The local and systemic actions of duloxetine in allodynia and hyperalgesia using a rat skin incision pain model

Chi Fei Wang, Gabriella Russell, Gary R. Strichartz, Ging Kuo Wang

研究成果: Article

10 引文 (Scopus)

摘要

BACKGROUND: Duloxetine is an antidepressant effective for major depressive disorder and also the alleviation of pain for patients with diabetic peripheral neuropathy, chronic musculoskeletal pain, and fibromyalgia. How duloxetine works in pain relief remains unknown. In this study, we address whether duloxetine could act as an analgesic via systemic and local applications. METHODS: Efficacies of bupivacaine and duloxetine applied subcutaneously at the incision site against acute postoperative pain were compared after rat skin incision. Contralateral and intraperitoneal injections were used to assess systemic efficacy of duloxetine. Local anesthetic actions were assayed through functional block of the rat sciatic nerve. Inhibition by duloxetine of neuronal Na+ channels was characterized in rat GH3 cells. RESULTS: Our studies showed that subcutaneous duloxetine (2 mg) reduced hyperalgesia and allodynia for several days after skin incision, whereas subcutaneous bupivacaine (2 mg) did not. Contralaterally injected duloxetine (10 mg) had minimal effects on postoperative pain. Intraperitoneal duloxetine also reduced both allodynia and hyperalgesia, albeit at higher doses (10-20 mg). Duloxetine (2 mg) inhibited motor and nociceptive functions via sciatic nerve block for approximately 24 hours. It also reduced Na+ currents with 50% inhibitory concentrations of 30.4 ± 1.2 μM and 4.26 ± 0.19 μM (n = 8) for resting and fast-inactivated channels, respectively. Furthermore, duloxetine (10 μM) elicited additional use-dependent block of peak Na+ currents by approximately 70% when stimulated at 5 Hz. CONCLUSIONS: Our results demonstrate that duloxetine can act as a local anesthetic and an analgesic drug via both local and systemic applications. Because duloxetine inhibits neuronal Na+ currents with high potency, it may exert its antihyperalgesic effects through inhibition of the spontaneous nerve impulses that result from peripheral injury, encompassing its actions on multiple central nervous system and peripheral targets.

原文English
頁(從 - 到)532-544
頁數13
期刊Anesthesia and analgesia
121
發行號2
DOIs
出版狀態Published - 2015 八月 25

指紋

Hyperalgesia
Pain
Skin
Bupivacaine
Sciatic Nerve
Postoperative Pain
Local Anesthetics
Duloxetine Hydrochloride
Analgesics
Musculoskeletal Pain
Fibromyalgia
Diabetic Neuropathies
Nerve Block
Major Depressive Disorder
Acute Pain
Peripheral Nervous System Diseases
Intraperitoneal Injections
Chronic Pain
Antidepressive Agents
Action Potentials

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

引用此文

Wang, Chi Fei ; Russell, Gabriella ; Strichartz, Gary R. ; Wang, Ging Kuo. / The local and systemic actions of duloxetine in allodynia and hyperalgesia using a rat skin incision pain model. 於: Anesthesia and analgesia. 2015 ; 卷 121, 編號 2. 頁 532-544.
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abstract = "BACKGROUND: Duloxetine is an antidepressant effective for major depressive disorder and also the alleviation of pain for patients with diabetic peripheral neuropathy, chronic musculoskeletal pain, and fibromyalgia. How duloxetine works in pain relief remains unknown. In this study, we address whether duloxetine could act as an analgesic via systemic and local applications. METHODS: Efficacies of bupivacaine and duloxetine applied subcutaneously at the incision site against acute postoperative pain were compared after rat skin incision. Contralateral and intraperitoneal injections were used to assess systemic efficacy of duloxetine. Local anesthetic actions were assayed through functional block of the rat sciatic nerve. Inhibition by duloxetine of neuronal Na+ channels was characterized in rat GH3 cells. RESULTS: Our studies showed that subcutaneous duloxetine (2 mg) reduced hyperalgesia and allodynia for several days after skin incision, whereas subcutaneous bupivacaine (2 mg) did not. Contralaterally injected duloxetine (10 mg) had minimal effects on postoperative pain. Intraperitoneal duloxetine also reduced both allodynia and hyperalgesia, albeit at higher doses (10-20 mg). Duloxetine (2 mg) inhibited motor and nociceptive functions via sciatic nerve block for approximately 24 hours. It also reduced Na+ currents with 50{\%} inhibitory concentrations of 30.4 ± 1.2 μM and 4.26 ± 0.19 μM (n = 8) for resting and fast-inactivated channels, respectively. Furthermore, duloxetine (10 μM) elicited additional use-dependent block of peak Na+ currents by approximately 70{\%} when stimulated at 5 Hz. CONCLUSIONS: Our results demonstrate that duloxetine can act as a local anesthetic and an analgesic drug via both local and systemic applications. Because duloxetine inhibits neuronal Na+ currents with high potency, it may exert its antihyperalgesic effects through inhibition of the spontaneous nerve impulses that result from peripheral injury, encompassing its actions on multiple central nervous system and peripheral targets.",
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The local and systemic actions of duloxetine in allodynia and hyperalgesia using a rat skin incision pain model. / Wang, Chi Fei; Russell, Gabriella; Strichartz, Gary R.; Wang, Ging Kuo.

於: Anesthesia and analgesia, 卷 121, 編號 2, 25.08.2015, p. 532-544.

研究成果: Article

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T1 - The local and systemic actions of duloxetine in allodynia and hyperalgesia using a rat skin incision pain model

AU - Wang, Chi Fei

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AU - Strichartz, Gary R.

AU - Wang, Ging Kuo

PY - 2015/8/25

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N2 - BACKGROUND: Duloxetine is an antidepressant effective for major depressive disorder and also the alleviation of pain for patients with diabetic peripheral neuropathy, chronic musculoskeletal pain, and fibromyalgia. How duloxetine works in pain relief remains unknown. In this study, we address whether duloxetine could act as an analgesic via systemic and local applications. METHODS: Efficacies of bupivacaine and duloxetine applied subcutaneously at the incision site against acute postoperative pain were compared after rat skin incision. Contralateral and intraperitoneal injections were used to assess systemic efficacy of duloxetine. Local anesthetic actions were assayed through functional block of the rat sciatic nerve. Inhibition by duloxetine of neuronal Na+ channels was characterized in rat GH3 cells. RESULTS: Our studies showed that subcutaneous duloxetine (2 mg) reduced hyperalgesia and allodynia for several days after skin incision, whereas subcutaneous bupivacaine (2 mg) did not. Contralaterally injected duloxetine (10 mg) had minimal effects on postoperative pain. Intraperitoneal duloxetine also reduced both allodynia and hyperalgesia, albeit at higher doses (10-20 mg). Duloxetine (2 mg) inhibited motor and nociceptive functions via sciatic nerve block for approximately 24 hours. It also reduced Na+ currents with 50% inhibitory concentrations of 30.4 ± 1.2 μM and 4.26 ± 0.19 μM (n = 8) for resting and fast-inactivated channels, respectively. Furthermore, duloxetine (10 μM) elicited additional use-dependent block of peak Na+ currents by approximately 70% when stimulated at 5 Hz. CONCLUSIONS: Our results demonstrate that duloxetine can act as a local anesthetic and an analgesic drug via both local and systemic applications. Because duloxetine inhibits neuronal Na+ currents with high potency, it may exert its antihyperalgesic effects through inhibition of the spontaneous nerve impulses that result from peripheral injury, encompassing its actions on multiple central nervous system and peripheral targets.

AB - BACKGROUND: Duloxetine is an antidepressant effective for major depressive disorder and also the alleviation of pain for patients with diabetic peripheral neuropathy, chronic musculoskeletal pain, and fibromyalgia. How duloxetine works in pain relief remains unknown. In this study, we address whether duloxetine could act as an analgesic via systemic and local applications. METHODS: Efficacies of bupivacaine and duloxetine applied subcutaneously at the incision site against acute postoperative pain were compared after rat skin incision. Contralateral and intraperitoneal injections were used to assess systemic efficacy of duloxetine. Local anesthetic actions were assayed through functional block of the rat sciatic nerve. Inhibition by duloxetine of neuronal Na+ channels was characterized in rat GH3 cells. RESULTS: Our studies showed that subcutaneous duloxetine (2 mg) reduced hyperalgesia and allodynia for several days after skin incision, whereas subcutaneous bupivacaine (2 mg) did not. Contralaterally injected duloxetine (10 mg) had minimal effects on postoperative pain. Intraperitoneal duloxetine also reduced both allodynia and hyperalgesia, albeit at higher doses (10-20 mg). Duloxetine (2 mg) inhibited motor and nociceptive functions via sciatic nerve block for approximately 24 hours. It also reduced Na+ currents with 50% inhibitory concentrations of 30.4 ± 1.2 μM and 4.26 ± 0.19 μM (n = 8) for resting and fast-inactivated channels, respectively. Furthermore, duloxetine (10 μM) elicited additional use-dependent block of peak Na+ currents by approximately 70% when stimulated at 5 Hz. CONCLUSIONS: Our results demonstrate that duloxetine can act as a local anesthetic and an analgesic drug via both local and systemic applications. Because duloxetine inhibits neuronal Na+ currents with high potency, it may exert its antihyperalgesic effects through inhibition of the spontaneous nerve impulses that result from peripheral injury, encompassing its actions on multiple central nervous system and peripheral targets.

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