Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia

Raul Sanoja, Victor Tortorici, Carlos Fernandez Pena Acuna, Theodore J. Price, Fernando Cervero

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 ∼ 20 min 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.

Original languageEnglish (US)
Pages (from-to)120.e1-120.e9
JournalEuropean Journal of Pain
Volume14
Issue number2
DOIs
StatePublished - Jan 1 2010

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Nociception
Capsaicin
Hyperalgesia
Neurons
Hot Temperature
Hypersensitivity
Visceral Pain
Peripheral Nerve Injuries
Acute Pain
Microinjections
N-Methylaspartate
Inflammation
Inhibition (Psychology)

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. / Sanoja, Raul; Tortorici, Victor; Fernandez Pena Acuna, Carlos; Price, Theodore J.; Cervero, Fernando.

In: European Journal of Pain, Vol. 14, No. 2, 01.01.2010, p. 120.e1-120.e9.

Research output: Contribution to journalArticle

Sanoja, Raul ; Tortorici, Victor ; Fernandez Pena Acuna, Carlos ; Price, Theodore J. ; Cervero, Fernando. / Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. In: European Journal of Pain. 2010 ; Vol. 14, No. 2. pp. 120.e1-120.e9.
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