myelinated / Q000502:physiology* / Q000648:ultrastructure; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D020671:Posterior Horn Cells / Q000502:physiology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology / Q000601:surgery; D013126:Spinal Nerve Roots / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D016900:Neurofilament Proteins; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C051774:neurofilament protein H; D002772:Cholera Toxin