Peripheral effects of morphine and expression of μ-opioid receptors in the dorsal root ganglia during neuropathic pain : nitric oxide signaling
| Autor: | Hervera Abad, Arnau, Negrete, Roger, Leánez, Sergi, Martín-Campos, Jesús M., Pol, Olga, Universitat Autònoma de Barcelona |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Analgesic
Receptors Opioid mu Pharmacology Nitric Oxide Nitric oxide Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Ganglia Spinal medicine lcsh:Pathology Animals Mice Knockout Morphine Naloxone Research Sciatic nerve injury Nerve injury medicine.disease Sciatic Nerve Peptide Fragments Quaternary Ammonium Compounds Anesthesiology and Pain Medicine Allodynia chemistry Opioid Hyperalgesia Anesthesia Neuropathic pain Molecular Medicine Neuralgia medicine.symptom Somatostatin medicine.drug lcsh:RB1-214 Signal Transduction |
| Zdroj: | Molecular Pain Molecular Pain, Vol 7, Iss 1, p 25 (2011) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| Popis: | 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)-(1iminoethyl)-lysine; L-NIL), L-guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; ODQ), PKG ((Rp)-8-(parachlorophenylthio)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. Background Neuropathic pain is a clinical manifestation characterized by the presence of allodynia and hyperalgesia and it is difficult to treat with the most potent analgesic compounds. Recent studies have demonstrated that the peripheral administration of μ-opioid receptor (MOR) agonists elicits antinociception in different models of neuropathic pain [1,2] and that their expression decreases after nerve injury [2,3]. Even so, the precise mechanisms implicated in the peripheral actions of morphine as well as in the expression of MOR during neuropathic pain are not completely elucidated. |
| Databáze: | OpenAIRE |
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