Analgesia of naloxone and morphine in wild-type and NY1DD sickle cell mice using BMAP cDNA microarrays

Sickle cell disease is the most common genetic disorder in African-Americans. The opioid analgesic, morphine, has long been the treatment for the severe pain associated with this disease. Here we reveal that the opioid antagonist, naloxone, possesses potent analgesic activity in two strains of sickle cell mice (NY1DD and hBERK1) and not in their respective controls (ICR-CD1 and C57BL/6J) when administered by three parenteral routes. In the NY1DD sickle mice, naloxone (i.c.v.) possessed ~300-fold greater potency than morphine (i.c.v.). Other opioid antagonists (naltrexone, norbinaltorphimine, naltrindole) were substantially less effective in producing analgesia. Naloxone and morphine were synergistic in NY1DD mice, suggesting that analgesia was mediated via different receptor systems. Since microarray analysis suggested naloxone-induced down-regulation of the CCR5 chemokine receptor in NY1DD mice but not in control mice, the role of its endogenous ligand, CCL5 (RANTES), was investigated. Keywords: Comparison of drug induced gene expression In total 12 samples were analyzed. We used two strains of mice: Wild-type: C57BL/6J Sickle cell: NY1DD To compare the gene expression patterns of naloxone and morphine, 4 treatments were used: i) Naloxone on sickle cell mice - 3 replicates ii) Morphiine on sickle cell mice - 3 replicates iii) Naloxone on wild-type mice - 3 replicates iv) Morphine on wild-type mice - 3 replicates As we used dual channel cDNA microarrays, the experimental (Cy5) channel was used for the drugs (either morphine or naloxone) and the control (Cy3) was always saline treated.