Neuropeptide FF attenuates allodynia in models of chronic inflammation andneuropathy following intrathecal or intracerebroventricular administration

Experiments were conducted to explore the effects of Neuropeptide FF acting at spinal and supraspinal sites in models of chronic inflammatory or neuro pathic pain and of acute pain. Neuropeptide FF was administered intrathecal ly (i.t.; 10.0, 25.0 and 50.0 nmol) or intracerebroventricularly (i.c.v.; 1 0.0, 12.5 and 15.0 nmol) either 24 h after inflammation-inducing injections of Freund's Complete Adjuvant in one hind paw or 7 days after unilateral s ciatic nerve constriction. Evoked pain was assessed by measuring the withdr awal response threshold (in grams of pressure) to a mechanical stimulus app lied to the plantar surface of the injured paw. Neuropeptide FF dose-depend ently attenuated the allodynic response (i.e., withdrawal from a normally i nnocuous stimulus) to mechanical stimulation in the inflammatory and neurop athic model following i.t. (ED50 = 20.86 nmol and ED50 = 18.91 nmol, respec tively) and i.c.v. (ED50 = 12.31 nmol and ED50 = 11.68 nmol, respectively) administration. Pretreatment with naloxone (2.0 mg/kg; s.c.) attenuated the anti-allodynic effect of i.t. or i.c.v. Neuropeptide FF in rats experienci ng inflammatory, but not neuropathic pain. In contrast, Neuropeptide FF adm inistered i.t. (10.0, 25.0 and 50.0 nmol) or i.c.v. (10.0, 12.5 and 15.0 nm ol) had no effect on the response to acute thermal or mechanical stimulatio n. Neuropeptide FF injected i.t. or i.c.v, in inflamed or neuropathic rats did not produce any sign of motor dysfunction. These results suggest that N europeptide FF acting at spinal and supraspinal sites plays a role in modul ating chronic, but not acute pain. Furthermore, the results suggest that th e anti-allodynic effect of Neuropeptide FF is mediated indirectly by naloxo ne-sensitive opioid mechanisms in rats subjected to inflammatory, but not n europathic pain. (C) 2000 Elsevier Science B.V. All rights reserved.