Involvement of the nitric oxide-cyclic GMP-protein kinase G-K+ channel pathway in the antihyperalgesic effects of bovine lactoferrin in a model of neuropathic pain.

Abstract

The possible involvement of the nitric oxide (NO)-cyclic GMP (cGMP)-protein kinase G (PKG) pathway on bovine lactoferrin (BLF)-induced spinal antihyperalgesic activity was elucidated in sciatic nerve injured rats. Intrathecal BLF reduced thermal hyperalgesia in a dose-dependent manner. Pretreatment with NG-L-nitro-arginine methyl ester (L-NAME, non-specific inhibitor of NO synthase), 7-nitroindazole (7-NI, neuronal NO synthase inhibitor), 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, guanylyl-cyclase inhibitor), (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2, 9-dimethyl-1-oxo-9, 12-epoxy-1H-diindolo-[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT-5823, specific PKG inhibitor) or glybenclamide (ATP-sensitive K+ channel blocker), but not NG-D-nitro-arginine methyl ester (D-NAME, an inactive enantiomer of l-NAME), d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH2 (CTOP, selective mu-opioid receptor antagonist) or naloxone (nonselective opioid receptor antagonist) prevented BLF-induced antihyperalgesia. Data suggest that BLF-induced spinal antihyperalgesia could be due to activation of the NO-cGMP-PKG-K+ channel pathway and it is not mediated by mu-opioid receptor in a model of neuropathic pain.

• Authors: Jun Wang, Li-Cai Zhang, You-Wen Lv, Yong Ji, Xue-Jun Yan, Jin-Pei Xue
• Journal: Brain research (Brain Res) Vol. 1209 Pg. 1-7 (May 13 2008) ISSN: 0006-8993 [Print] Netherlands
• PMID: 18406400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Enzyme Inhibitors
• Narcotic Antagonists
• Potassium Channel Blockers
• Potassium Channels
• Receptors, Opioid, mu
• Nitric Oxide
• Cyclic GMP-Dependent Protein Kinases
• Lactoferrin
• Cyclic GMP

Topics

• Analgesics (pharmacology, therapeutic use)
• Animals
• Cattle
• Cyclic GMP (metabolism)
• Cyclic GMP-Dependent Protein Kinases (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Hyperalgesia (drug therapy, metabolism, physiopathology)
• Injections, Spinal
• Lactoferrin (pharmacology, therapeutic use)
• Male
• Narcotic Antagonists (pharmacology)
• Neurons, Afferent (drug effects, metabolism)
• Nitric Oxide (metabolism)
• Peripheral Nervous System Diseases (drug therapy, metabolism, physiopathology)
• Potassium Channel Blockers (pharmacology)
• Potassium Channels (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid, mu (drug effects, metabolism)
• Signal Transduction (drug effects, physiology)