title: Transcutaneous iontophoresis of methadone provokes local flushing and thermal hyperalgesia.
abstract: OBJECTIVE
  To investigate whether the introduction of methadone into the skin of the human forearm produces wheals, cutaneous vasodilatation or thermal hyperalgesia and, if so, to determine whether these responses are mediated by opioid receptors.
  
  
  METHODS
  Healthy adults.
  
  
  RESULTS
  In Experiment 1 (N = 11), the increase in local blood flow (monitored with a laser Doppler flowmeter) was greater after the iontophoresis of methadone than saline (mean increase +/- S.D. 12.6 +/- 8.8 versus 2.2 +/- 1.9 times greater than baseline, p < 0.01). Flushing did not spread into surrounding skin and wheals did not form. In Experiment 2, pre-treatment with naloxone (N = 12) prevented increases in blood flow to methadone whereas saline pre-treatment (N = 14) did not. The heat pain threshold was lower at the site of methadone administration than at an untreated site (42.8 +/- 2.3 degrees C versus 44.6 +/- 1.7 degrees C, p < 0.001), and this effect was inhibited by naloxone pre-treatment. However, naloxone pre-treatment also antagonized an inhibitory effect of methadone on the pain generated by a 7-second pulse of 45 degrees C heat. In Experiment 3 (N = 11), the iontophoresis of methadone was repeated after an interval of 1.5 h. Vasodilatation to methadone persisted after the second iontophoresis, and sensitivity to heat was greater at a site of methadone administration than at a site of saline administration or an untreated control site.
  
  
  CONCLUSIONS
  Stimulation of mu-opioid receptors dilated cutaneous blood vessels, and evoked local thermal analgesia and hyperalgesia at different stimulus intensities. However, stimulation of mu-opioid receptors did not produce wheals or flares.
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D005260:Female; D005483:Flushing / Q000139:chemically induced*; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced*; D007478:Iontophoresis; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D009270:Naloxone; D008691:Methadone