Opioid peptide release evoked by noxious stimulation of the hind instep of rats

Previous studies showed that opioids and opioid peptides modulate vascular reactions such as plasma extravasation and vasodilatation through inhibition of substance P release from peripheral nerve endings of primary afferent fibers, and suggested the existence of endogenous opioid peptide activity related to regulation of inflammatory responses. Here we examined the effect of heat stimulation and antidromic stimulation of primary afferent fibers on the release of immunoreactive opioid peptides into the perfusate of the subcutaneous space in the rat instep. Antidromic stimulation of sectioned sciatic and saphenous nerves did not have any significant effect on the release of Met-enkephalin (Met-EK), while immersion of the hind paw in hot water (47 degrees C) for 30 min caused an increase in Met-EK release into the perfusate. High-pressure liquid chromatography of the perfusate revealed that noxious heat stimulation induced increase in release of Leu-enkephalin (Leu-EK) as well as Met-EK, although the maximal concentration of Leu-EK was less than 16% of that of Met-EK. No beta-endorphin was detected in the perfusate before, during or after heating. We conclude that noxious heat stimulation mainly leads to increase in Met-EK, and that this peptide originates mainly, from peripheral cells containing opioid peptides such as immune cells and/or Merkel cells, not from primary afferent fibers.