Related Experiment Videos
Inhibiting a spinal dynorphin A component enhances intrathecal morphine antinociception in mice
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Abstract:
Morphine given intracerebroventricularly releases spinal dynorphin A (Dyn) in mice. The present study was undertaken to determine whether morphine given intrathecally (IT) released Dyn. We demonstrated that the antinociceptive action of morphine was enhanced by procedures that are known to attenuate Dyn action. First, coadministration of the opiate antagonists, naloxone (5 fg), norbinaltorphimine (5 fg) or beta-funaltrexamine (0.25 ng) with IT morphine (0.15 microgram, 5 min) increased antinociceptive percentage maximum possible effect (%MPE) from 30% to 65%. Second, dynorphin antiserum (5 micrograms, 1 h, IT), which neutralizes Dyn action, enhanced morphine (0.2 microgram, 5 min, IT) action; MPE of 27% was increased to 60%. Third, production of desensitization to the antagonistic action of Dyn, IT, by pretreatment with morphine [10 mg/kg, 3 h, subcutaneously (SC)], or 2 micrograms, 3 h, IT) or Dyn (1 ng, 1 h, IT) increased the 30% MPE of IT morphine to 60%. Naloxone [1 ng/kg, intraperitoneally (IP)] enhanced IT morphine at a peak time of 20 min. Nalmefene [1 to 100 ng/kg, per os (PO)] enhanced IT morphine action. In conclusion, the present study showed that IT morphine putatively released spinal Dyn.
Insights
Intrathecal morphine administration in mice releases spinal dynorphin A (Dyn), enhancing its own antinociceptive effects. This study confirms that spinal Dyn release mediates morphine
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Morphine administered intracerebroventricularly is known to release spinal dynorphin A (Dyn).
- Dynorphin A plays a role in pain modulation and opioid effects.
Purpose of the Study:
- To investigate whether intrathecal (IT) morphine administration releases spinal Dyn.
- To determine if spinal Dyn release contributes to the antinociceptive action of IT morphine.
Main Methods:
- Administered IT morphine to mice and assessed antinociception.
- Used opiate antagonists (naloxone, norbinaltorphimine, beta-funaltrexamine) to block Dyn action.
- Utilized dynorphin antiserum to neutralize Dyn.
- Induced desensitization to Dyn's antagonistic effects via morphine or Dyn pretreatment.
- Measured antinociceptive percentage maximum possible effect (%MPE).
Main Results:
- Coadministration of opiate antagonists with IT morphine significantly enhanced antinociception (%MPE from 30% to 65%).
- Dynorphin antiserum administration potentiated the antinociceptive effect of IT morphine (%MPE from 27% to 60%).
- Desensitization to Dyn's action increased the antinociceptive effect of IT morphine (%MPE from 30% to 60%).
- Naloxone and Nalmefene also enhanced IT morphine's antinociceptive action.
Conclusions:
- Intrathecal morphine administration putatively releases spinal dynorphin A.
- Spinal dynorphin A release is implicated in the antinociceptive effects of intrathecal morphine.