Mechanisms of Electroacupuncture-Induced Analgesia on Neuropathic Pain in Animal Model

Kim

Biological & Pharmaceutical Bulletin

et al. 2015

Self Cite

Oxaliplatin, a platinum-based chemotherapy drug, often induces acute neuropathic pain, especially cold allodynia, even after a single administration. Subcutaneous injection of diluted bee venom (BV) into acupoints has been used to treat various pain symptoms in traditional oriental medicine. Although we previously demonstrated the suppressive effect of BV injection on oxaliplatin-induced cold allodynia in rats, its neurochemical mechanism remained unclear. This study investigates whether and how the cholinergic system mediates the relieving effect of BV injection on cold allodynia in oxaliplatin-administered rats. The behavioral signs of cold allodynia induced by an oxaliplatin administration (6 mg/kg, intraperitoneally (i.p.)) were evaluated by a tail immersion test in cold water (4°C). BV (0.25 mg/kg, subcutaneously (s.c.)) injection into the Yaoyangguan acupoint, located between the spinous processes of the fourth and fifth lumbar vertebrae, significantly alleviated the cold allodynia. This relieving effect of BV injection on oxaliplatin-induced cold allodynia was blocked by a pretreatment with mecamylamine (a non-selective nicotinic receptor antagonist, 2 mg/kg, i.p.), but not by atropine (a non-selective muscarinic receptor antagonist, 1 mg/kg, i.p.). Further, dihydro-β-erythroidinehydrobromide (DHβE, an α4β2 nicotinic antagonist, 5 mg/kg, i.p.) prevented the antiallodynic effect of BV, whereas methyllycaconitine (an α7 nicotinic antagonist, 6 mg/kg, i.p.) did not. Finally, intrathecal administration of DHβE (10 nM) blocked the BV-induced anti-allodynic effect. These results suggest that nicotinic acetylcholine receptors, especially spinal α4β2 receptors, but not muscarinic receptors, mediate the suppressive effect of BV injection on oxaliplatin-induced acute cold allodynia in rats.Key words oxaliplatin; bee venom; cholinergic; cold allodynia; nicotinic receptor; rat Oxaliplatin is a third-generation platinum-based chemotherapy drug for advanced colorectal cancer.1) Unlike the other platinum compounds (e.g. cisplatin and carboplatin), oxaliplatin does not induce nephrotoxicity and hepatotoxicity, but often induces a very acute painful neuropathy soon after an administration.2) This acute neuropathy is the only major dose-limiting toxicity associated with oxaliplatin use 3) and is characterized by the rapid onset of cold-induced peripheral dysesthesia, paresthesia, or hypoesthesia of the hands, feet, or throat. 4,5) Previous animal studies also have shown that a single administration of oxaliplatin (6 mg/kg, intraperitoneally (i.p.)) reproduces the neurotoxic profile, especially cold allodynia.6,7) However, its mechanism is still unclear and an effective treatment of established neuropathic cold allodynia remains to be found. 8)A subcutaneous injection of diluted bee venom (BV) into acupoints, so called 'bee venom acupuncture,' has been used as a part of traditional oriental medicine to relieve pain and treat various diseases, such as arthritis, rheumatism, cancer, asthma and skin diseases.9-11) It is a kind...

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Nicotinic Acetylcholine Receptors Mediate the Suppressive Effect of an Injection of Diluted Bee Venom into the GV3 Acupoint on Oxaliplatin-Induced Neuropathic Cold Allodynia in Rats

Kim

Biological & Pharmaceutical Bulletin

et al. 2015

Self Cite

“…Acupuncture also has been reported to activate some brain structures such as the periaqueductal gray, nucleus raphe magnus, locus coeruleus, and arcuate nucleus that contribute to descending inhibitory modulation, as well as deactivate multiple limbic areas modulating pain emotion, such as insula and the anterior cingulate cortex. 8,9,20-22,30,42,55,68 …”

Section: Discussionmentioning

confidence: 99%

From Peripheral to Central: The Role of ERK Signaling Pathway in Acupuncture Analgesia

Park

Park²,

Jeon

et al. 2014

The Journal of Pain

Despite accumulating evidence of the clinical effectiveness of acupuncture, its mechanism remains largely unclear. We assume that molecular signaling around the acupuncture needled area is essential for initiating the effect of acupuncture. To determine possible bio-candidates involved in the mechanisms of acupuncture and investigate the role of such bio-candidates in the analgesic effects of acupuncture, we conducted 2 stepwise experiments. First, a genome-wide microarray of the isolated skin layer at the GB34-equivalent acupoint of C57BL/6 mice 1 hour after acupuncture found that a total of 236 genes had changed and that extracellular signal–regulated kinase (ERK) activation was the most prominent bio-candidate. Second, in mouse pain models using formalin and complete Freund adjuvant, we found that acupuncture attenuated the nociceptive behavior and the mechanical allodynia; these effects were blocked when ERK cascade was interrupted by the mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) inhibitor U0126 (.8 μg/μL). Based on these results, we suggest that ERK phosphorylation following acupuncture needling is a biochemical hallmark initiating the effect of acupuncture including analgesia. Perspective This article presents the novel evidence of the local molecular signaling in acupuncture analgesia by demonstrating that ERK activation in the skin layer contributes to the analgesic effect of acupuncture in a mouse pain model. This work improves our understanding of the scientific basis underlying acupuncture analgesia.

“…Based on a systematic review by Chen et al 22 acupuncture points most often used in dealing with diabetic neuropathy are ST36 Zusanli, GB34 Yanglingquan, SP6 Sanyinjiao, KI3 Taixi on the lower extremities, whereas in the upper limb are LI11 Quchi, LI4 Hegu, SJ5 Waiguan, and PC6 Neiguan. Kim et al 23 conducted another systematic review on several experimental studies to see the effect of electro-acupuncture on neuropathic pain. This study showed that stimulation of acupuncture points ST36 Zusanli and SP6 Sanyinjiao could activate μ and δ opioid, GABA-ergic, cholinergic, and 5-HT3 serotonergic receptors in the central nervous system, which not only played a role in various areas of pain, 23 but also in the cellular mechanisms of laser-puncture on wound healing.…”

Section: Discussionmentioning

confidence: 99%

“…Kim et al 23 conducted another systematic review on several experimental studies to see the effect of electro-acupuncture on neuropathic pain. This study showed that stimulation of acupuncture points ST36 Zusanli and SP6 Sanyinjiao could activate μ and δ opioid, GABA-ergic, cholinergic, and 5-HT3 serotonergic receptors in the central nervous system, which not only played a role in various areas of pain, 23 but also in the cellular mechanisms of laser-puncture on wound healing. 4 In addition, the stimulation on ST36 Zusanli and SP6 Sanyinjiao acupuncture points may affect connective tissue through mechanical forces transferred to the extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of combined laser-puncture and conventional wound care to accelerate diabetic foot ulcer healing

et al. 2017

ABSTRAK (-3,25 sampai -0,09) vs -0,36 (-0,81 sampai -1,47) cm 2 , (p=0,000); minggu 3-1 adalah -1,70 (-3,15 sampai -0,01) vs -0,36 (-0,80 sampai -0,28) cm 2 , (p=0,000); dan minggu 4-1 adalah -1,22 (-2,72 sampai 0,00) vs -0,38 (-0,74 sampai -0,57) cm 2 , (p =0,012). Kesimpulan:Terapi laserpunktur efektif mempercepat penyembuhan ulkus kaki diabetik. ABSTRACTBackground: Impaired wound healing is a common complication of diabetes. It has complex pathophysiologic mechanisms and often necessitates amputation. Our study aimed to evaluate the effectiveness of combined laserpuncture and conventional wound care in the treatment of diabetic foot ulcers.