Peripheral effects of morphine and expression of µ-opioid receptors in the dorsal root ganglia during neuropathic pain: Nitric oxide signaling


Por: Hervera A., Negrete R., Leánez S., Martín-Campos J.M., Pol O.

Publicada: 1 ene 2011
Resumen:
Background: The local administration of µ-opioid receptor (MOR) agonists attenuates neuropathic pain but the precise mechanism implicated in this effect is not completely elucidated. We investigated if nitric oxide synthesized by neuronal (NOS1) or inducible (NOS2) nitric oxide synthases could modulate the local antiallodynic effects of morphine through the peripheral nitric oxide-cGMP-protein kinase G (PKG)-ATP-sensitive K+(KATP) channels signaling pathway activation and affect the dorsal root ganglia MOR expression during neuropathic pain.Results: In wild type (WT) mice, the subplantar administration of morphine dose-dependently decreased the mechanical and thermal allodynia induced by the chronic constriction of the sciatic nerve (CCI), which effects were significantly diminished after their co-administration with different subanalgesic doses of a selective NOS1 (N-[(4S)-4-amino-5-[(2-aminoethyl)amino]pentyl]-N'-nitroguanidine tris(trifluoroacetate) salt; NANT), NOS2 (L-N(6)-(1-iminoethyl)-lysine; L-NIL), L-guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; ODQ), PKG ((Rp)-8-(para-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate; Rp-8-pCPT-cGMPs) inhibitor or a KATP channel blocker (glibenclamide). The evaluation of the expression of MOR in the dorsal root ganglia from sham-operated and sciatic nerve-injured WT, NOS1 knockout (KO) and NOS2-KO mice at 21 days after surgery demonstrated that, although the basal mRNA and protein levels of MOR were similar between WT and both NOS-KO animals, nerve injury only decreased their expression in WT mice.Conclusions: These results suggest that the peripheral nitric oxide-cGMP-PKG-KATP signaling pathway activation participates in the local antiallodynic effects of morphine after sciatic nerve injury and that nitric oxide, synthesized by NOS1 and NOS2, is implicated in the dorsal root ganglia down-regulation of MOR during neuropathic pain. © 2011 Hervera et al; licensee BioMed Central Ltd.

Filiaciones:
Hervera A.:
 Grup de Neurofarmacologia Molecular, Institut de Recerca de l'Hospital de la Sta Creu i Sant Pau and Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

Negrete R.:
 Grup de Neurofarmacologia Molecular, Institut de Recerca de l'Hospital de la Sta Creu i Sant Pau and Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

Leánez S.:
 Grup de Neurofarmacologia Molecular, Institut de Recerca de l'Hospital de la Sta Creu i Sant Pau and Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

Martín-Campos J.M.:
 Grup de Bioquímica, Institut de Recerca de l'Hospital de la Sta Creu i Sant Pau, Barcelona, Spain

Pol O.:
 Grup de Neurofarmacologia Molecular, Institut de Recerca de l'Hospital de la Sta Creu i Sant Pau and Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain
ISSN: 17448069
Editorial
BIOMED CENTRAL LTD, 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 7 Número:
Páginas:
WOS Id: 000290715400001
ID de PubMed: 21486477
imagen Gold, Green Published, Green

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