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Mechanisms of sensitization of the response of single dorsal root ganglion cells from adult rat to noxious heat
Author(s) -
Galoyan Samuel M.,
Petruska Jeffrey C.,
Mendell Lorne M.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02775.x
Subject(s) - dorsal root ganglion , nerve growth factor , trpv1 , chemistry , capsaicin , tachyphylaxis , tropomyosin receptor kinase a , microbiology and biotechnology , neuroscience , endocrinology , sensory system , biophysics , biology , receptor , transient receptor potential channel , biochemistry
We investigated the regulation by nerve growth factor of the response of sensory neurons to noxious heat (>43 °C). In dissociated dorsal root ganglion neurons (<30 µm) from adult rat we demonstrated, using perforated patch clamp recording, that the inward current elicited in response to noxious heating is enhanced by nerve growth factor and reduced by capsazepine. The tachyphylaxis observed in response to the second of two heat pulses was reversed in most cells when nerve growth factor was introduced into the medium during the 5 min between the two heat stimuli, similar to findings using capsaicin [X. Shu & L.M. Mendell (1999) Neurosci. Lett. 274 , 159–162]. The threshold temperature did not change systematically after nerve growth factor. Using antibodies to TRPV1 and trkA in a subset of cells from which we recorded, we found a virtually perfect correlation between expression of TRPV1 and sensitivity to noxious heat. In addition, trkA expression was perfectly correlated with the ability of nerve growth factor to reverse tachyphylaxis. Thus, this physiological test is a reliable measure of trkA expression in cells sensitive to noxious heat. In agreement with studies in heterologous cells expressing trkA and TRPV1, pharmacologically blocking phospholipase C abolished the effect of nerve growth factor on heat‐evoked currents in cells verified to express trkA. We conclude that the response of dorsal root ganglion neurons to noxious heat is conditioned by nerve growth factor in the same way as their response to capsaicin and that these responses require the presence of trkA and TRPV1.

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