The effects of opioid receptor antagonists on electroacupuncture-produced anti-allodynia/hyperalgesia in rats with paclitaxel-evoked peripheral neuropathy

Abstract

Research supports the effectiveness of acupuncture for conditions such as chronic low back and knee pain. In a five-patient pilot study the modality also improved the symptoms of chemotherapy-induced neuropathic pain. Using an established rat model of paclitaxel-induced peripheral neuropathy, we evaluated the effect of electroacupuncture (EA) on paclitaxel-induced hyperalgesia and allodynia that has not been studied in an animal model. We hypothesize that EA would relieve the paclitaxel-induced mechanical allodynia and hyperalgesia, which was assessed 30 minutes after EA using von Frey filaments. Beginning on day 13, the response frequency to von Frey filaments (4-15 g) was significantly increased in paclitaxel-injected rats compared to those injected with vehicle. EA at 10Hz significantly (p<0.05) decreased response frequency at 4-15 g compared to sham EA; EA at 100Hz only decreased response frequency at 15 g stimulation. Compared to sham EA plus vehicle, EA at 10Hz plus either a μ, δ, or κ opioid receptor antagonist did not significantly decrease mechanical response frequency, indicating that all three antagonists blocked EA inhibition of allodynia and hyperalgesia. Since we previously demonstrated that μ and δ but not κ opioid receptors affect EA anti-hyperalgesia in an inflammatory pain model, these data show that EA inhibits pain through different opioid receptors under varying conditions. Our data indicate that EA at 10Hz inhibits mechanical allodynia/hyperalgesia more potently than does EA at 100Hz. Thus, EA significantly inhibits paclitaxel-induced allodynia/hyperalgesia through spinal opioid receptors, and EA may be a useful complementary treatment for neuropathic pain patients.

A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

“…Indeed the western neurophysiological hypothesis on the mechanism of acupuncture efficacy proposes that needle insertion and stimulation elicits a three-level response: local (at the site of needling) that could encompass the so called “flare reaction”; segmental, that includes all the acupuncture-induced reflex variations in spinal neurotransmission, that is, GABA-ergic one; central, that refers to the overall variation induced by needle stimulation in the activity and feedback response in the brain [35]. Thus, it is possible to link the positive outcome in such studies to the spinal/segmental activation of opioids and/or GABA signalling, in accordance with previous results on animal models [30]. …”

“…Meng and colleagues [30] demonstrated that EA at both low (10 Hz) and high (100 Hz) frequencies was able to improve neuropathic pain in paclitaxel-treated rats. The authors reported that low-frequency EA was more effective than high-frequency EA in relieving neuropathic symptoms and that opioid receptors antagonists (all types) abolished EA effects.…”

Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Four-Arm Randomized Trial on the Effectiveness of Electroacupuncture

“…Different to our protocol, other studies that reported positive effects of acupuncture treatments in CIPN used local points on the extremities like EX-LE 10 (Bafeng), EX-UE 9 (Baxie), and EX-LE 12 (Qiduan) [31, 33–35] or ear acupuncture for neuropathic pain [36]. In particular the local points on the affected limb/region might activate local, segmental, and spinal and central reflexes in accordance with results on animal models [20]. …”

“…The very limited conclusions from these studies resulted either from the small number of treated patients, the uncontrolled study design, or the publications in Chinese journals with merely an abstract in English and therefore not easy to evaluate. Acupuncture in combination with electrostimulation for treating CIPN has rarely been evaluated [18, 19]; however it has been demonstrated to improve neuropathic pain in paclitaxel-treated rats at both low (10 Hz) and high (100 Hz) frequencies [20]. …”

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…Of those, there were only 7 clinical trials [278][279][280][281][282][283][284] and 1 experimental study [285] which was a rat study. The overall conclusion from the systemic review [275] was that acupuncture generally had positive effects on CIPN by reducing the pain score in most studies.…”