Conflicts of Interest: The authors declared no conflicts of interest.
Intrathecal Drug Delivery
Alfentanil: Correlations Between Absence of Effect Upon Subcutaneous Mast Cells and Absence of Granuloma Formation After Intrathecal Infusion in the Dog
Article first published online: 21 NOV 2012
© 2012 International Neuromodulation Society
Neuromodulation: Technology at the Neural Interface
Volume 16, Issue 5, pages 459–466, September/October 2013
How to Cite
Yaksh, T. L., Steinauer, J. J., Veesart, S. L. and Malkmus, S. A. (2013), Alfentanil: Correlations Between Absence of Effect Upon Subcutaneous Mast Cells and Absence of Granuloma Formation After Intrathecal Infusion in the Dog. Neuromodulation: Technology at the Neural Interface, 16: 459–466. doi: 10.1111/j.1525-1403.2012.00534.x
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.
- Issue published online: 29 OCT 2013
- Article first published online: 21 NOV 2012
- Manuscript Accepted: 28 SEP 2012
- Manuscript Revised: 20 SEP 2012
- Manuscript Received: 8 AUG 2012
- NIDA-15353 (TLY)
- Intraspinal drug delivery;
- intrathecal admixtures;
- intrathecal drug delivery;
- intrathecal granuloma;
- intrathecal pump;
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.
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.
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.
These results support the hypothesis linking MC degranulation and IT granulomas.