Repetitive Treatment With Diluted Bee Venom Reduces Neuropathic Pain Via Potentiation of Locus Coeruleus Noradrenergic Neuronal Activity and Modulation of Spinal NR1 Phosphorylation in Rats

Kang, Sung-Soo; Roh, Dae Hyun; Yoon, Seo Yeon; Moon, Ji Young; Kim, Hyun Woo; Lee, Hye Jung; Beitz, Alvin J.; Lee, Jang Hern

doi:10.1016/j.jpain.2011.10.012

Cited by 36 publications

(42 citation statements)

References 30 publications

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“…Our previous studies using a rat model of peripheral nerve injury suggested that both of the opioid and noradrenergic systems equally contributed to the anti-allodynic effects of EA [41–43]. On the other hand, BVA has been reported to attenuate neuropathic pain symptoms induced by CCI through activation of α 2 -adrenergic receptors, but not opioid receptors, in the rat spinal cord [22–24]. Similarly, the present results (Figure 4) suggest that the relieving effect of BVA on oxaliplatin-induced cold allodynia involves the noradrenergic, but not opioid, system.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the antinociceptive actions of BVA were reported to be mediated by the noradrenergic system, not by the opioids [19–21]. In peripheral nerve-injured rats, Lee and his colleagues have demonstrated that BVA attenuated mechanical allodynia, heat hyperalgesia, and cold allodynia, mainly through the activation of the central noradrenergic system [22–24]. However, the effect of BVA on oxaliplatin-induced neuropathic pain and its mechanism has not been studied.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Bee Venom Acupuncture on Oxaliplatin-Induced Cold Allodynia in Rats

Lim

Moon

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Oxaliplatin, a chemotherapy drug, often leads to neuropathic cold allodynia after a single administration. Bee venom acupuncture (BVA) has been used in Korea to relieve various pain symptoms and is shown to have a potent antiallodynic effect in nerve-injured rats. We examined whether BVA relieves oxaliplatin-induced cold allodynia and which endogenous analgesic system is implicated. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. BVA (1.0 mg/kg, s.c.) at Yaoyangguan (GV3), Quchi (LI11), or Zusanli (ST36) acupoints significantly reduced cold allodynia with the longest effect being shown in the GV3 group. Conversely, a high dose of BVA (2.5 mg/kg) at GV3 did not show a significant antiallodynic effect. Phentolamine (α-adrenergic antagonist, 2 mg/kg, i.p.) partially blocked the relieving effect of BVA on allodynia, whereas naloxone (opioid antagonist, 2 mg/kg, i.p.) did not. We further confirmed that an intrathecal administration of idazoxan (α 2-adrenergic antagonist, 50 μg) blocked the BVA-induced anti-allodynic effect. These results indicate that BVA alleviates oxaliplatin-induced cold allodynia in rats, at least partly, through activation of the noradrenergic system. Thus, BVA might be a potential therapeutic option in oxaliplatin-induced neuropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Bee Venom Acupuncture on Oxaliplatin-Induced Cold Allodynia in Rats

Lim

Moon

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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“…This mechanism has been implicated in the analgesic effect of acupuncture [Bing et al, 1990 (noxious heat)]. It has recently been reported that repeated injections of diluted bee venom, which lead to the attenuation of both acute pain evoked by a noxious thermal stimulus and chronic (neuropathic) pain evoked by the ligation of the sciatic nerve, activate the LC (Kang et al, 2012). Therefore the analgesic effect of conditioned pain modulation may involve the activation of the pain-inhibiting pathways arising from the LC.…”

Section: Modulation Of Pain By the Lcmentioning

confidence: 99%

Modulation of physiological reflexes by pain: role of the locus coeruleus

Szabadi

2012

Front. Integr. Neurosci.

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The locus coeruleus (LC) is activated by noxious stimuli, and this activation leads to inhibition of perceived pain. As two physiological reflexes, the acoustic startle reflex and the pupillary light reflex, are sensitive to noxious stimuli, this review considers evidence that this sensitivity, at least to some extent, is mediated by the LC. The acoustic startle reflex, contraction of a large body of skeletal muscles in response to a sudden loud acoustic stimulus, can be enhanced by both directly (“sensitization”) and indirectly (“fear conditioning”) applied noxious stimuli. Fear-conditioning involves the association of a noxious (unconditioned) stimulus with a neutral (conditioned) stimulus (e.g., light), leading to the ability of the conditioned stimulus to evoke the “pain response”. The enhancement of the startle response by conditioned fear (“fear-potentiated startle”) involves the activation of the amygdala. The LC may also be involved in both sensitization and fear potentiation: pain signals activate the LC both directly and indirectly via the amygdala, which results in enhanced motoneurone activity, leading to an enhanced muscular response. Pupil diameter is under dual sympathetic/parasympathetic control, the sympathetic (noradrenergic) output dilating, and the parasympathetic (cholinergic) output constricting the pupil. The light reflex (constriction of the pupil in response to a light stimulus) operates via the parasympathetic output. The LC exerts a dual influence on pupillary control: it contributes to the sympathetic outflow and attenuates the parasympathetic output by inhibiting the Edinger-Westphal nucleus, the preganglionic cholinergic nucleus in the light reflex pathway. Noxious stimulation results in pupil dilation (“reflex dilation”), without any change in the light reflex response, consistent with sympathetic activation via the LC. Conditioned fear, on the other hand, results in the attenuation of the light reflex response (“fear-inhibited light reflex”), consistent with the inhibition of the parasympathetic light reflex via the LC. It is suggested that directly applied pain and fear-conditioning may affect different populations of autonomic neurones in the LC, directly applied pain activating sympathetic and fear-conditioning parasympathetic premotor neurones.

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“…PBV possesses a variety of different peptides with melittin as the main component [13] . Repetitive chemical therapy with PBV was able to produce a robust analgesic effect on chronic neuropathic pain [14] . PBV has been reported to have anticancer activities.…”

Section: Observed Efficacymentioning

confidence: 98%