Induction of spinal cord neuronal nitric oxide synthase (NOS) after formalin injection in the rat hind paw

The nitric oxide synthase (NOS) inhibitor t,-nitroarginine methyl ester has been found to exhibit antinociceptive activity in a rat model of pain [Kitto, K.F. et al., Neurosci. Lett., 148 (1992) 1–5; Lee, J.H. et al., NeuroReport, 3 (]992) 841–844; Moore, P.K. et al., Br. J. Pharmacol., 102 (1991) 198–202]. We investigated the hypothesis that hind paw injection of formalin increases the number of dorsal horn neuronal nitric oxide synthase (nNOS) containing neurons. Results showed a bilateral increase in the number of nNOS-positive neurons at the L4–5 dorsal horn area following formalin injection. The increase was always greater on the ipsilateral side compared to the contralateral side. This upregulation of nNOS following formalin stimulation of the hind paw suggested that nitric oxide (NO) may play a role in the central mechanism of hyperalgesia that follows peripheral inflammation.