Endothelins (ETs) contribute to the sensory changes seen in animals models of inflammatory, cancer and diabetic neuropathic pain, but little is known about their nociceptive role following peripheral nerve injury. The current study evaluated mechanisms by which ETs can drive changes in nociceptive responses to thermal stimulation of the hind paw of rats induced by unilateral lumbar L5/L6 spinal nerve ligation (SNL) injury. SNL sensitizes rats to acetone-evoked cooling of and radiant heat application (Hargreaves test) to the ipsilateral hind paw (throughout 3-40 and 9-40days after surgery, respectively). At 12days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10nmol, i.pl), but unchanged by the selective ET(B) peptidic antagonist (BQ-788). Cold allodynia evoked by cooling the ipsilateral hind paw with acetone was reduced by i.pl. injection of both antagonists BQ-123 or BQ-788 (3 or 10nmol). In contrast, heat hyperalgesia evaluated by Hargreaves method was reduced only by BQ-123. SNL enhanced the [Ca(+2)](i) increases induced by ET-1 (100nM) in neurons from L5/L6 (injured) and L4 (intact) cultured dorsal root ganglion, but did not change the responses of non-neuronal cells. Furthermore, Western blot analysis revealed that SNL increased ET(A) and ET(B) receptor protein expression in spinal nerves. Thus, SNL induces marked hind paw hypersensitivity to thermal stimulation in part via up-regulation of peripheral sensory nerve pronociceptive ET(A) and ET(B) receptor-operated mechanisms. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Contribution of peripheral endothelin ET(A) and ET(B) receptors in neuropathic pain induced by spinal nerve ligation in rats

TREVISANI, Marcello
Secondo
;
CAMPI, Barbara;GEPPETTI, Pierangelo
Penultimo
;
2010

Abstract

Endothelins (ETs) contribute to the sensory changes seen in animals models of inflammatory, cancer and diabetic neuropathic pain, but little is known about their nociceptive role following peripheral nerve injury. The current study evaluated mechanisms by which ETs can drive changes in nociceptive responses to thermal stimulation of the hind paw of rats induced by unilateral lumbar L5/L6 spinal nerve ligation (SNL) injury. SNL sensitizes rats to acetone-evoked cooling of and radiant heat application (Hargreaves test) to the ipsilateral hind paw (throughout 3-40 and 9-40days after surgery, respectively). At 12days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10nmol, i.pl), but unchanged by the selective ET(B) peptidic antagonist (BQ-788). Cold allodynia evoked by cooling the ipsilateral hind paw with acetone was reduced by i.pl. injection of both antagonists BQ-123 or BQ-788 (3 or 10nmol). In contrast, heat hyperalgesia evaluated by Hargreaves method was reduced only by BQ-123. SNL enhanced the [Ca(+2)](i) increases induced by ET-1 (100nM) in neurons from L5/L6 (injured) and L4 (intact) cultured dorsal root ganglion, but did not change the responses of non-neuronal cells. Furthermore, Western blot analysis revealed that SNL increased ET(A) and ET(B) receptor protein expression in spinal nerves. Thus, SNL induces marked hind paw hypersensitivity to thermal stimulation in part via up-regulation of peripheral sensory nerve pronociceptive ET(A) and ET(B) receptor-operated mechanisms. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.
2010
Werner, M. F.; Trevisani, Marcello; Campi, Barbara; André, E.; Geppetti, Pierangelo; Rae, G. A.
File in questo prodotto:
File Dimensione Formato  
werner2010.pdf

solo gestori archivio

Descrizione: Full text editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 661.33 kB
Formato Adobe PDF
661.33 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1395817
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 23
social impact