We previously demonstrated that a single injection of diluted bee venom (DBV) temporarily alleviates thermal hyperalgesia, but not mechanical allodynia, in neuropathic rats. The present study was designed to determine whether repetitive injection of DBV produces more potent analgesic effects on neuropathy-induced nociception and whether those effects are associated with increased neuronal activity in the locus coeruleus (LC) and with the suppression of spinal NMDA receptor NR1 subunit phosphorylation (pNR1). DBV (.25 mg/kg) was administered subcutaneously twice a day for 2 weeks beginning on day 15 post-chronic constrictive injury surgery. Pain responses were examined and potential changes in LC Fos expression and spinal pNR1 expression were determined. Repetitive DBV administration significantly reduced mechanical allodynia, as well as thermal hyperalgesia. The activity of LC noradrenergic neurons was increased and spinal pNR1 expression was significantly suppressed by repetitive DBV as compared with those of vehicle or single DBV injection. These suppressive effects of repetitive DBV on neuropathic pain and spinal pNR1 were prevented by intrathecal pretreatment of idazoxan, an alpha-2 adrenoceptor antagonist. These results indicate that repetitive DBV produces potent analgesic effects on neuropathic pain and this is associated with the activation of the LC noradrenergic system and with a reduction in spinal pNR1. Perspective: The results of current study demonstrate that repetitive administration of DBV significantly suppresses neuropathic pain. Furthermore, this study provides mechanistic information that repetitive treatment of DBV can produce more potent analgesic effect than single DBV treatment, indicating a potential novel strategy for the management of chronic pain.
Bibliographical noteFunding Information:
Supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0016306 ). This research was also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2005-0049404 ).
Copyright 2012 Elsevier B.V., All rights reserved.
- Bee venom
- NMDA receptor
- locus coeruleus
- neuropathic pain