Intrathecal administration of PNA targeting galanin receptor reduces galanin-mediated inhibitory effect in the rat spinal cord

Peptide nucleic acids (PNA) are nucleic acid analogues containing neutral a mide backbone, forming stable and tight complexes with complementary DNA/RN A. However, it is unclear whether unmodified PNA can efficiently penetrate neuronal tissue in order to act as antisense reagent. Here we show that int rathecal (i.t.) injection of an unmodified antisense PNA complementary to t he rat galanin receptor type I (GalRI) mRNA is able to block the inhibitory effect of i.t. administered galanin on spinal nociceptive transmission. Au toradiographic ligand binding studies using [I-125]galanin show that the un modified PNA is able to reduce the density of galanin binding sites in the dorsal horn. Thus, unmodified PNA applied i.t. appears to function as an ef fective antisense reagent in rat spinal cord in vivo. NeuroReport 12:317-32 0 (C) 2001 Lippincott Williams & Wilkins.