The noradrenergic pathway of the DAS has been suggested to be important for intrinsic antinociception in a neuropathic pain state and its facilitation may lead to anti-hyperalgesia, because noradrenergic neurons in the LC are activated in peripheral nerve-injured rats [
13]. Furthermore, an α
2-adrenergic agonist potentiates the antinociceptive effect of SCS [
24]. By this study, we showed that the intrathecally administered α
2-adrenergic receptor antagonist completely abolished the antinociceptive effect of SCS. In addition, we found that the immunoreactivity of DβH in the ipsilateral LC of injured rats significantly increased but was restored by 3-h SCS, although the LC neurons were not activated by SCS in SNL rats. Similarly, unilateral nerve injury does not influence the number of Fos-positive neurons in the LC if innocuous mechanical stimuli are not applied [
38]. Immunohistochemical changes in the LC region in neuropathic animal models are controversial. Previous studies showed that unilateral nerve injury induces bilateral activation or excitability of LC neurons [
13,
38,
39]; however, another study showed that DβH-positive neurons were increased in the LC on the ipsilateral side to sciatic nerve injury [
14]. The LC receives only little input from fibers of the DRN, although noradrenergic neurons in the LC project to almost all the regions in the CNS [
37]. Bilateral activation of noradrenergic neurons in the LC may be explained by projection from the DRN to both sides of the LC [
37,
40]. We could not determine why the increase in DβH immunoreactivity was ipsilateral. However, the differences in the ratio of DβH expression in the LC among the three groups were relatively small and intrathecal administration of idazoxan without SCS did not alter ipsilateral PWT. The results of the behavioral experiment agree with the evidence that chronic pain does not elicit tonic activity of LC neurons and secretion of norepinephrine in the spinal cord [
38,
40,
41]. Therefore, the expression change of DβH in the ipsilateral LC may only have a minor effect on the noradrenergic pathway of the DAS. However, further research is needed to elucidate the roles of LC activation in the modulation of the noradrenergic antinociceptive pathway.