Intracerebroventricular infusion of nerve growth factor induces pain-like response in rats

New strategies have recently been developed where infusion of neurotrophic factors into the brain can rescue different neuronal populations. However, negative side effects have been observed in clinical trials infusing nerve growth factor (NGF) into the lateral ventricle in man, namely pain. Little is known about pain behavior in animals after intracerebroventricular (i.c. v.) neurotrophic injections. Thus, we have examined the effects of i.c.v. i nfusion of NGF for 2 weeks on the behavioral response of rats to mechanical , cold and heat stimulation. Seven micrograms/day of NGF elicited a signifi cant decrease in vocalization threshold to mechanical stimulation and a sig nificantly increased response to cold and heat stimuli as compared with con trol. The concentration of NGF in cerebrospinal fluid (CSF) was significant ly increased as compared with non-allodynic rats. The enhanced responses to mechanical and heat, but not to cold, stimulation were significantly reduc ed by CP-99994, a selective antagonist to tachykinin NK-1 receptors, When N GF was infused into the brain parenchyma (striatum, cortex and septum) no a llodynic nor hyperalgesic responses could be detected. These results indica te that in rats i.c.v. but not intraparenchymal infusion of NGF induce mech anical and cold allodynia as well as heat hyperalgesia, which is mediated, at least in part, by activation of NK-1 receptors. (C) 2000 Published by El sevier Science Ireland Ltd. All rights reserved.