Abstract | BACKGROUND: RESULTS: We used the Complete Freund's Adjuvant model of inflammatory pain, and examined the effectiveness of the delta agonist, SNC80, to both inhibit Ca2+ channels in primary afferent neurons and to attenuate mechanical allodynia. In naïve beta-arrestin 2 wildtype and knockout mice, SNC80 neither significantly inhibited voltage-dependent Ca2+ currents nor produced antinociception. However, following inflammatory pain, both measures showed a significant and long-lasting enhancement of delta opioid receptor function that persisted for up to 14 days post-injury regardless of genotype. Furthermore, although this pain model did not alter Ca2+ current density, the contribution of N-type Ca2+ channels to the total current appeared to be regulated by the presence of beta-arrestin 2. CONCLUSIONS: Our results indicate that there is an upregulation of delta opioid receptor function following chronic pain. This gain of function is reflected in the increased efficacy of a delta agonist in both behavioral and electrophysiological measures. Overall, this work confirms that delta opioid receptors can be enhanced following tissue injury associated with chronic pain.
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Authors | Amynah Pradhan, Monique Smith, Brenna McGuire, Christopher Evans, Wendy Walwyn |
Journal | Molecular pain
(Mol Pain)
Vol. 9
Pg. 8
(Mar 04 2013)
ISSN: 1744-8069 [Electronic] United States |
PMID | 23497324
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Arrb2 protein, mouse
- Arrestins
- Benzamides
- Calcium Channels
- Piperazines
- Receptors, Opioid, delta
- beta-Arrestin 2
- beta-Arrestins
- 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
- Freund's Adjuvant
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Topics |
- Animals
- Arrestins
(metabolism)
- Benzamides
(pharmacology)
- Calcium Channels
(metabolism)
- Chronic Disease
- Chronic Pain
(metabolism, pathology)
- Freund's Adjuvant
- Ganglia, Spinal
(metabolism, pathology)
- Hyperalgesia
(metabolism, pathology)
- Inflammation
(metabolism, pathology)
- Ion Channel Gating
(drug effects)
- Mice
- Mice, Knockout
- Pain Threshold
(drug effects)
- Piperazines
(pharmacology)
- Receptors, Opioid, delta
(metabolism)
- beta-Arrestin 2
- beta-Arrestins
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