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The role of delta-opioid receptor subtypes in neuropathic pain
J Mika1, R Przewłocki, B Przewłocka
1Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, Poland.
Abstract:
A large body of evidence suggests an important role of delta-opioid receptor agonists in antinociception at the level of the spinal cord. Our study was undertaken to analyse the spinal antinociceptive and antiallodynic effects of delta(1)- and delta(2)-opioid receptor agonists and antagonist after their acute and chronic intrathecal administration in a neuropathic pain model in the rat. In rats with a crushed sciatic nerve, the delta(1)-opioid receptor agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE, 5-25 microg i.t.) and the delta(2)-opioid receptor agonist deltorphin II (1.5-25 microg i.t.) dose dependently antagonized the cold-water allodynia which developed after sciatic nerve injury. These effects of DPDPE were antagonized by 7-benzylidenenaltrexon (BNTX, 1 microg i.t.) while the effects of deltorphin II were antagonized by 5'naltrindole izotiocyanate (5'NTII, 25 microg i.t.). Both agonists had a dose-dependent, statistically significant effect on the tail-flick latency in two tests, with focused light and cold water. Chronic administration of DPDPE (25 microg i.t.) and deltorphin II (15 microg i.t.) resulted in significant prolongation of the reaction time determined on days 2, 4 and 6 post-injury. In conclusion, our results show an antiallodynic and antinociceptive action of DPDPE and deltorphin II at the spinal cord level, which suggests that both delta-opioid receptor subtypes play a similar role in neuropathic pain. This indicates that not only delta(1)- but also delta(2)-opioid receptor agonists can be regarded as potential drugs for the therapy of neuropathic pain.
Insights
Spinal administration of delta-opioid receptor agonists [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) and deltorphin II demonstrated significant antiallodynic and antinociceptive effects in a rat neuropathic pain model.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Delta-opioid receptors are implicated in spinal antinociception.
- Neuropathic pain models are crucial for evaluating pain therapies.
Purpose of the Study:
- To investigate the spinal antinociceptive and antiallodynic effects of delta(1)- and delta(2)-opioid receptor agonists and antagonists.
- To assess these effects after acute and chronic intrathecal administration in a rat neuropathic pain model.
Main Methods:
- Intrathecal administration of delta(1)-opioid receptor agonist DPDPE and delta(2)-opioid receptor agonist deltorphin II in rats with sciatic nerve crush injury.
- Assessment of antiallodynic effects using cold-water allodynia tests and antinociceptive effects using tail-flick latency tests.
- Administration of specific antagonists (BNTX for DPDPE, 5'NTII for deltorphin II) to confirm receptor involvement.
- Evaluation of effects after both acute and chronic drug administration.
Main Results:
- Both DPDPE and deltorphin II dose-dependently antagonized cold-water allodynia and increased tail-flick latency.
- The effects of DPDPE were blocked by BNTX, and deltorphin II's effects were blocked by 5'NTII, confirming receptor specificity.
- Chronic administration of both agonists led to significant and prolonged antiallodynic effects.
Conclusions:
- Delta-opioid receptor agonists DPDPE and deltorphin II exhibit significant antiallodynic and antinociceptive actions at the spinal cord level.
- Both delta(1)- and delta(2)-opioid receptor subtypes play comparable roles in managing neuropathic pain.
- These findings suggest that agonists targeting both delta(1)- and delta(2)-opioid receptors are promising candidates for neuropathic pain therapy.