Use of bulleyaconitine a as an adjuvant for prolonged cutaneous analgesia in the rat

Chi Fei Wang, Peter Gerner, Birgitta Schmidt, Zhen Zhong Xu, Carla Nau, Sho Ya Wang, Ru Rong Ji, Ging Kuo Wang

研究成果: Article

15 引文 (Scopus)

摘要

BACKGROUND:: Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug isolated from Aconitum plants. BLA has several potential targets, including voltage-gated Na channels. We tested whether BLA elicited long-lasting cutaneous analgesia, when co-injected with lidocaine and epinephrine, as a model for prolonged infiltration anesthesia. METHODS:: The local anesthetic properties of BLA were assessed by the patch-clamp technique in HEK293t cells expressing Nav1.7 and Nav1.8 neuronal Na channels, both crucial for nociception. Drug solutions (0.6 mL) were injected subcutaneously via rat shaved dorsal skin. Inhibition of the cutaneous trunci muscle reflex was evaluated by pinpricks. Skin cross-sections were stained with hematoxylin and eosin or with antibodies against PGP9.5. RESULTS:: BLA at 10 μM interacted minimally with resting or inactivated Nav1.7 and Nav1.8 Na channels when infrequently stimulated to +50 mV for 3 ms. However, when stimulated at 2 Hz for 1000 pulses, their peak Na currents were >90% reduced by BLA. This use-dependent inhibition was not significantly reversed after 15-min washing. Complete nociceptive blockade after injection of lidocaine (0.5%)/epinephrine (1:200,000) lasted for approximately 1 h in rats; full recovery occurred after approximately 6 h. Co-injection of 0.125 mM BLA with lidocaine/epinephrine increased the duration of complete nociceptive blockade to 24 h. Full recovery occurred after approximately 6 days. Skin histology including peripheral nerve fibers appeared unaffected by BLA. CONCLUSIONS:: BLA inhibits Nav1.7 and Nav1.8 Na currents in a use-dependent manner. Co-injection of BLA at ≤0.125 mM with lidocaine and epinephrine elicits complete cutaneous analgesia that lasts for up to 24 h without adverse effects.

原文English
頁(從 - 到)1397-1405
頁數9
期刊Anesthesia and analgesia
107
發行號4
DOIs
出版狀態Published - 2008 十月

指紋

Analgesia
Skin
Lidocaine
Epinephrine
Injections
bulleyaconitine A
Aconitum
Nociception
Patch-Clamp Techniques
Local Anesthesia
Hematoxylin
Eosine Yellowish-(YS)
Local Anesthetics
Peripheral Nerves
Nerve Fibers
Reflex
Analgesics
Histology
Anti-Inflammatory Agents
Muscles

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

引用此文

Wang, Chi Fei ; Gerner, Peter ; Schmidt, Birgitta ; Xu, Zhen Zhong ; Nau, Carla ; Wang, Sho Ya ; Ji, Ru Rong ; Wang, Ging Kuo. / Use of bulleyaconitine a as an adjuvant for prolonged cutaneous analgesia in the rat. 於: Anesthesia and analgesia. 2008 ; 卷 107, 編號 4. 頁 1397-1405.
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title = "Use of bulleyaconitine a as an adjuvant for prolonged cutaneous analgesia in the rat",
abstract = "BACKGROUND:: Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug isolated from Aconitum plants. BLA has several potential targets, including voltage-gated Na channels. We tested whether BLA elicited long-lasting cutaneous analgesia, when co-injected with lidocaine and epinephrine, as a model for prolonged infiltration anesthesia. METHODS:: The local anesthetic properties of BLA were assessed by the patch-clamp technique in HEK293t cells expressing Nav1.7 and Nav1.8 neuronal Na channels, both crucial for nociception. Drug solutions (0.6 mL) were injected subcutaneously via rat shaved dorsal skin. Inhibition of the cutaneous trunci muscle reflex was evaluated by pinpricks. Skin cross-sections were stained with hematoxylin and eosin or with antibodies against PGP9.5. RESULTS:: BLA at 10 μM interacted minimally with resting or inactivated Nav1.7 and Nav1.8 Na channels when infrequently stimulated to +50 mV for 3 ms. However, when stimulated at 2 Hz for 1000 pulses, their peak Na currents were >90{\%} reduced by BLA. This use-dependent inhibition was not significantly reversed after 15-min washing. Complete nociceptive blockade after injection of lidocaine (0.5{\%})/epinephrine (1:200,000) lasted for approximately 1 h in rats; full recovery occurred after approximately 6 h. Co-injection of 0.125 mM BLA with lidocaine/epinephrine increased the duration of complete nociceptive blockade to 24 h. Full recovery occurred after approximately 6 days. Skin histology including peripheral nerve fibers appeared unaffected by BLA. CONCLUSIONS:: BLA inhibits Nav1.7 and Nav1.8 Na currents in a use-dependent manner. Co-injection of BLA at ≤0.125 mM with lidocaine and epinephrine elicits complete cutaneous analgesia that lasts for up to 24 h without adverse effects.",
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Wang, CF, Gerner, P, Schmidt, B, Xu, ZZ, Nau, C, Wang, SY, Ji, RR & Wang, GK 2008, 'Use of bulleyaconitine a as an adjuvant for prolonged cutaneous analgesia in the rat', Anesthesia and analgesia, 卷 107, 編號 4, 頁 1397-1405. https://doi.org/10.1213/ane.0b013e318182401b

Use of bulleyaconitine a as an adjuvant for prolonged cutaneous analgesia in the rat. / Wang, Chi Fei; Gerner, Peter; Schmidt, Birgitta; Xu, Zhen Zhong; Nau, Carla; Wang, Sho Ya; Ji, Ru Rong; Wang, Ging Kuo.

於: Anesthesia and analgesia, 卷 107, 編號 4, 10.2008, p. 1397-1405.

研究成果: Article

TY - JOUR

T1 - Use of bulleyaconitine a as an adjuvant for prolonged cutaneous analgesia in the rat

AU - Wang, Chi Fei

AU - Gerner, Peter

AU - Schmidt, Birgitta

AU - Xu, Zhen Zhong

AU - Nau, Carla

AU - Wang, Sho Ya

AU - Ji, Ru Rong

AU - Wang, Ging Kuo

PY - 2008/10

Y1 - 2008/10

N2 - BACKGROUND:: Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug isolated from Aconitum plants. BLA has several potential targets, including voltage-gated Na channels. We tested whether BLA elicited long-lasting cutaneous analgesia, when co-injected with lidocaine and epinephrine, as a model for prolonged infiltration anesthesia. METHODS:: The local anesthetic properties of BLA were assessed by the patch-clamp technique in HEK293t cells expressing Nav1.7 and Nav1.8 neuronal Na channels, both crucial for nociception. Drug solutions (0.6 mL) were injected subcutaneously via rat shaved dorsal skin. Inhibition of the cutaneous trunci muscle reflex was evaluated by pinpricks. Skin cross-sections were stained with hematoxylin and eosin or with antibodies against PGP9.5. RESULTS:: BLA at 10 μM interacted minimally with resting or inactivated Nav1.7 and Nav1.8 Na channels when infrequently stimulated to +50 mV for 3 ms. However, when stimulated at 2 Hz for 1000 pulses, their peak Na currents were >90% reduced by BLA. This use-dependent inhibition was not significantly reversed after 15-min washing. Complete nociceptive blockade after injection of lidocaine (0.5%)/epinephrine (1:200,000) lasted for approximately 1 h in rats; full recovery occurred after approximately 6 h. Co-injection of 0.125 mM BLA with lidocaine/epinephrine increased the duration of complete nociceptive blockade to 24 h. Full recovery occurred after approximately 6 days. Skin histology including peripheral nerve fibers appeared unaffected by BLA. CONCLUSIONS:: BLA inhibits Nav1.7 and Nav1.8 Na currents in a use-dependent manner. Co-injection of BLA at ≤0.125 mM with lidocaine and epinephrine elicits complete cutaneous analgesia that lasts for up to 24 h without adverse effects.

AB - BACKGROUND:: Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug isolated from Aconitum plants. BLA has several potential targets, including voltage-gated Na channels. We tested whether BLA elicited long-lasting cutaneous analgesia, when co-injected with lidocaine and epinephrine, as a model for prolonged infiltration anesthesia. METHODS:: The local anesthetic properties of BLA were assessed by the patch-clamp technique in HEK293t cells expressing Nav1.7 and Nav1.8 neuronal Na channels, both crucial for nociception. Drug solutions (0.6 mL) were injected subcutaneously via rat shaved dorsal skin. Inhibition of the cutaneous trunci muscle reflex was evaluated by pinpricks. Skin cross-sections were stained with hematoxylin and eosin or with antibodies against PGP9.5. RESULTS:: BLA at 10 μM interacted minimally with resting or inactivated Nav1.7 and Nav1.8 Na channels when infrequently stimulated to +50 mV for 3 ms. However, when stimulated at 2 Hz for 1000 pulses, their peak Na currents were >90% reduced by BLA. This use-dependent inhibition was not significantly reversed after 15-min washing. Complete nociceptive blockade after injection of lidocaine (0.5%)/epinephrine (1:200,000) lasted for approximately 1 h in rats; full recovery occurred after approximately 6 h. Co-injection of 0.125 mM BLA with lidocaine/epinephrine increased the duration of complete nociceptive blockade to 24 h. Full recovery occurred after approximately 6 days. Skin histology including peripheral nerve fibers appeared unaffected by BLA. CONCLUSIONS:: BLA inhibits Nav1.7 and Nav1.8 Na currents in a use-dependent manner. Co-injection of BLA at ≤0.125 mM with lidocaine and epinephrine elicits complete cutaneous analgesia that lasts for up to 24 h without adverse effects.

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