The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain

Abstract

Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, 20 μg), or noradrenergic (idazoxan, 10 μg) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.

Antinociceptive and neuroprotective effects of bromelain in chronic constriction injury-induced neuropathic pain in Wistar rats

“…Gabapentin binds with the α2δ subunit of the calcium channel [30]. Findings from this study revealed that gabapentin reverses both thermal and mechanical hypersensitivities, a finding which is in consonant with those of Kim et al [31] in an animal model of neuropathic pain. The antinociceptive effects of gabapentin in a CCI model of neuropathic pain were similar to those of bromelain, although pretreatment with bromelain has a stronger effect on thermal hyperalgesic symptoms and the SFI.…”

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

“…5,6 In addition, combined treatment with EA and gabapentin (an analgesic drug) showed robust and enduring analgesic actions against PTX-induced neuropathy. 7 Furthermore, a phase IIA trial showed that acupuncture attenuated the severity of peripheral neuropathy induced by PTX chemotherapy in breast cancer patients. 8 According to previous basic studies, the anti-nociceptive effect of EA in relieving PTX-induced neuropathic pain was mediated via spinal opioid receptors and the adrenergic pathway, which is similar to the mechanism underlying EA's analgesic actions in other pain models.…”

Bee Venom Acupuncture Attenuates Oxaliplatin-Induced Neuropathic Pain by Modulating Action Potential Threshold in A-Fiber Dorsal Root Ganglia Neurons

“…In our previous studies, BVA significantly attenuated cold and mechanical allodynia induced by oxaliplatin. Moreover, BVA induced an additive effect when simultaneously injected with morphine by increasing the action time in mice injected with a chemotherapeutic agent [8]. Furthermore, three weeks of treatment with BVA in patients with chemotherapy-induced neuropathic pain also resulted in positive effects [21], implying the efficacy of BVA against oxaliplatin-induced neuropathic pain.…”

“…For the past several years, our group has focused on understanding the underlying mechanism of oxaliplatin-induced neuropathic pain and on finding an effective treatment method. The effects of well-known analgesic drugs such as morphine [7], gabapentin [8], and duloxetine [9] have been assessed along with herbal medicines [10][11][12], acupuncture [8,13], and bee venom acupuncture (BVA) [7,[14][15][16]. Bee venom (BV) is composed of peptides, enzymes, amines, and non-peptide components that have a variety of pharmaceutical properties [17].…”