ROLE OF L-TYPE CALCIUM CHANNELS IN LEAD ACETATE-INDUCED ANTINOCICEPTIVE EFFECTS ON FORMALIN TEST IN MICE

1999 ◽  
Vol 18 (4) ◽  
pp. 177-185 ◽  
Author(s):  
Mohammad Abdollahi ◽  
Shekoufeh Nikfar ◽  
Maryam Kakouiee
Keyword(s):  
Calcium Channels ◽  
Lead Acetate ◽  
Formalin Test ◽  
Antinociceptive Effects

Acetaminophen Inhibits Spinal Prostaglandin E2Release after Peripheral Noxious Stimulation 

1999 ◽  
Vol 91 (1) ◽  
pp. 231-239 ◽  
Author(s):  
Uta S. Muth-Selbach ◽  
Irmgard Tegeder ◽  
Kay Brune ◽  
Gerd Geisslinger
Keyword(s):  
Spinal Cord ◽  
Urinary Excretion ◽  
Dorsal Horn ◽  
Formalin Test ◽  
Intraperitoneal Administration ◽  
Noxious Stimulation ◽  
Cyclooxygenase Inhibitor ◽  
Nociceptive Processing ◽  
Pge2 Release

Background Prostaglandin play a pivotal role in spinal nociceptive processing. At therapeutic concentrations, acetaminophen is not a cyclooxygenase inhibitor. inhibitor. Thus, it is antinociceptive without having antiinflammatory or gastrointestinal toxic effects. This study evaluated the role of spinal prostaglandin E2 (PGE2) in antinociception produced by intraperitoneally administered acetaminophen. Methods The PGE2 concentrations in the dorsal horn of the spinal cord were measured after formalin was injected into the hind paw of rats. The effect of antinociceptive doses of acetaminophen (100, 200, and 300 mg/kg given intraperitoneally) on PGE2 levels and flinching behavior was monitored Spinal PGE2 and acetaminophen concentrations were obtained by microdialysis using a probe that was implanted transversely through the dorsal horn of the spinal cord at L4. Furthermore, the effects of acetaminophen on urinary prostaglandin excretion were determined. Results Intraperitoneal administration of acetaminophen resulted in a significant decrease in spinal PGE2 release that was associated with a significant reduction in the flinching behavior in the formalin test Acetaminophen was distributed rapidly into the spinal cord with maximum dialysate concentrations 4560 min after intraperitoneal administration. Urinary excretion of prostanoids (PGE2, PGF2alpha, and 6-keto-PGF1alpha) was not significantly altered after acetaminophen administration. Conclusions The data confirm the importance of PGE2 in spinal nociceptive processing. The results suggest that antinociception after acetaminophen administration is mediated, at least in part, by inhibition of spinal PGE2 release. The mechanism, however, remains unknown. The finding that urinary excretion of prostaglandins was not affected might explain why acetaminophen is antinociceptive but does not compromise renal safety.

Halothane Inhibition of Recombinant Cardiac L-type Ca2+ Channels Expressed in HEK-293 Cells

2005 ◽  
Vol 103 (6) ◽  
pp. 1156-1166 ◽  
Author(s):  
Kevin J. Gingrich ◽  
Son Tran ◽  
Igor M. Nikonorov ◽  
Thomas J. Blanck
Keyword(s):  
Charge Transfer ◽  
Calcium Channels ◽  
Dependent Manner ◽  
Current Time ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Dependent Inactivation ◽  
Voltage Dependent

Background Volatile anesthetics depress cardiac contractility, which involves inhibition of cardiac L-type calcium channels. To explore the role of voltage-dependent inactivation, the authors analyzed halothane effects on recombinant cardiac L-type calcium channels (alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1), which differ by the alpha2/delta1 subunit and consequently voltage-dependent inactivation. Methods HEK-293 cells were transiently cotransfected with complementary DNAs encoding alpha1C tagged with green fluorescent protein and beta2a, with and without alpha2/delta1. Halothane effects on macroscopic barium currents were recorded using patch clamp methodology from cells expressing alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1 as identified by fluorescence microscopy. Results Halothane inhibited peak current (I(peak)) and enhanced apparent inactivation (reported by end pulse current amplitude of 300-ms depolarizations [I300]) in a concentration-dependent manner in both channel types. alpha2/delta1 coexpression shifted relations leftward as reported by the 50% inhibitory concentration of I(peak) and I300/I(peak)for alpha1Cbeta2a (1.8 and 14.5 mm, respectively) and alpha1Cbeta2aalpha2/delta1 (0.74 and 1.36 mm, respectively). Halothane reduced transmembrane charge transfer primarily through I(peak) depression and not by enhancement of macroscopic inactivation for both channels. Conclusions The results indicate that phenotypic features arising from alpha2/delta1 coexpression play a key role in halothane inhibition of cardiac L-type calcium channels. These features included marked effects on I(peak) inhibition, which is the principal determinant of charge transfer reductions. I(peak) depression arises primarily from transitions to nonactivatable states at resting membrane potentials. The findings point to the importance of halothane interactions with states present at resting membrane potential and discount the role of inactivation apparent in current time courses in determining transmembrane charge transfer.

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K+ATP pathway

2015 ◽  
Vol 53 (11) ◽  
pp. 1621-1627 ◽  
Author(s):  
Sonja Vuckovic ◽  
Dragana Srebro ◽  
Katarina Savic Vujovic ◽  
Milica Prostran
Keyword(s):  
Magnesium Sulfate ◽  
Inflammatory Pain ◽  
Pain Model ◽  
Mk 801 ◽  
Antinociceptive Effects

scholarly journals Antinociceptive Efficacy of the µ-Opioid/Nociceptin Peptide-Based Hybrid KGNOP1 in Inflammatory Pain without Rewarding Effects in Mice: An Experimental Assessment and Molecular Docking

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3267
Author(s):  
Maria Dumitrascuta ◽  
Marcel Bermudez ◽  
Olga Trovato ◽  
Jolien De Neve ◽  
Steven Ballet ◽  
...  
Keyword(s):  
Mouse Models ◽  
Inflammatory Pain ◽  
Formalin Test ◽  
Subcutaneous Administration ◽  
Thermal Hyperalgesia ◽  
Nop Receptor ◽  
3D Interaction ◽  
Duration Of Action ◽  
Health Crisis ◽  
Antinociceptive Effects

Opioids are the most effective analgesics, with most clinically available opioids being agonists to the µ-opioid receptor (MOR). The MOR is also responsible for their unwanted effects, including reward and opioid misuse leading to the current public health crisis. The imperative need for safer, non-addictive pain therapies drives the search for novel leads and new treatment strategies. In this study, the recently discovered MOR/nociceptin (NOP) receptor peptide hybrid KGNOP1 (H-Dmt-D-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) was evaluated following subcutaneous administration in mouse models of acute (formalin test) and chronic inflammatory pain (Complete Freund’s adjuvant-induced paw hyperalgesia), liabilities of spontaneous locomotion, conditioned place preference, and the withdrawal syndrome. KGNOP1 demonstrated dose-dependent antinociceptive effects in the formalin test, and efficacy in attenuating thermal hyperalgesia with prolonged duration of action. Antinociceptive effects of KGNOP1 were reversed by naltrexone and SB-612111, indicating the involvement of both MOR and NOP receptor agonism. In comparison with morphine, KGNOP1 was more potent and effective in mouse models of inflammatory pain. Unlike morphine, KGNOP1 displayed reduced detrimental liabilities, as no locomotor impairment nor rewarding and withdrawal effects were observed. Docking of KGNOP1 to the MOR and NOP receptors and subsequent 3D interaction pattern analyses provided valuable insights into its binding mode. The mixed MOR/NOP receptor peptide KGNOP1 holds promise in the effort to develop new analgesics for the treatment of various pain states with fewer MOR-mediated side effects, particularly abuse and dependence liabilities.

Critical role of Cav3.2 T-type calcium channels in the peripheral neuropathy induced by bortezomib, a proteasome-inhibiting chemotherapeutic agent, in mice

Toxicology ◽  
2019 ◽  
Vol 413 ◽  
pp. 33-39 ◽  
Author(s):  
Shiori Tomita ◽  
Fumiko Sekiguchi ◽  
Tomoyo Deguchi ◽  
Takaya Miyazaki ◽  
Yuya Ikeda ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Calcium Channels ◽  
Chemotherapeutic Agent ◽  
Critical Role
Sign in / Sign up

Export Citation Format

Share Document