NEUROPATHIC PAIN IN RATS IS ASSOCIATED WITH ALTERED NITRIC-OXIDE SYNTHASE ACTIVITY IN NEURAL TISSUE

Peripheral nerve injury may lead to a chronic neuropathic pain state t hai results from an increase in excitability of central neurons, This central sensitization is mediated via an N-methyl-D-aspartic acid (NMD A) receptor and may involve the production of nitric oxide (NO), As NO is suggested to play a role in nociceptive transmission following ner ve injury, we examined for altered NO synthase activity at multiple le vels of peripheral and spinal neural tissue in a rat model of neuropat hic pain. Peripheral neuropathy was induced in rats (N = 12) by ligati on of the left L5 and Lb nerve roots. Six other rats had sham surgery. An ipsilateral decrease in paw withdrawal threshold to mechanical sti muli confirmed the presence of a neuropathic pain state. Samples oi th e lumbar and thoracic spinal cords, L4, L5, and L6 dorsal root ganglia (DRGs), and the sciatic nel?les were obtained from the lesioned and c ontralateral sides al 2 and 4 weeks after neuropathic surgery (N = 6 p er group). Tn the lumbar spinal cord, a bilateral decrease in nitric o xide synthase (NOS) activity was observed :! and 4 weeks after neuropa thic surgery. NOS activity Ei as increased in the ipsilateral L5 and 6 DRGs 2 weeks following neuropathic surgery. An increase in NOS activi ty in the DRG ma! be an early mechanism for inducing more central chan ges, The bilaterally decreased NOS activity in the lumbar spinal cord may be secondary to a negative feedback mechanism resulting from incre ased NO production in the spinal dor sal root ganglia. Multiple altera tions in expression of NOS activity that occur in both peripheral and central processing may play a role in the pain behavior resulting fi o m peripheral naive injury.