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

Abstract

Experiments were conducted to explore the effects of Neuropeptide FF acting at spinal and supraspinal sites in models of chronic inflammatory or neuropathic pain and of acute pain. Neuropeptide FF was administered intrathecally (i.t.; 10.0, 25.0 and 50.0 nmol) or intracerebroventricularly (i.c.v.; 10.0, 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 sciatic nerve constriction. Evoked pain was assessed by measuring the withdrawal response threshold (in grams of pressure) to a mechanical stimulus applied to the plantar surface of the injured paw. Neuropeptide FF dose-dependently attenuated the allodynic response (i.e., withdrawal from a normally innocuous stimulus) to mechanical stimulation in the inflammatory and neuropathic model following i.t. (ED 50=20.86 nmol and ED 50=18.91 nmol, respectively) and i.c.v. (ED 50=12.31 nmol and ED 50=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 experiencing inflammatory, but not neuropathic pain. In contrast, Neuropeptide FF administered i.t. (10.0, 25.0 and 50.0 nmol) or i.c.v. (10.0, 12.5 and 15.0 nmol) had no effect on the response to acute thermal or mechanical stimulation. 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 Neuropeptide FF acting at spinal and supraspinal sites plays a role in modulating chronic, but not acute pain. Furthermore, the results suggest that the anti-allodynic effect of Neuropeptide FF is mediated indirectly by naloxone-sensitive opioid mechanisms in rats subjected to inflammatory, but not neuropathic pain.