Intrathecal administration of Resolvin D1 and E1 decreases hyperalgesia in mice with bone cancer pain: Involvement of endocannabinoid signaling.
Prostaglandins Other Lipid Mediat
; 151: 106479, 2020 12.
Article
in En
| MEDLINE
| ID: mdl-32745525
ABSTRACT
Pain produced by bone cancer is often severe and difficult to treat. Here we examined effects of Resolvin D1 (RvD1) or E1 (RvE1), antinociceptive products of ω-3 polyunsaturated fatty acids, on cancer-induced mechanical allodynia and heat hyperalgesia. Experiments were performed using a mouse model of bone cancer produced by implantation of osteolytic ficrosarcoma into and around the calcaneus bone. Mechanical allodynia and heat hyperalgesia in the tumor-bearing paw were assessed by measuring withdrawal responses to a von Frey monofilament and to radiant heat applied on the plantar hind paw. RvD1, RvE1, and cannabinoid receptor antagonists were injected intrathecally. Spinal content of endocannabinoids was evaluated using UPLC-MS/MS analysis. RvD1 and RvE1 had similar antinociceptive potencies. ED50s for RvD1 and RvE1 in reducing mechanical allodynia were 0.2 pg (0.53 fmol) and 0.6 pg (1.71 fmol), respectively, and were 0.3 pg (0.8 fmol) and 0.2 pg (0.57 fmol) for reducing heat hyperalgesia. Comparisons of dose-response relationships showed equal efficacy for reducing mechanical allodynia, however, efficacy for reducing heat hyperalgesia was greater for of RvD1. Using UPLC-MS/MS we determined that RvD1, but not RvE1, increased levels of the endocannabinoids Anandamide and 2-Arachidonoylglycerol in the spinal cord. Importantly, Resolvins did not alter acute nociception or motor function in naïve mice. Our data indicate, that RvD1 and RvE1 produce potent antiallodynia and antihyperalgesia in a model of bone cancer pain. RvD1 also triggers spinal upregulation of endocannabinoids that produce additional antinociception predominantly through CB2 receptors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone Neoplasms
/
Signal Transduction
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Eicosapentaenoic Acid
/
Docosahexaenoic Acids
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Endocannabinoids
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Cancer Pain
/
Hyperalgesia
Limits:
Animals
Language:
En
Journal:
Prostaglandins Other Lipid Mediat
Journal subject:
ENDOCRINOLOGIA
Year:
2020
Type:
Article
Affiliation country:
United States