Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies.
We describe the expression of the capsaicin receptor (TRPV1) in human peripheral nervous system (PNS) and its changes in sural nerve and skin nerve fibers of patients with painful neuropathy. Dorsal root ganglion (DRG), root, and spinal cord autopsy specimens from subjects without PNS diseases were immunoassayed with anti-TRPV1 antibodies. Bright-field and confocal microscope studies using anti-TRPV1, protein gene product 9.5 (PGP 9.5), and unique-beta-tubulin (TuJ1) antibodies were performed in skin biopsies from 15 healthy subjects and 10 painful neuropathies. The density of intraepidermal nerve fiber (IENF) labeled by each antibody was quantified. Sural nerve biopsies from three patients with painful, one patient with nonpainful diabetic neuropathy, and two patients with multifocal motor neuropathy used as controls were immunoassayed with anti-TRPV1 antibodies and investigated by immunoelectron microscopy. TRPV1 strongly labeled laminae I and II of dorsal horns, most small-size and some medium-size DRG neurons, and small-diameter axons of dorsal roots. In sural nerve, TRPV1 was expressed within the cytoplasm of most unmyelinated and some small myelinated axons, in the muscular lamina of epineural vessels, and in the endothelium of endoneurial vessels. The density of IENF labeled by TRPV1, PGP 9.5, and TuJ1 did not differ. TRPV1 colocalized with TuJ1 in all IENF and dermal nerve bundles. Painful neuropathies showed a diffuse loss of TRPV1-positive axons both in the sural nerve and in the skin. Our findings demonstrated that TRPV1 is normally expressed throughout the nociceptive pathway of PNS and that TRPV1-positive peripheral nerve fibers degenerate in painful neuropathies.
Lauria
Giuseppe
G
Neuromuscular Diseases, National Neurological Institute 'Carlo Besta', Milan, Italy. glauria@istituto-besta.it
Morbin
Michela
M
Lombardi
Raffaella
R
Capobianco
Raffaella
R
Camozzi
Francesca
F
Pareyson
Davide
D
Manconi
Mauro
M
Geppetti
Pierangelo
P
D000328:Adult; D000368:Aged; D001706:Biopsy / Q000379:methods; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism / Q000648:ultrastructure; D017933:Peripheral Nervous System / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000294:innervation / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D050916:TRPV Cation Channels / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014404:Tubulin; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase