Cholecystokinin antisense RNA increases the analgesic effect induced by electroacupuncture or low dose morphine

Conversion of low responder rats into high responders

Nai Mei Tang, Hongwei Dong, Xiao Min Wang, Zhao Chun Tsui, Ji Sheng Han

Research output: Contribution to journalArticle

81 Citations (Scopus)

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-CCK(AS) 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.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalPain
Volume71
Issue number1
DOIs
StatePublished - May 1 1997

Fingerprint

Electroacupuncture
Antisense RNA
Cholecystokinin
Sincalide
Morphine
Analgesics
Analgesia
Periaqueductal Gray
Opioid Analgesics
Brain
Gene Expression
Cerebral Ventricles
Injections
Opioid Peptides
Lateral Ventricles
Mesencephalon
Neuropeptides
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Cholecystokinin antisense RNA increases the analgesic effect induced by electroacupuncture or low dose morphine : Conversion of low responder rats into high responders. / Tang, Nai Mei; Dong, Hongwei; Wang, Xiao Min; Tsui, Zhao Chun; Han, Ji Sheng.

In: Pain, Vol. 71, No. 1, 01.05.1997, p. 71-80.

Research output: Contribution to journalArticle

Tang, Nai Mei ; Dong, Hongwei ; Wang, Xiao Min ; Tsui, Zhao Chun ; Han, Ji Sheng. / Cholecystokinin antisense RNA increases the analgesic effect induced by electroacupuncture or low dose morphine : Conversion of low responder rats into high responders. In: Pain. 1997 ; Vol. 71, No. 1. pp. 71-80.
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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-CCK(AS) 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.",
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