title: Alfentanil: correlations between absence of effect upon subcutaneous mast cells and absence of granuloma formation after intrathecal infusion in the dog.
abstract: BACKGROUND
  We hypothesize that intrathecal (IT) granulomas arising from the IT infusion of several opiates may result from the degranulation of meningeal mast cells (MC). Given functional covariance between cutaneous and meningeal MC, we propose that opioids that do not degranulate cutaneous MC will not produce a granuloma. An opioid meeting this criteria is the phenylpiperadine alfentanil HCl.
  
  
  METHODS
  Three experiments were accomplished in dogs. 1) Cutaneous MC degranulation. Flare areas on the dog abdomen were measured after intradermal alfentanil, morphine, or compound 48-80. 2) Dose ranging of analgesic effects of IT alfentanil infusion. Dogs with lumbar IT catheters received continuous infusion for 24 hours of different concentrations (1-20 mg/mL/d) of alfentanil and analgesic effects were assessed. 3) Granuloma inducing effects. Dogs received IT alfentanil (20 mg/mL/d; N = 5; 22-28 days) or morphine (12 mg/mL/d; N = 3; 22-30 days) and spinal cord harvested for histopathology after 22-30 days of infusion.
  
  
  RESULTS
  1) Intradermal morphine (10 mg/mL) and compound 48-80 (1 mg/mL) but not alfentanil at concentrations up to 20 mg/mL produced a cutaneous flare. IT alfentanil infusion produced increases in thermal escape latency at concentrations as low as 2 mg/mL/day. A significant depression of arousal was noted in the dogs receiving 20 mg/mL. Over the 22- to 30-day infusion period, morphine (12 mg/mL/day) resulted in granulomas in all three animals examined whereas IT alfentanil at 20 mg/mL/day failed to initiate a granuloma in any animal.
  
  
  CONCLUSIONS
  These results support the hypothesis linking MC degranulation and IT granulomas.
authors.affiliation: Anesthesiology Research, Department of Anesthesiology, University of California, San Diego, CA, USA.
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
authors.forename: Joanne J
authors.initials: JJ
authors.lastname: Steinauer
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Veesart
authors.forename: Shelle A
authors.initials: SA
authors.lastname: Malkmus
mesh_terms: D015760:Alfentanil / Q000008:administration & dosage*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006099:Granuloma / Q000139:chemically induced*; D007278:Injections, Spinal; D008407:Mast Cells / Q000502:physiology*; D009020:Morphine / Q000008:administration & dosage; D012867:Skin / Q000473:pathology*
chemical_list: D000701:Analgesics, Opioid; D015760:Alfentanil; D009020:Morphine