title: Activation of spinal cholecystokinin and neurokinin-1 receptors is associated with the attenuation of intrathecal morphine analgesia following electroacupuncture stimulation in rats.
abstract: We previously demonstrated that electroacupuncture (EA) stimulation both produced antinociception and attenuated intrathecal (i.t.) morphine analgesia, suggesting that EA is capable of inducing two opposing systems, that is, opioid and anti-opioid mechanisms. This study examined the involvement of cholecystokinin (CCK) in the anti-opioid effects following EA in the spinal cord. EA was applied to commonly used acupoints for antinociception, ST-36 located 5-mm lateral to the anterior tubercle of the tibia, and analgesia was assessed by the hind-paw pressure test in male Sprague-Dawley rats. I.t. administration of CCK (0.01 - 10 microg) attenuated i.t. morphine analgesia (10 microg) dose-dependently. The attenuation of morphine analgesia following EA was reversed by i.t. proglumide, a CCK-receptor antagonist (0.01 microg). CCK-like immunoreactivity was increased in lamina I and II in the dorsal horn, and expression of spinal CCK mRNA increased after EA. Moreover, i.t. pretreatment with the neurokinin-1 (NK1)-receptor antagonist L-703,606 (18 microg) reversed both EA- and CCK-induced attenuation of morphine analgesia. These results suggest that CCK-mediated neural systems in the spinal cord may be involved in the attenuation of morphine analgesia following EA and that substance P-induced activation of NK1 receptors may be responsible for the downstream neuronal transmission of the CCK-mediated neuronal system.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-8509, Japan.
authors.forename: Yohji
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Norikazu
authors.initials: N
authors.lastname: Kiguchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tohya
authors.forename: Michio
authors.initials: M
authors.lastname: Kimura
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D015669:Acupuncture Points; D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002766:Cholecystokinin / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015671:Electroacupuncture; D015870:Gene Expression; D006614:Hindlimb; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D018040:Receptors, Neurokinin-1; D013373:Substance P; D009020:Morphine; D002766:Cholecystokinin