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Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia.
Eur J Pain. 2010 Feb; 14(2):120.e1-9.EJ

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 approximately 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.

Authors+Show Affiliations

Instituto Venezolano de Investigaciones Cientificas (IVIC), Apartado 20632, Caracas 1020A, Venezuela.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19443247

Citation

Sanoja, Raul, et al. "Role of RVM Neurons in Capsaicin-evoked Visceral Nociception and Referred Hyperalgesia." European Journal of Pain (London, England), vol. 14, no. 2, 2010, pp. 120.e1-9.
Sanoja R, Tortorici V, Fernandez C, et al. Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. Eur J Pain. 2010;14(2):120.e1-9.
Sanoja, R., Tortorici, V., Fernandez, C., Price, T. J., & Cervero, F. (2010). Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. European Journal of Pain (London, England), 14(2), e1-9. https://doi.org/10.1016/j.ejpain.2009.04.006
Sanoja R, et al. Role of RVM Neurons in Capsaicin-evoked Visceral Nociception and Referred Hyperalgesia. Eur J Pain. 2010;14(2):120.e1-9. PubMed PMID: 19443247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. AU - Sanoja,Raul, AU - Tortorici,Victor, AU - Fernandez,Carlos, AU - Price,Theodore J, AU - Cervero,Fernando, Y1 - 2009/05/13/ PY - 2008/12/10/received PY - 2009/04/07/revised PY - 2009/04/07/accepted PY - 2009/5/16/entrez PY - 2009/5/16/pubmed PY - 2010/4/9/medline SP - 120.e1 EP - 9 JF - European journal of pain (London, England) JO - Eur J Pain VL - 14 IS - 2 N2 - 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 approximately 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. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/19443247/Role_of_RVM_neurons_in_capsaicin_evoked_visceral_nociception_and_referred_hyperalgesia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(09)00082-2 DB - PRIME DP - Unbound Medicine ER -