Objectives: The main purpose of this study was to assess the role of l-arginine/SNAP/NO/cGMP/K channel pathway in analgesic effects of α-terpineol in mice.
Methods: Male NMRI mice were pretreated intraperitoneally with NO precursor (l-arginine, 100 mg/kg), NO synthase inhibitor (l-NAME, 30 mg/kg), NO donor (SNAP, 1 mg/kg), guanylyl cyclase inhibitor (methylene blue, 20 mg/kg), PDE inhibitor (sildenafil, 0.5 mg/kg), K channel blocker (glibenclamide, 10 mg/kg) and naloxone (2 mg/kg) 20 min before the administration of α-terpineol. The formalin test was performed 20 min after the administration of α-terpineol, and nociceptive responses of mice were recorded during 30 min.
Key Findings: A significant and dose-dependent antinociception was produced by α-terpineol (40 and 80 mg/kg) in both the phases of formalin test. The antinociceptive effect of α-terpineol was significantly potentiated by l-arginine in the second phase while significantly antagonized by l-NAME in both phases of formalin test. Also, SNAP and sildenafil non-significantly enhanced-while methylene blue significantly diminished-the antinociceptive effect of α-terpineol in both phases of formalin test. Glibenclamide significantly reversed the α-terpineol-induced antinociception, indicating the involvement of K channels in antinociceptive effect of α-terpineol.
Conclusions: These results indicate that the antinociceptive effect of α-terpineol is mediated through l-arginine/SNAP/NO/cGMP/K channel pathway.
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http://dx.doi.org/10.1111/jphp.12864 | DOI Listing |
The mu-opioid receptor (MOR) is a major target for the treatment of pain. However, opioids are prone to side effects which limit their effectiveness as analgesics and can lead to opioid use disorders or, even, lethal overdose. The systemic administration of opioid agonists makes it both very difficult to decipher their underlying circuit mechanisms of action and to limit drug action to specific receptor subpopulations to isolate therapeutic effects from adverse side effects.
View Article and Find Full Text PDFThe endogenous dynorphin/kappa opioid receptor (KOR) system in the brain mediates the dysphoric effects of stress, and KOR antagonists may have therapeutic potential for the treatment of drug addiction, depression, and psychosis. One class of KOR antagonists, the long-acting norBNI-like antagonists, have been suggested to act by causing KOR inactivation through a cJun-kinase mechanism rather than by competitive inhibition. In this study, we screened for other opioid ligands that might produce norBNI-like KOR inactivation and found that nalfurafine (a G-biased KOR agonist) and nalmefene (a KOR partial agonist) also produce long-lasting KOR inactivation.
View Article and Find Full Text PDFToxicol Appl Pharmacol
January 2025
Department of Animal and Biomedical Sciences, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China. Electronic address:
Opioids are potent analgesics in clinical pain management but exert variable analgesia in different pain types. Opioid-induced constipation is a common side effect of opioid therapy, and whether opioids induce different gastrointestinal motility inhibitions in different pain types is unknown. In this study, we evaluated the antinociceptive effects and inhibition of upper gastrointestinal transit and colonic bead expulsion of morphine, DAMGO, and Deltorphin in mouse CFA chronic inflammatory pain, SNI chronic neuropathic pain, and carrageenan chronic inflammatory pain models.
View Article and Find Full Text PDFExp Eye Res
January 2025
Laboratory of Ocular Immunology, Transplantation and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA. Electronic address:
Substance P (SP) expressed by corneal nerves, is an 11-amino acid long neuropeptide from the tachykinin family, encoded by the Tac1 gene, and binds to neurokinin receptors. SP overexpression is associated with various pathological responses in the cornea including vasodilation, pain, inflammation, and angiogenesis in the normally avascular tissue. This study investigates the role of neurokinin-1 receptor (NK-1R) mediated signaling in nociception, nerve regeneration, and neuronal activation following mechanical corneal injury in mice.
View Article and Find Full Text PDFAnn Agric Environ Med
December 2024
Department of Experimental Pharmacology, Institute of Rural Health, Lublin, Poland.
Introduction And Objective: The aim of the study was to investigate the effect of bee venom on the activity of two analgesics: ketoprofen (a non-steroidal anti-inflammatory drug) and tramadol (an opioid drug) in the acute thermal pain model (hot-plate test) in mice.
Material And Methods: Linear regression analysis was used to evaluate the dose-response relationship between logarithms of drug doses and their resultant maximum possible anti-nociceptive effects in the mouse hot-plate test. Doses that increased the anti-nociceptive effect by 20% (ED values) for bee venom, ketoprofen and tramadol, and their combination were calculated from linear equations.
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