Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-1
pubmed:abstractText
Keratinocytes play an important role in the dialog between skin and cutaneous sensory neurons. They are an essential source of cutaneous nerve growth factor (NGF), a neurotrophin that contributes to persistent pain in inflammation and neuropathy. We studied the interaction of human keratinocytes (hKTs) and regenerating afferent nerve fibers by transplanting hKTs into a ligated and transected peripheral nerve. The hKTs self-assembled into a multi-laminar spheroid cellular structure resembling the stratum spinosum of epidermis. Axonal sprouts surrounded the structure although they were excluded from entry. Levels of NGF were elevated at the transplant site. Whole cell patch-clamp recordings from primary afferent neurons whose cut axons were present near the transplanted hKTs displayed extreme hyperexcitability. These neurons generated high frequency trains of action potentials during step depolarization stimuli, and they sometimes showed afterdischarge and fired spontaneously at resting membrane potential. This spontaneous firing originated from subthreshold membrane potential oscillations. The animals with the hKT transplants exhibited spontaneous pain behavior manifest as autotomy. The results demonstrate that an interaction between injured/regenerating nerve fibers and keratinocytes such as may occur during wound healing, results in afferent hyperexcitability and pain. These results have implications for persistent pain associated with burn and traumatic skin injuries.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-6623
pubmed:author
pubmed:copyrightInfo
Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
148
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
94-102
pubmed:meshHeading
pubmed-meshheading:19932564-Action Potentials, pubmed-meshheading:19932564-Analysis of Variance, pubmed-meshheading:19932564-Animals, pubmed-meshheading:19932564-Axons, pubmed-meshheading:19932564-Cell Transplantation, pubmed-meshheading:19932564-Cells, Cultured, pubmed-meshheading:19932564-Disease Models, Animal, pubmed-meshheading:19932564-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:19932564-Female, pubmed-meshheading:19932564-Ganglia, Spinal, pubmed-meshheading:19932564-Humans, pubmed-meshheading:19932564-Keratinocytes, pubmed-meshheading:19932564-Mice, pubmed-meshheading:19932564-Mice, Nude, pubmed-meshheading:19932564-Microscopy, Electron, Transmission, pubmed-meshheading:19932564-Nerve Fibers, Unmyelinated, pubmed-meshheading:19932564-Nerve Growth Factor, pubmed-meshheading:19932564-Neurofilament Proteins, pubmed-meshheading:19932564-Neuroma, pubmed-meshheading:19932564-Pain Measurement, pubmed-meshheading:19932564-Patch-Clamp Techniques, pubmed-meshheading:19932564-Potassium Chloride, pubmed-meshheading:19932564-Sciatica, pubmed-meshheading:19932564-Sensory Receptor Cells
pubmed:year
2010
pubmed:articleTitle
Keratinocytes acting on injured afferents induce extreme neuronal hyperexcitability and chronic pain.
pubmed:affiliation
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural