100 Hz Electroacupuncture Alleviated Chronic Itch and GRPR Expression Through Activation of Kappa Opioid Receptors in Spinal Dorsal Horn

Abstract

BackgroundClinical studies have shown that electroacupuncture (EA) alleviates chronic itch. Gastrin-releasing peptide receptor (GRPR) and dynorphin (DYN) in the spinal dorsal horn positively or negatively regulate itch, respectively. However, which frequency of EA is effective on relieving chronic itch and reducing the expression of GRPR, whether DYN-A in the spinal cord is involved in the underlying mechanism of the antipruritus effect of EA remains unknown.MethodsThe mixture of acetone and diethyl ether (1:1) [designated as AEW (acetone/diethyl ether and water) treatment] was used to induce the dry skin model of chronic itch. EA was applied to Quchi (LI11) and Hegu (LI4). Western blot was used to detect the expression of GRPR and DYN-A. Immunofluorescence was used to detect the expression of DYN-A.ResultsThe AEW administration induced remarkable spontaneous scratching, enhanced the expression of GRPR, and reduced the expression of DYN-A. Compared with the sham EA, 2 Hz EA, or 15 Hz EA group, 100 Hz EA was the most effective frequency for relieving chronic itch, reducing the expression of GRPR, and increasing the expression of DYN-A in the cervical dorsal horn. Furthermore, intraperitoneal injection of kappa opioid receptors (KORs) antagonist nor-Binaltorphimine dihydrochloride (nor-BNI) significantly reversed the effect of 100 Hz EA on the inhibition of both itching behavior and GRPR expression.ConclusionEA at 100 Hz is the most effective frequency that inhibits chronic itch and GRPR expression through activation of KORs in the spinal dorsal horn, which can effectively guide the clinical treatment and improve the antipruritic effect of acupuncture.

Electroacupuncture reduces chronic itch via cannabinoid CB1 receptors in the ventrolateral periaqueductal gray

“…Previous studies suggest that high-frequency EA (100 Hz) is an effective antipruritic treatment ( Li et al, 2021 ). Therefore, by keeping the EA frequency at 100Hz, we determined what intensity and acupoint loci are most effective.…”

“…The mouse model of chronic dry skin itch was established to observe itch behaviors following previously described procedures ( Akiyama et al, 2012 ). Briefly, a piece of gauze (the area is approximately 15 × 15 mm 2 ) infiltrated with a volume ratio (1:1) of acetone and diethyl ether was applied to the shaved portion of the mouse neck for 15 s and then another piece of gauze infiltrated by distilled water was used for another 30 s, twice a day for 9 consecutive days ( Li et al, 2021 ), which was successful in producing chronic itch. The above acetone/diethyl ether and water treatment is designated as AEW.…”

“…The video was played back, and the number of scratches was counted by two experimenters who were blinded to the experiments groups. A series of one or more scratching movements by the hindlimb directed toward the neck dry skin area was regarded as one scratching bout, which ended when the mouse either bit/licked the toes or placed the hindlimb on the floor ( Li et al, 2021 ).…”

“…The procedures have been described in our previous studies ( Li et al, 2021 ). Briefly, on the 10th day of dry skin induction, mice were anesthetized with sodium pentobarbital (250 mg/kg, i. p.), euthanized, and sacrificed by cervical dislocation.…”

Acupuncture for the Treatment of Itch: Peripheral and Central Mechanisms

“…It may be related to the physical increase of cannabinergic neurotransmitters after the activation of cannabinoid receptor 1 (CB 1 ), which increases the pruritus threshold ( Gingold and Bergasa, 2003 ). In animal models of chronic dry skin pruritus ( Li, 2019 ), the expression of the CB 1 in the midbrain tissue of mice was increased. Electroacupuncture reduced the scratching behavior through significantly downregulating the expression level of the cannabinoid receptor CB 1 .…”