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.