Illuminating Sources of Opioid Peptide Production and Degree of Endogenous Pain Inhibition. Rittner et al. (page 500)

Tissue injuries trigger recruitment of granulocytes and monocytes, which help to limit the extent of tissue destruction and simultaneously induce endogenous analgesia. To characterize and quantify subpopulations of opioid peptide–expressing immune cells at different stages of paw inflammation, Rittner et al.  used Freund complete adjuvant–induced hind paw inflammation in male Wistar rats and then harvested tissue samples at 2, 6, and 96 h after injection of Freund complete adjuvant. The harvested cells were characterized by flow cytometry using a monoclonal pan-opioid antibody (3E7) and antibodies against cell surface antigens and by immunohistochemistry using a polyclonal antibody to β-endorphin. After magnetic cell sorting, the researchers used radioimmunoassay to quantify β-endorphin content.

During the early stages of inflammation (2 and 6 h after Freund complete adjuvant inoculation), 66% of opioid peptide–producing (3E7+) leukocytes were HIS48+granulocytes. At 96 h after inoculation, the majority of 3E7+immune cells were ED1+monocytes and macrophages (73%). The total number of 3E7+cells increased 5.6-fold in the 4 days after Freund complete adjuvant inoculation. During the same time period, the β-endorphin content multiplied 3.9-fold. Parallel experiments using cold water swim stress showed a 160% increase in analgesia. Understanding which distinct leukocyte lineages contribute to the expression of opioid peptides at different stages of inflammation may be important for understanding pain in patients with pain in immunosuppressive diseases, such as cancer, diabetes, or acquired immunodeficiency syndrome. It might also aid in the development of novel pain management strategies.