Cholecystokinin antisense RNA increases the analgesic effect induced by electroacupuncture or low dose morphine: conversion of low responder rats into high responders

Abstract

The analgesic effects of the rat in response to electroacupuncture (EA) or low-dose morphine (3 mg/kg) show marked individual variations. In the midbrain periaqueductal gray (PAG) of the rat, the content of the neuropeptide cholecystokinin octapeptide (CCK-8) was found to be significantly higher in the low responder (LR) rats as compared to that in the high responders (HR). Since PAG has been shown to be a strategic site for CCK-8 to exert an anti-opioid action, a high CCK content in PAG may account for the low analgesic responsiveness to EA and morphine. In order to block the expression of the gene encoding preproCCK in the brain, antisense CCK expression vector pSV2-CCKAS was microinjected into the lateral cerebral ventricle of the rat, leading to a decrease of the CCK-mRNA as well as the CCK-8 content in rat brain. This effect started 4 days after the intracerebroventricular (i.c.v.) injection of the antisense expression vector, and lasted no more than 1 week. This procedure was shown to be very effective in converting LR rats into HR for EA analgesia and morphine analgesia, and also delayed the development of tolerance elicited by prolonged EA stimulation or repeated morphine administration. The time course of the augmentation of opioid analgesia (4-6 days after the i.c.v. injection of the expression vector) paralleled the decrease of the brain CCK-8 content. The results argue that blocking the CCK gene expression in the brain may tilt the balance between opioid and anti-opioid peptides in favor of the former, thus strengthening the EA analgesia and morphine analgesia, and delaying the development of opioid tolerance.

Dual effects of acupuncture on gastric motility in conscious rats

“…ST-36 is located on the stomach meridian, whereas BL-21, used as a control, is located on the urinary bladder meridian (7,33). It was previously shown that ST-36 is located 5 mm lateral and lower from the anterior tubercle of the tibia in 200-250 g body wt rats (53). BL-21 is located 5 mm lateral of the spinous process of the 12th thoracic vertebrae (60).…”

Electroacupuncture at ST-36 accelerates colonic motility and transit in freely moving conscious rats

“…Hook-shaped needles were inserted to a depth of 5 mm into the skin and underlying muscles at either ST-36 or BL-21 (Weishu; back) bilaterally. ST-36 is located at 5 mm lateral and lower from the anterior tubercle of the tibia in rats (47). BL-21, used as a sham acupoint, is located at 5 mm lateral of the spinous process of the 12th thoracic vertebrae in rats (53).…”

How Do Acupuncture and Moxibustion Act? – Focusing on the Progress in Japanese Acupuncture Research –

“…The responsiveness to EA was systematically investigated in various mouse strains, and clear differences in EAA were observed (54). In the low-responders, a high content of CCK-8 in the PAG was found; and injection of an antisense CCK expression vector to the lateral cerebral ventricle, which decreases the CCK content in the brain, converted a low-responder to a high-responder (55). A newly found peptide, orphanin FQ (OFQ), has also been proposed as a candidate for modulation of EAA.…”