Alfentanil: Correlations Between Absence of Effect Upon Subcutaneous Mast Cells and Absence of Granuloma Formation After Intrathecal Infusion in the Dog

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) C utaneous 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/ m L /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.