[Role of neuronal nitric oxide synthase in dynorphin spinal neurotoxicity and analgesia in rats].

OBJECTIVE To investigate the different role of neuronal constitutive nitric oxide synthase (nc-NOS) in dynorphin (Dyn) A(1-17) spinal neurotoxicity and analgesia. METHODS The cNOS activity in ventral and dorsal spinal cord in rats was measured with H-L-arginine conversion, and ncNOS immunoreactivity(IR) was observed with strepavidin-peroxidase immunohisto-chemistry. RESULTS Intrathecal administration of Dyn A(1-17) produced dose-dependent paralysis of hindlimbs and tail as well as inhibition of tail flick (TF) and foot flinch (FF) reflexes. Dyn A(1-17) 10 nmol induced only transient paralysis and apparently reduced the ncNOS-IR in the superficial dorsal horn but did not induce any change of ncNOS-IR in the ventral horn cells as compared with saline control. Dyn A(1-17) 20 nmol produced permanent paraplegia with irreversible spinal cord damage, characterized by central and progressive necrosis. Dyn A(1-17) 20 nmol remarkedly induced the expression of ncNOS-IR in the ventral horn cells whereas inhibited ncNOS-IR in the superficial dorsal horn. Dyn A(1-17) 20 nmol also significantly increased the activities of cNOS in the ventral spinal cord but did not affect cNOS activities in the dorsal spinal cord. Intrathecal pretreatment with 7-nitroindazole (7-NI) 1 mumol, a selective ncNOS inhibitor 10 min prior to i.t. Dyn A(1-17) 20 nmol significantly ameliorated Dyn-induced neurological outcome, but TF and FF remained inhibited. 7-nitroindazole also significantly antagonized the increases of cNOS activities and ncNOS-IR in the ventral spinal cord at 4 h after i.t. Dyn A(1-17) 20 nmol, but did not affect or even potentiated Dyn-induced inhibition of cNOS activity and ncNOS-IR in the dorsal spinal cord. CONCLUSIONS Over-expression or over-activation of ncNOS in the ventral spinal cord may be involved in Dyn spinal neurotoxicity, whereas as the reduction of ncNOS activities in the dorsal spinal cord might reflect Dyn spinal analgeisia or pain modulation.