Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain
A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms....
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2015-06-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6651/7/7/2422 |
| _version_ | 1828154970263781376 |
|---|---|
| author | Dongxing Li Younju Lee Woojin Kim Kyungjin Lee Hyunsu Bae Sun Kwang Kim |
| author_facet | Dongxing Li Younju Lee Woojin Kim Kyungjin Lee Hyunsu Bae Sun Kwang Kim |
| author_sort | Dongxing Li |
| collection | DOAJ |
| description | A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (α2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (α1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via α2-adrenegic receptors, but not via the serotonergic system. |
| first_indexed | 2024-04-11T22:46:39Z |
| format | Article |
| id | doaj.art-e0bc66a2cceb4909ae6a118669528137 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T22:46:39Z |
| publishDate | 2015-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-e0bc66a2cceb4909ae6a1186695281372022-12-22T03:58:44ZengMDPI AGToxins2072-66512015-06-01772422243410.3390/toxins7072422toxins7072422Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic PainDongxing Li0Younju Lee1Woojin Kim2Kyungjin Lee3Hyunsu Bae4Sun Kwang Kim5Department of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, KoreaDepartment of East-West Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, KoreaDepartment of Herbology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdamoon-gu, Seoul 130-701, KoreaA single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (α2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (α1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via α2-adrenegic receptors, but not via the serotonergic system.http://www.mdpi.com/2072-6651/7/7/2422phospholipase A2Bee Venomoxaliplatinneuropathic painnoradrenergic |
| spellingShingle | Dongxing Li Younju Lee Woojin Kim Kyungjin Lee Hyunsu Bae Sun Kwang Kim Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain Toxins phospholipase A2 Bee Venom oxaliplatin neuropathic pain noradrenergic |
| title | Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain |
| title_full | Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain |
| title_fullStr | Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain |
| title_full_unstemmed | Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain |
| title_short | Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain |
| title_sort | analgesic effects of bee venom derived phospholipase a2 in a mouse model of oxaliplatin induced neuropathic pain |
| topic | phospholipase A2 Bee Venom oxaliplatin neuropathic pain noradrenergic |
| url | http://www.mdpi.com/2072-6651/7/7/2422 |
| work_keys_str_mv | AT dongxingli analgesiceffectsofbeevenomderivedphospholipasea2inamousemodelofoxaliplatininducedneuropathicpain AT younjulee analgesiceffectsofbeevenomderivedphospholipasea2inamousemodelofoxaliplatininducedneuropathicpain AT woojinkim analgesiceffectsofbeevenomderivedphospholipasea2inamousemodelofoxaliplatininducedneuropathicpain AT kyungjinlee analgesiceffectsofbeevenomderivedphospholipasea2inamousemodelofoxaliplatininducedneuropathicpain AT hyunsubae analgesiceffectsofbeevenomderivedphospholipasea2inamousemodelofoxaliplatininducedneuropathicpain AT sunkwangkim analgesiceffectsofbeevenomderivedphospholipasea2inamousemodelofoxaliplatininducedneuropathicpain |