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Pain control in inflammation governed by selectins

Abstract

Opioid-containing immune cells migrate preferentially to inflamed sites, where they release β-endorphin which activates peripheral opioid receptors to inhibit pain 1, 2 . Immunocyte recruitment is a multistep, sequential engagement of various adhesion molecules located on immune cells and vascular endothelium. Selectins mediate the initial phase of immunoctye extravasation into inflamed sites 3, 4 . Here we show that anti-selectin treatment abolishes peripheral opioid analgesia elicited either endogenously (by stress) or by corticotropin-releasing factor. This results from a blockade of the infiltration of immunocytes containing β-endorphin and the consequent decrease of the β-endorphin content in the inflamed tissue. These findings indicate that the immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain in injured tissue. Thus, pain is exacerbated by measures inhibiting the immigration of opioid-producing cells or, conversely, analgesia might be conveyed by adhesive interactions that recruit those cells to injured tissue.

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Figure 1: The effect of fucoidin (10 mg/kg) on the entry of immune cells containing β-endorphin into the paw tissue at 6 h after FCA administration.
Figure 2: The effect of fucoidin on peripheral endogenous (a and b) and exogenous (c and d) opioid analgesia.
Figure 3: The effect of fucoidin (10 mg/kg) on β-endorphin content in inflamed paws.

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Acknowledgements

We thank S. R. Goldberg for his continuous support and R. Tauber for critical comments on the manuscript. H.M. was on leave from the Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

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Machelska, H., Cabot, P., Mousa, S. et al. Pain control in inflammation governed by selectins. Nat Med 4, 1425–1428 (1998). https://doi.org/10.1038/4017

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