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Abstract
Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg), but not α1-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor.
Highlights
Paclitaxel is an important chemotherapeutic agent from the bark of Taxus brevifolia [1], which is widely used to treat various tumors [2,3,4]
In order to see the time-elapsed change of paclitaxel-induced mechanical hyperalgesia, In order to see the time‐elapsed change of paclitaxel‐induced mechanical hyperalgesia, we weevaluated evaluated withdrawal responses hind paws mechanical stimulation using a von
Our results showed that 0.5 mg/kg of melittin was more powerful than 1 mg/kg of Bee venom acupuncture (BVA) or 0.12 mg/kg of phospholipase A2 (PLA2)
Summary
Paclitaxel is an important chemotherapeutic agent from the bark of Taxus brevifolia [1], which is widely used to treat various tumors [2,3,4]. Despite its role against the tumors, its usage is often limited, due to the painful peripheral neuropathy occurring after its administration [5]. Symptoms commonly reported are sensory neuropathies, which are paresthesia, loss of tendon reflexes, numbness and pain in the upper and lower extremities. Toxins 2017, 9, 351; doi:10.3390/toxins9110351 www.mdpi.com/journal/toxins patients’ quality of life (QoL), there is still no optimal treatment method or drug to alleviate these neuropathies [5,6]. To explore novel treatments is needed.method or drug to alleviate decrease patients’. Qualityan ofeffort life (QoL), there is still no optimal treatment.
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