On the role of cholecystokinin in the mediation of spinal reflex excitability in intact and axotomized rats.
The effects of intrathecal (i.t.) administration of cholecystokinin (CCK) on the hindlimb flexor withdrawal reflex were compared in decerebrate, spinalized, unanaesthetized rats with intact sciatic nerves or 14-26 days after unilateral transection of the sciatic nerve. The effect of CI-988, a CCK-B receptor antagonist, on the facilitation of the flexor reflex induced by conditioning stimulation (CS) of C-afferents was also examined. Intrathecal CCK induced facilitation of the flexor reflex over the dose range of 10 ng-1 micrograms in rats with intact and sectioned sciatic nerves. However, the facilitation induced by CCK in axotomized rats was significantly reduced compared with nerve intact animals. CI-988 did not block the facilitation of the flexor reflex induced by the CS and the increases in reflex magnitude during the CS train (wind-up) in rats with intact and sectioned sciatic nerves. The present results indicate that the excitatory effect of CCK on the spinal cord is reduced after axotomy, suggesting that nerve section may induce transsynaptic changes in the spinal cord leading to hyposensitivity to CCK. Furthermore, it is suggested that CCK may not play a significant role in the phenomenon of wind-up and central sensitization after repetitive C-fiber input under normal conditions or after axotomy, when expression of CCK and CCK-B receptors are increased in sensory neurons.
Lucas
G A
GA
Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.
Xu
X J
XJ
Wiesenfeld-Hallin
Z
Z
D000818:Animals; D019771:Axotomy; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D009412:Nerve Fibers / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012018:Reflex / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology* / Q000601:surgery
D007211:Indoles; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine; D002766:Cholecystokinin