Freire et al. Distribution of reduced-nicotina- mide-adenine-dinucleotide-phos- phate diaphorase-positive cells and ﬁbers in the cat central nervous sys- tem. J. Comp. Neurol. 279, 281–311. Moncada, S., Palmer, R. M., and Higgs, E. A. (1989). The biological signiﬁcance of nitric oxide formation from L-arginine. Biochem. Soc. Trans. 17, 642–644. Moreira, P. I., Smith, M. A., Zhu, X., Nunomura, A., Castellani, R. J., and Perry, G. (2005). Oxidative stress and neurodegeneration. Ann. N. Y. Acad. Sci. 1043, 545–552. Moreno-Lopez, B., Noval, J.A., Gonzalez- Bonet, L. G., and Estrada, C. (2000). Morphological bases for a role of nitric oxide in adult neurogenesis. Brain Res. 869, 244–250. Pacher, P., Beckman, J. S., and Liaudet, L. (2007). Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 87, 315–424. Palmer, R. M., Ferrige, A. G., and Moncada, S. (1987). Nitric oxide release accounts for the biological activity of endothelium-derived relax- ing factor. Nature 327, 524–526. Parkinson, J. (2000). Nitric oxide syn- thase inhibitors I: substrate analogs and heme ligands. In Nitric Oxide, B. Mayer, ed. (Berlin, Springer), pp. 112–129. Pereira,A.,Jr.,Freire,M.A.M.,Bahia, C. P., Franca, J. G., and Picanço-Diniz, C.W. (2000). The barrel ﬁeld of the adult mouse SmI cortex as revealed by NADPH-diaphorase histochemistry. Neuroreport 11, 1889–1892. Qian, Y., Chao, D. S., Santillano, D. R., Cornwell, T. L., Nairn, A. C., Greengard, P., Lincoln, T. M., and Bredt, D. S. (1996). cGMP-dependent protein kinase in dorsal root ganglion: relationship with nitric oxide synthase and nociceptive neurons. J. Neurosci. 16, 3130–3138. Ruschewe yh, R., Gor alczyk, A., Wunderbaldinger, G., Schober, A., and Sandkuhler, J. (2006). Possible sources and sites of action of the nitric oxide involved in synaptic plasticity at spinal lamina I projection neurons. Neuroscience 141, 977–988. Saha, R. N., and Pahan, K. (2006). Signals for the induction of nitric oxide syn- thase in astrocytes. Neurochem. Int. 49, 154–163. Sandell, J. H. (1986). NADPH diapho- rase histochemistry in the macaque striate cortex. J. Comp. Neurol. 251, 388–397. Scherer-Singler, U., Vincent, S. R., Kimura, H., and McGeer, E. G. (1983). Demonstration of a unique population of neurons with NADPH- diaphorase histochemistry. J. Neurosci. Meth. 9, 229–234. Schmidtko,A.,Gao,W.,Konig,P.,Heine,S., Motterlini,R.,Ruth, P.,Schlossmann, J., Koesling, D., Niederberger, E., Tegeder, I.,Friebe, A.,and Geisslinger,G.(2008). cGMP produced by NO-sensitive gua- nylyl cyclase essentially contributes to inﬂammatory and neuropathic pain by using targets different from cGMP- dependent protein kinase I. J. Neurosci. 28, 8568–8576. Silvius, K. M., and Fragoso, J. M.V. (2003). Red-rumped agouti (Dasyprocta lepo- rina) home range use in an Amazonian forest: implications for the aggregated distribution of forest trees. Biotropica 35, 74–83. Stojkovic, T., Colin, C., Le Saux, F., and Jacque, C. (1998). Speciﬁc pattern of nitric oxide synthase expression in glial cells after hippocampal injury. Glia 22, 329–337. Stuehr, D. J., and Grifﬁth, O. W. (1992). Mammalian nitric oxide synthases. Adv. Enzymol. 65, 287–346. Stuehr, D. J., Santolini, J., Wang, Z. Q., Wei, C. C., and Adak, S. (2004). Update on mechanism and catalytic regula- tion in the NO synthases. J. Biol. Chem. 279, 36167–36170. Tanabe, M., Nagatani, Y., Saitoh, K., Takasu, K., and Ono, H. (2009). Pharmacological assessments of nitric oxide synthase isoforms and downstream diversity of NO signal- ing in the maintenance of thermal and mechanical hypersensitivity after peripheral nerve injury in mice. Neuropharmacology 56, 702–708. Tang, Q., Svensson, C. I., Fitzsimmons, B., Webb, M., Yaksh, T. L., and Hua, X. Y. (2007). Inhibition of spinal constitu- tive NOS-2 by 1400W attenuates tis- sue injury and inﬂammation-induced hyperalgesia and spinal p38 activation. Eur. J. Neurosci. 25, 2964–2972. Tao, Y. X., Hassan, A., Haddad, E., and Johns, R. A. (2000). Expression and action of cyclic GMP-dependent protein kinase Ialpha in inﬂamma- tory hyperalgesia in rat spinal cord. Neuroscience 95, 525–533. Thomas, E., and Pearse, A. G. (1964). The solitary active cells. Histochemical demonstration of damage-resistant nerve cells with a TPN-diaphorase reaction. Acta Neuropathol. (Berl) 27, 238–249. Toda, N., Ayajiki, K., and Okamura, T. (2005). Nitric oxide and penile erec- tile function. Pharmacol. Ther. 106, 233–266. Todd, A. J., Puskar, Z., Spike, R. C., Hughes, C., Watt, C., and Forrest, L. (2002). Projection neurons in lamina I of rat spinal cord with the neurokinin 1 receptor are selectively innervated by substance p-containing afferents and respond to noxious stimulation. J. Neurosci. 22, 4103–4113. Valtschanoff, J. G., Weinberg, R. J., Kharazia, V. N., Schmidt, H. H., Nakane, M., and Rustioni, A. (1993). Neurons in rat cerebral cortex that synthesize nitric oxide: NADPH diaphorase histochemistry, NOS immunocytochemistry, and colocali- zation with GABA. Neurosci. Lett. 157, 157–161. Valtschanoff, J. G., Weinberg, R. J., and Rustioni,A. (1992a). NADPH diapho- rase in the spinal cord of rats. J. Comp. Neurol. 321, 209–222. Valtschanoff, J. G., Weinberg, R. J., Rustioni, A., and Schmidt, H. H. (1992b). Nitric oxide synthase and GABA colocalize in lamina II of rat spinal cord. Neurosci. Lett. 148, 6–10. Vincent, S. R. (1994). Nitric oxide: a radi- cal neurotransmitter in the central nervous system. Prog. Neurobiol. 42, 129–160. Vincent, S. R., and Hope, B. T. (1992). Neurons that say NO. Trends Neurosci. 15, 108–113. Wall, P. D., Kerr, B. J., and Ramer, M. S. (2002). Primary afferent input to and receptive ﬁeld properties of cells in rat lumbar area X. J. Comp. Neurol. 449, 298–306. Wall, P. D., and Woolf, C. J. (1984). Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the ﬂexion reﬂex in the rat. J. Physiol. 356, 443–458. Wallace, M. N., Tayebjee, M. H., Rana, F. S., Farquhar, D. A., and Nyong’o, A. O. (1996). Pyramidal neurones in patho- logical human motor cortex express nitric oxide synthase. Neurosci. Lett. 212, 187–190. Wiencken, A. E., and Casagrande, V. A. (2000). The distribution of NADPH diaphorase and nitric oxide synthetase (NOS) in relation to the functional compartments of areas V1 and V2 of primate visual cortex. Cereb. Cortex 10, 499–511. Wiesinger, H. (2001). Arginine metabo- lism and the synthesis of nitric oxide in the nervous system. Prog. Neurobiol. 64, 365–391. Willis, W. D., Al-Chaer, E. D., Quast, M. J., and Westlund, K. N. (1999). A visceral pain pathway in the dorsal column of the spinal cord. Proc. Natl. Acad. Sci. U.S.A. 96, 7675–7679. Wink, D. A., Miranda, K. M., and Espey, M. G. (2000). Effects of oxida- tive and nitrosative stress in cytotoxic- ity. Semin. Perinatol. 24, 20–23. Woolf, C. J. (1983). Evidence for a central component of post-injury pain hypersensitivity. Nature 306, 686–688. Wu, J., Su, G., Ma, L., Zhang, X., Lei, Y., Li, J., Lin, Q., and Fang, L. (2005). Protein kinases mediate increment of the phosphorylation of cyclic AMP- Nitric oxide and pain responsive element binding protein in spinal cord of rats following capsaicin injection. Mol. Pain 1, 26. Xiao,Y. M., Diao,Y. C., and So, K. F. (1996). A morphological study of neurons expressing NADPH diaphorase activity in the visual cortex of the golden ham- ster. Brain Behav. Evol. 48, 221–230. Yan, X. X., and Garey, L. J. (1997). Morphological diversity of nitric oxide synthesising neurons in mam- malian cerebral cortex. J. Brain Res. 38, 165–172. Yan, X. X., Jen, L. S., and Garey, L. J. (1996). NADPH-diaphorase-positive neurons in primate cerebral cortex colocalize with GABA and calcium-binding pro- teins. Cereb. Cortex 6, 524–529. Yo n e h a r a , N . , Ta k e m u r a , M . , Yoshimura, M., Iwase, K., Seo, H. G., Taniguchi, N., and Shigenaga, Y. (1997). Nitric oxide in the rat spinal cord in Freund’s adjuvant-induced hyperalgesia. Jpn. J. Pharmacol. 75, 327–335. Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any com- mercial or financial relationships that could be construed as a potential conﬂict of interest. Received: 05 May 2009; paper pending pub- lished: 10 June 2009; accepted: 08 July 2009; published: 15 September 2009. Citation: Front. Neurosci. (2009) 3, 2: 175- 181. doi: 10.3389/neuro.01.024.2009 Copyright © 2009 Freire, Guimarães, Leal and Pereira. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unre- stricted use, distribution, and reproduc- tion in any medium, provided the original authors and source are credited. Frontiers in Neuroscience www.frontiersin.org September 2009 | Volume 3 | Issue 2 | 181