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

Authors

  • Tony L. Yaksh PhD,

    Corresponding author
    1. Anesthesiology Research, Department of Anesthesiology, University of California, San Diego, CA, USA
    • Address correspondence to: Tony L. Yaksh, PhD, Anesthesiology Research, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0818, USA. Email: tyaksh@ucsd.edu

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  • Joanne J. Steinauer BS,

    1. Anesthesiology Research, Department of Anesthesiology, University of California, San Diego, CA, USA
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  • Samantha L. Veesart LAT,

    1. Anesthesiology Research, Department of Anesthesiology, University of California, San Diego, CA, USA
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  • Shelle A. Malkmus BS, RVT

    1. Anesthesiology Research, Department of Anesthesiology, University of California, San Diego, CA, USA
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  • Conflicts of Interest: The authors declared no conflicts of interest.
  • Anesthesiology Research, Department of Anesthesiology, University of California, San Diego, CA, USA
  • For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http://www.wiley.com/bw/submit.asp?ref=1094-7159&site=1
  • All studies were conducted in the Department of Anesthesiology, University of California, San Diego.
  • Source(s) of financial support: This project was supported by NIDA-15353 (TLY).
  • Summary statement: Alfentanil does not degranulate cutaneous mast cells and its intrathecal infusion at the highest concentrations employed, unlike morphine, does not produce intrathecal granulomas in 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.

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