The Role Of NOS In Nociceptive Processing And Hyperalgesia In The Spinal Cord Of The Rat During Formalin-induced Inflammatory Pain

The release of excitatory amino acids(EAAs) and up-regulation or increase in activation of EAAs receptor in pathway of nociceptive information can contribute to pain and hyperalgesia.Nitric oxide (NO) is a key mediator of nociceptive activity in numerous animal models used to study pain. Inhibiting NO production by administering a nitric oxide synthase (NOS) inhibitor diminishes nociceptive behaviors in a variety of pain models. More relevant to the present study, NO is not normally present in its free radical form in the mammalian body and must be synthesized in a process involving NOS, NOS exists in one of three isoforms, two constitutive isoforms that are always present within the body (neuronal and endothelial NOS) and a third isoform that is not normally present and must be synthesized de novo (inducible NOS). Neuronal NOS (nNOS) and endothelial NOS (eNOS) is commonly found in a variety of cell types including macrophages, chondrocytes and neutrophiles. Recently investigators have begun to study the effects of selective inhibitors of the different NOS isoforms on nociceptive processing. This preliminary evidence suggeststhat NO contributes to nociception after peripheral injury; however, since thus studies has used different nociceptive models and different routes of administration for the NOS inhibitors, it is difficult to establish the relative role of the different NOS isforms in either peripheral or spinal nociceptive mechanisms. The purpose of the present study was initially to first determine the effect of i.t. administritionof NOS and iNOS inhibitors on Formalin-induced infalammatroy pain and which NOS isoforms played a significant role in the spinal cord.1 NOS isoform and its time course in the dorsal horn of the spinal cord during formalin-induced inflammatory pain and hyperalgesia in rat.Thirty SD rarts were divided into five groups: control ,8h,12h,24h,48h group.The inflammatory pain and hyperalgesia were induced by subcutaneous injection of 2.5%formalin solution (O.lml) in the right hind paw. Two of three NOS isoforms were detected by immunhistochemical method. As compared with control group, nNOS was constitutively expressed in dorsal horn neurons of the spinal cord in the superficial laminae I-IV. Inflammatory stimulation resulted in a time dependent statistically significant increase of nNOS immunoreactive cells in the dorsal horns of both the ipsi- and contralateral side. On the ipsilateral side this increase occurred earlier and was somewhat more pronounced. The expression of iNOS in thedorsal and ventral horns of the spinal cord were increased after hind-paw injection of formalin, and the increases were the most obvious in 24h after the injection. In addition, we demonstrate here that iNOS is highly upregulated. In contrast to nNOS, however iNOS was exclusively found in activated astrocytes.The results indicated that during inflammatory pain and hyperalgesia, both nNOS and iNOS have an increase at the spinal cord. Furthemore, the significant isoform of NOS in rat dorsal horn of the spinal cord is iNOS and it increased with time course. The increase is the most obvious in 24h group.2 The influence of the selective iNOS inhibitor and the non-selective NOS inhibitor about the nociceptive threshold of the rat during the formalin-induced inflammatory pain and hyperalgesia.Thirty SD rats were divided into five groups: Formalin group, AG(1) group, AG(2) group, L-NNA(l) group and L-NNA(2) group. The single formalin group were injected O.lml of formalin (2.5% in saline) subcutaneously into the planter aspect of right hindpaw. The rats of AG(1) group and AG(2) group were first intrathecally injected AG (1 u mol in 10 u 1 normal saline (NS)) followed by 10 u 1 NS to flush the catheter with its contents. The injection was conducted slowly over 30s. Twenty minutes later O.lml formalin (2.5% in saline) was injected.The L-NNA(l) group and L-NNA(2)group just like the last two groups but the difference of Nw-nitro-L-arginine (L-NNAlOnmol in lul Ns). Then observed its...