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Role of RVM neurons in capsaicin‐evoked visceral nociception and referred hyperalgesia
Author(s) -
Sanoja Raul,
Tortorici Victor,
Fernandez Carlos,
Price Theodore J.,
Cervero Fernando
Publication year - 2010
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2009.04.006
Subject(s) - rostral ventromedial medulla , nociception , noxious stimulus , hyperalgesia , capsaicin , stimulation , anesthesia , medicine , visceral pain , neuroscience , nociceptor , pharmacology , psychology , receptor
Most forms of visceral pain generate intense referred hyperalgesia but the mechanisms of this enhanced visceral hypersensitivity are not known. The on‐cells of the rostral ventromedial medulla (RVM) play an important role in descending nociceptive facilitation and can be sensitized to somatic mechanical stimulation following peripheral nerve injury or hindpaw inflammation. Here we have tested the hypothesis that visceral noxious stimulation sensitizes RVM ON‐like cells, thus promoting an enhanced descending facilitation that can lead to referred visceral hyperalgesia. Intracolonic capsaicin instillation (ICI) was applied to rats in order to create a hyperalgesic state dependent on noxious visceral stimulation. This instillation produced acute pain‐related behaviors and prolonged referred hyperalgesia that were prevented by the RVM microinjection of AP5, an NMDA selective antagonist. In electrophysiological experiments, ON‐like RVM neurons showed ongoing spontaneous activity following ICI that lasted for and an enhanced responsiveness to von Frey and heat stimulation of the hindpaw and to colorectal distention (CRD) that lasted for at least 50 min post capsaicin administration. Moreover, ON‐like cells acquired a novel response to CRD and responded to heat stimulation in the innocuous range. OFF‐like neurons responded to capsaicin administration with a brief (<5 min) inhibition of activity followed by an enhanced inhibition to noxious stimulation and a novel inhibition to innocuous stimulation (CRD and heat) at early time points (10 min post capsaicin). These results support the hypothesis that noxious visceral stimulation may cause referred hypersensitivity by promoting long‐lasting sensitization of RVM ON‐like cells.