Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue

Abstract

The effect of inflammation, induced by unilateral intraplantar injection of Freund's adjuvant, on opioid receptors transported in the sciatic nerve and on opioid receptors present in the paw of the rat was studied by means of in vitro receptor autoradiography using [ 125I]β-endorphin (human) as ligand. In the absence of inflammation, human β-endorphin binding sites accumulated proximally and distally to a ligature placed on the sciatic nerve in a time-dependent manner, indicating bidirectional axonal transport. Some human β-endorphin binding was also visible in non-inflamed paw tissue. Inflammation of the paw tissue massively increased human β-endorphin binding on both sides of the sciatic nerve ligature and in the ipsilateral paw tissue. In inflamed paw tissue, β-endorphin binding accumulated in the cutaneous nerve fibers as well as in the immune cells infiltrating the surrounding tissue. In the sciatic nerve and paw tissue, β-endorphin binding was displaced by ( d-Ala 2, N-methyl-Phe 4,Gly-ol 5)enkephalin and ( d-Pen 2, d-Pen 5)enkephalin, selective μ- and δ-opioid receptor agonists, respectively, and by the universal opioid antagonist naloxone, but not by U-50,488H, a k-selective receptor agonist. Taken together, these data provide neuroanatomical evidence for local inflammation-induced enhanced axonal transport of opioid receptors in rat sciatic nerve and accumulation in paw tissue.