科研之友
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摘要
BackgroundWe 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.
MethodsThree 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 (1-20mg/mL/d) of alfentanil and analgesic effects were assessed. 3) Granuloma inducing effects. Dogs received IT alfentanil (20mg/mL/d; N = 5; 22-28 days) or morphine (12mg/mL/d; N = 3; 22-30 days) and spinal cord harvested for histopathology after 22-30 days of infusion.
Results1) Intradermal morphine (10mg/mL) and compound 48-80 (1mg/mL) but not alfentanil at concentrations up to 20mg/mL produced a cutaneous flare. IT alfentanil infusion produced increases in thermal escape latency at concentrations as low as 2mg/mL/day. A significant depression of arousal was noted in the dogs receiving 20mg/mL. Over the 22- to 30-day infusion period, morphine (12mg/mL/day) resulted in granulomas in all three animals examined whereas IT alfentanil at 20mg/mL/day failed to initiate a granuloma in any animal.
ConclusionsThese results support the hypothesis linking MC degranulation and IT granulomas.
- 出版日期2013-9
