title: Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain.
abstract: Nerve endings in the epidermis, termed nociceptors, conduct information on noxious stimuli to the central nervous system. The precise role of epidermal nerve fibers in neuropathic pain is however still controversial. Here, we have investigated the re-innervation patterns of epidermal and dermal nerve fibers in a rat neuropathic pain model. After applying the spared nerve injury (SNI) model, we determined the mechanical and thermal withdrawal thresholds in the uninjured lateral (sural) and medial (saphenous) areas of the affected hind paw and investigated the innervations patterns of Substance P (SubP), Neurofilament-200 (NF-200) and P2X3-immunoreactive (IR) nerve fibers in the epidermis and dermis. We found a significant loss in the density of peptidergic (Sub P and NF-200) and non-peptidergic (P2X3) nerve fibers in the center area of the foot sole at 2 weeks postoperatively (PO). The densities of Sub P-IR fibers in the epidermis and upper dermis, and the density of P2X3-IR fibers in the upper dermis were significantly increased at 10 weeks PO as compared to 2 weeks PO, but were still significantly lower than the densities in controls. However, the density of NF-200-IR fibers in the center area reached control levels at 10 weeks PO. No changes were found in the densities of any of the fibers in the medial and lateral parts of the foot sole. The present results suggest that after peripheral nerve injury, specific nerve fibers have different re-innervation patterns in the epidermis and dermis and that they might be involved in the development of neuropathic pain.
authors.affiliation: Department of Neuroscience, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. l.duraku@erasmusmc.nl
authors.forename: Liron S
authors.initials: LS
authors.lastname: Duraku
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hossaini
authors.forename: Barthold N
authors.initials: BN
authors.lastname: Schüttenhelm
authors.forename: Joan C
authors.initials: JC
authors.lastname: Holstege
authors.forename: Martijn
authors.initials: M
authors.lastname: Baas
authors.forename: Tom J H
authors.initials: TJ
authors.lastname: Ruigrok
authors.forename: Erik T
authors.initials: ET
authors.lastname: Walbeehm
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D020405:Dermis / Q000473:pathology*; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology*; D006930:Hyperalgesia / Q000209:etiology; D007801:Langerhans Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009437:Neuralgia / Q000150:complications / Q000209:etiology / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; D058477:Receptors, Purinergic P2X3; C051774:neurofilament protein H; D013373:Substance P; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide