title: Effect of transdermal opioids in experimentally induced superficial, deep and hyperalgesic pain.
abstract: OBJECTIVE
  Chronic pain and hyperalgesia can be difficult to treat with classical opioids acting predominately at the µ-opioid receptor. Buprenorphine and its active metabolite are believed to act through µ-, κ- and δ-receptors and may therefore possess different analgesic and anti-hyperalgesic effects compared with pure µ-receptor agonists, for example, fentanyl. Here, we have compared the analgesic and anti-hyperalgesic effects of buprenorphine and fentanyl.
  
  
  METHODS
  Twenty-two healthy volunteers were randomized to treatment with transdermal buprenorphine (20 µg·h(-1), 144 h), fentanyl (25 µg·h(-1), 72 h) or placebo patches in a double-blind, cross-over experimental pain study. The experimental pain tests (phasic pain, sensitization) involved pressure at the tibial bone, cutaneous electrical and thermal stimulation, intramuscular nerve growth factor, UVB light burn injury model and intradermal capsaicin-induced hyperalgesia. Pain testing was carried out at baseline, 24, 48, 72 and 144 h after application of the drugs.
  
  
  RESULTS
  Compared with placebo, buprenorphine, but not fentanyl, significantly attenuated pressure at the tibial bone as well as pressure pain in the primary hyperalgesic area induced by UVB light The two drugs were equipotent and better than placebo against cutaneous thermal pain stimulation), but failed to show significant analgesic effect to cutaneous electrical stimulation, nerve growth factor-induced muscle soreness and to capsaicin-induced hyperalgesia.
  
  
  CONCLUSIONS
  Buprenorphine, but not fentanyl, showed analgesic effects against experimentally induced, bone-associated pain and primary hyperalgesia compared with placebo. These tissue- and modality-differentiated properties may reflect the variable effects of opioid drugs observed in individual patients.
authors.affiliation: Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Andresen
authors.forename: C
authors.initials: C
authors.lastname: Staahl
authors.forename: A
authors.initials: A
authors.lastname: Oksche
authors.forename: H
authors.initials: H
authors.lastname: Mansikka
authors.forename: L
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: A M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000279:Administration, Cutaneous; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D002047:Buprenorphine / Q000008:administration & dosage* / Q000009:adverse effects; D002211:Capsaicin / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation / Q000379:methods; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D002047:Buprenorphine; D020932:Nerve Growth Factor; D002211:Capsaicin; D005283:Fentanyl