Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists
Abstract
This project is based on the observation in our laboratories that chemokines (small proteins produced by cells of the immune system released from injured cells during inflammatory processes) decrease the analgesic potency of opioid drugs. The hypothesis being tested was that blocking the activity of the chemokines by administering chemokine receptor antagonists (CRAs) would restore the analgesic potency of opioids. It was found that the combination of 2 CRAs, administered with a submaximal analgesic dose of morphine in the rat incisional pain assay, resulted in maximal analgesia and a 3.3-fold shift in the morphine dose-response curve to the left. The morphine-CRA combination resulted in down-regulation of a broad panel of immune mediators induced by the incision. CRAs also potentiated the analgesic potency of oxycodone and meperidine. In the rat cold-water tail flick test, a submaximal dose of morphine in combination with maraviroc alone, with AMD3100 plus maraviroc, or with four CRAs, produced significant synergistic increases in antinociception. In the mouse formalin pain test, AMD3100 plus morphine produced an additive effect on pain, and 4 CRAs plus morphine had a significant interaction. These results show that CRAs could lead to therapies that are "opioid-sparing", but still able to provide optimal analgesia.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1086026
Entities
People
- Martin W. Adler
- Toby K. Eisenstein