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May/June 2011 - Volume 36 - Issue 3 - pp 236-240 less (no) amit skin
doi: 10.1097/AAP.0b013e31820c2c30 problems
Original Articles

Prolonged Cutaneous Analgesia With Transdermal

Application of Amitriptyline and Capsaicin
Colvin, Anna Christin MS; Wang, Chi-Fei MD; Soens, Mieke A.
MD; Mitani, Aya A. MPH; Strichartz, Gary PhD; Gerner, Peter MD

Abstract

Background and Objectives: Capsaicin selectively binds to TRPV1, the vanilloid

subtype 1 of the superfamily of transient receptor potential ion channels, which is
highly expressed in pain-transmitting C fibers. Recent reports have demonstrated
that the coadministration of capsaicin with a local anesthetic (LA) at the rat sciatic
nerve elicits a prolonged nociceptive-selective nerve block, suggesting that activation
of the TRPV1 receptor may allow LAs to enter the nerve through the TRPV1 pore. In
previous studies, we demonstrated that transdermal amitriptyline achieves clinical
analgesic effects and is more potent than lidocaine. Here we examine whether the
combined application of amitriptyline and capsaicin as a transdermal patch will
produce prolonged cutaneous analgesia compared with amitriptyline alone.

Methods: Male Sprague-Dawley rats (weights 250-300 g) were assigned to five

treatment groups (n = 6-8 per group). Transdermal patches containing amitriptyline
with different concentrations of capsaicin were applied for 3 hrs to rats' shaved
backs: 2.5% amitriptyline alone (control group) and in combination with 0.05%,
0.15%, 1%, and 8% capsaicin. Behavioral testing for cutaneous nociception was
conducted before drug application and after patch removal using the cutaneous
trunci muscle reflex. In addition, skin appearance was assessed to determine
irritation by these formulations.

Results: The cutaneous analgesic effect is significantly prolonged when amitriptyline

is applied in combination with 8% capsaicin. Amitriptyline alone provided a
complete block to pinprick for 4.5 hrs, and the time to full recovery was 96 hrs.
Amitriptyline with 8% capsaicin produced a complete block to pinprick for 6 to 9 hrs,
and the time to full recovery was 216 hrs (P = 0.002). Amitriptyline alone causes
toxic effects in skin, whereas the higher the concentration of capsaicin, the less skin
irritation was noted, and the combination of amitriptyline 2.5% with capsaicin 8%
caused no adverse skin reactions.

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Conclusions: This study demonstrates that the combined application of amitriptyline

and capsaicin results in prolonged cutaneous analgesia compared with amitriptyline
alone, suggesting that the activation of the TRPV1 channel by capsaicin facilitates the
passage of amitriptyline into nociceptors. This transdermal patch achieves far longer
cutaneous analgesia than currently available patch applications such as EMLA
cream. The mechanism that underlies the lesser skin irritation noted when
amitriptyline is combined with higher doses of capsaicin compared with
amitriptyline alone is unclear and may be related to a counteraction of amitriptyline-
induced vasoconstriction.

©2011 American Society of Regional Anesthesia and Pain Medicine

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