Mobilization of opioid-containing polymorphonuclear cells by hematopoietic growth factors and influence on inflammatory pain

Background: Leukocytes can control inflammatory pain by secretion of opioid peptides, stimulated by cold-water swimming or local injection of corticotropin-releasing factor, and subsequent activation of opioid receptors on peripheral sensory neurons. This study investigated whether mobilization of polymorphonuclear cells (PMN) by granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) enhances immigration of opioid-containing PMN and peripheral opioid analgesia in rats with Freund complete adjuvant-induced hind paw inflammation. Methods: In circulating PMN of rats treated with G-CSF+SCF and sham-treated rats, opioid peptide content was measured by radioimmunoassay. Expression of adhesion molecules (CD62L, CD49d, CD18), in vitro migration in the Boyden chamber, and infiltrating leukocytes were analyzed by flow cytometry. Chemokine messenger RNA transcription was quantified by Light-Cycler polymerase chain reaction. Paw pressure threshold was measured at baseline, after cold-water swimming, and after injection of corticotropin-releasing factor. Results: G-CSF+SCF treatment increased circulating PMN (11-fold, P 0.05). Conclusions: G-CSF+SCF mobilized circulating opioid-containing PMN but had a minor influence on cell migration and peripheral analgesia, probably because of the low expression of chemokines in the inflamed paw and one of the decreased β-endorphin content in PMN.