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Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats.
Eur J Pain. 2010 Oct; 14(9):911-7.EJ

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 9-40 days after surgery, respectively). At 12 days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10 pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10 nmol, 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 10 nmol). 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 (100 nM) 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.

Authors+Show Affiliations

Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20350830

Citation

Werner, Maria Fernanda P., et al. "Contribution of Peripheral Endothelin ETA and ETB Receptors in Neuropathic Pain Induced By Spinal Nerve Ligation in Rats." European Journal of Pain (London, England), vol. 14, no. 9, 2010, pp. 911-7.
Werner MF, Trevisani M, Campi B, et al. Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats. Eur J Pain. 2010;14(9):911-7.
Werner, M. F., Trevisani, M., Campi, B., André, E., Geppetti, P., & Rae, G. A. (2010). Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats. European Journal of Pain (London, England), 14(9), 911-7. https://doi.org/10.1016/j.ejpain.2010.03.001
Werner MF, et al. Contribution of Peripheral Endothelin ETA and ETB Receptors in Neuropathic Pain Induced By Spinal Nerve Ligation in Rats. Eur J Pain. 2010;14(9):911-7. PubMed PMID: 20350830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats. AU - Werner,Maria Fernanda P, AU - Trevisani,Marcello, AU - Campi,Barbara, AU - André,Eunice, AU - Geppetti,Pierangelo, AU - Rae,Giles A, Y1 - 2010/03/28/ PY - 2009/09/17/received PY - 2010/02/10/revised PY - 2010/03/02/accepted PY - 2010/3/31/entrez PY - 2010/3/31/pubmed PY - 2011/6/21/medline SP - 911 EP - 7 JF - European journal of pain (London, England) JO - Eur J Pain VL - 14 IS - 9 N2 - 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 9-40 days after surgery, respectively). At 12 days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10 pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10 nmol, 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 10 nmol). 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 (100 nM) 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. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/20350830/Contribution_of_peripheral_endothelin_ETA_and_ETB_receptors_in_neuropathic_pain_induced_by_spinal_nerve_ligation_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(10)00047-9 DB - PRIME DP - Unbound Medicine ER -