Peptide nucleic acids targeted to the mouse proNPFF(A) reveal an endogenous opioid tonus

Pharmacological studies have implicated the anti-opioid neuropeptide FF (NPFF) in the modulation of pain transmission. Since its physiological role has not yet been fully elucidated, the present study examined whether antisense peptide nucleic acid (PNA) complementary to the NPFF precursor (proNPFF(A)) modified pain sensitivity. Mice received three intraperitoneal (i.p.) injections (10mg/kg) of antisense PNA (As-proNPFF(A)) over a period of 24h. As-proNPFF(A) treatment significantly increased the basal tail withdrawal latency in the tail-flick test. This analgesia persisted during 2 days and was completely reversed by naloxone. Thus, antisense PNAs, by decreasing anti-opioid effects, revealed a basal endogenous opioid activity. Our results evidence a physiological interplay between NPFF and opioid systems and further support the use of PNA as effective antisense agents, for studying gene function in vivo.