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. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 236-240 |
| Number of pages | 5 |
| Journal | Regional anesthesia and pain medicine |
| Volume | 36 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2011 May 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Anesthesiology and Pain Medicine
Cite this
}
Prolonged cutaneous analgesia with transdermal application of amitriptyline and capsaicin. / Colvin, Anna Christin; Wang, Chi-Fei; Soens, Mieke A.; Mitani, Aya A.; Strichartz, Gary; Gerner, Peter.
In: Regional anesthesia and pain medicine, Vol. 36, No. 3, 01.05.2011, p. 236-240.Research output: Contribution to journal › Article
TY - JOUR
T1 - Prolonged cutaneous analgesia with transdermal application of amitriptyline and capsaicin
AU - Colvin, Anna Christin
AU - Wang, Chi-Fei
AU - Soens, Mieke A.
AU - Mitani, Aya A.
AU - Strichartz, Gary
AU - Gerner, Peter
PY - 2011/5/1
Y1 - 2011/5/1
N2 - 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. 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.
AB - 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. 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.
UR - http://www.scopus.com/inward/record.url?scp=79955606617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955606617&partnerID=8YFLogxK
U2 - 10.1097/AAP.0b013e31820c2c30
DO - 10.1097/AAP.0b013e31820c2c30
M3 - Article
VL - 36
SP - 236
EP - 240
JO - Regional Anesthesia and Pain Medicine
JF - Regional Anesthesia and Pain Medicine
SN - 1098-7339
IS - 3
ER -