Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain

Abstract

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.

Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression

“…Oxaliplatin (Sigma-Aldrich, St Louis, MO, USA) was delivered at an amount of 6 mg/kg [32, 33], dissolved in 5% glucose (Sigma-Aldrich) solution at a concentration of 2 mg/ml. Oxaliplatin was administered intraperitoneally (i.p.).…”

Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

“…Oxaliplatin (Sigma, St. Louis, MO, USA) was dissolved in a 5% glucose solution at a concentration of 2 mg/mL and was intraperitoneally (i.p.) injected at a dose of 6 mg/kg [ 4 , 45 ]. The same volume of 5% glucose solution was used in the control group.…”

“…The experimenters were blinded to oxaliplatin and any other treatments. Cold and mechanical sensitivities were measured using acetone and von Frey filaments, respectively [ 45 ]. Mice were placed on a wire mesh floor covered with a clear plastic box (12 × 8 × 6 cm), and were habituated for 30 min prior to each testing.…”

Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

“…Bee venom group III sPLA 2 treatment also can strongly alleviate oxaliplatin-induced acute cold and mechanical allodynia in mice by activating the noradrenergic system via α2-adrenegic receptors, but not the serotonergic system [ 84 ].…”