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Implications of Ca(2+)-activated Cl(-) channels in the delta-opioid receptor-mediated antinociception in the mouse
M Yamazaki1, H Mizoguchi, M Ohsawa
1Department of Anesthesiology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194, Toyama, Japan. myama@ms.toyama-mpu.ac.jp
Abstract:
The present study was designed to investigate the role of Ca(2+)-activated Cl(-) channels in the spinal opioid receptor-mediated antinociception using the mouse tail-flick assay. The antinociception induced by intrathecal (i.t.) administration of a selective delta-opioid receptor agonist [D-Ala(2)]deltorphin II (10 microgram, i.t.) was significantly attenuated by i.t.-pretreatment with selective Ca(2+)-activated Cl(-) channel blockers, IAA-94, flufenamic acid and niflumic acid. By contrast, IAA-94 had no effect on the antinociception induced by i.t.-treated with either the selective mu-opioid receptor agonist [D-Ala(2),N-MePhe(4), Gly-ol(5)]enkephalin or the kappa-opioid receptor agonist U-50,488H. The present results provide evidence for the first time that the Ca(2+)-activated Cl(-) channel is, at least in part, implicated in the delta-, but not the mu- and kappa-opioid receptor-mediated antinociception in the mouse spinal cord.
Insights
Calcium-activated chloride channels are involved in spinal delta-opioid receptor-mediated pain relief. These channels do not affect pain relief mediated by mu- and kappa-opioid receptors in mice.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioid receptors are key targets for pain management.
- The precise mechanisms of spinal opioid-mediated analgesia are not fully understood.
- Calcium-activated chloride channels (Ca(2+)-activated Cl(-) channels) are implicated in neuronal excitability.
Purpose of the Study:
- To investigate the role of Ca(2+)-activated Cl(-) channels in spinal opioid receptor-mediated antinociception.
- To determine if Ca(2+)-activated Cl(-) channels are involved in delta-, mu-, and kappa-opioid receptor pathways.
Main Methods:
- Utilized the mouse tail-flick assay to measure antinociception.
- Administered selective opioid receptor agonists intrathecally (i.t.).
- Pretreated mice with selective Ca(2+)-activated Cl(-) channel blockers (IAA-94, flufenamic acid, niflumic acid).
Main Results:
- Intrathecal administration of a delta-opioid receptor agonist induced antinociception.
- Pretreatment with Ca(2+)-activated Cl(-) channel blockers significantly attenuated delta-opioid receptor-mediated antinociception.
- The blocker IAA-94 did not affect antinociception mediated by mu- or kappa-opioid receptor agonists.
Conclusions:
- Ca(2+)-activated Cl(-) channels play a role in spinal delta-opioid receptor-mediated antinociception.
- This involvement appears specific to the delta-opioid receptor pathway.
- Ca(2+)-activated Cl(-) channels are not implicated in mu- and kappa-opioid receptor-mediated antinociception in the mouse spinal cord.
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