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Metalloproteinase MT5-MMP is an essential modulator of neuro-immune interactions in thermal pain stimulation

AuthorsFolgueras, Alicia R.; Llano, Elena ; Denlinger, Bristol L.; Belmonte, Carlos; Pendás, Alberto M.
Issue Date2009
PublisherNational Academy of Sciences (U.S.)
CitationProceedings of the National Academy of Sciences 106(38): 16451- 16456 (2009)
AbstractPeripheral interactions between nociceptive fibers and mast cells contribute to inflammatory pain, but little is known about mechanisms mediating neuro-immune communication. Here we show that metalloproteinase MT5-MMP (MMP-24) is an essential mediator of peripheral thermal nociception and inflammatory hyperalgesia. We report that MT5-MMP is expressed by CGRP-containing peptidergic nociceptors in dorsal root ganglia and that Mmp24-deficient mice display enhanced sensitivity to noxious thermal stimuli under basal conditions. Consistently, mutant peptidergic sensory neurons hyperinnervate the skin, a phenotype that correlates with changes in the regulated cleavage of the cell-cell adhesion molecule N-cadherin. In contrast to basal nociception, Mmp24-/- mice do not develop thermal hyperalgesia during inflammation, a phenotype that appears associated with alterations in N-cadherin-mediated cell-cell interactions between mast cells and sensory fibers. Collectively, our findings demonstrate an essential role of MT5-MMP in the development of dermal neuro-immune synapses and suggest that this metalloproteinase may be a target for pain control.
Identifiersdoi: 10.1073/pnas.0908507106
issn: 0027-8424
e-issn: 1091-6490
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