Role of α2-adrenoceptors in enhancement of antinociceptive effect in diabetic mice

Abstract

The present studies investigated behavioral and neurochemical aspects of the noradrenergic and serotonergic nervous systems in streptozotocin-induced diabetic mice.We previously reported that intrathecal (i.t.) injection of norepinephrine significantly potentiated antinociception in diabetic mice compared to that in non-diabetic mice, and that antinociception due to norepinephrine injection was completely abolished by pretreatment with yohimbine, an α 2 -adrenoceptor antagonist. The present studies demonstrated that i.t. injection of clonidine also showed more potent antinociceptive activity in diabetic mice than in non-diabetic mice, but that i.t. methoxamine injection did not affect diabetic or non-diabetic mice. The antinociceptive potency due to i.t.injection of 5-HT was significantly lower in diabetic than in non-diabetic mice. In a neurochemical study, we found that the density of

Increased Presynaptic and Postsynaptic α2-Adrenoceptor Activity in the Spinal Dorsal Horn in Painful Diabetic Neuropathy

“…The mechanisms underlying increased ␣ 2 -adrenoceptor activity in the spinal cord in diabetic neuropathy are not fully known. It has been reported that diabetic neuropathy reduces the norepinephrine release and causes a compensatory up-regulation of the ␣ 2 -adrenoceptor in the spinal cord (Omiya et al, 2008). Nevertheless, because the endogenous ligand for ␣ 2 -adrenoceptors may be reduced in diabetic rats, this could explain why the baseline glutamate release at the spinal level is still elevated in diabetic rats.…”

“…Many experimental studies have demonstrated that intrathecal or systemic administration of ␣ 2 -adrenoceptor agonists can produce a potent analgesic effect in neuropathic pain caused by traumatic nerve injury and diabetic neuropathy (Courteix et al, 1994;Yaksh et al, 1995;Calcutt and Chaplan, 1997;Buerkle and Yaksh, 1998;Pan et al, 1999;Omiya et al, 2008). In addition, clinical studies have shown that spinally administered ␣ 2 -adrenoceptor agonists reduce the intractable neuropathic pain caused by nerve injury and cancer (Rauck et al, 1993;Hassenbusch et al, 2002).…”

Venlafaxine and Neuropathic Pain

“…Antidepressants with dual inhibition of 5-HT and NA are more effective than selective compounds in the treatment of NP in rats [21,22]. Moreover, it was also demonstrated that intrathecal injection of NA or 5-HT produced a strong antinociceptive effect in STZ-treated rodents [23][24][25]. The antinociceptive effects of VFX depend on the administered doses.…”

Preventive and Alleviative Effect of Tramadol on Neuropathic Pain in Rats: Roles of α2-Adrenoceptors and Spinal Astrocytes

“…The analgesic effect of tramadol on neuropathic pain is considered to be at least partly due to its interaction with presynaptic and postsynaptic a 2 -ARs located on the central terminals of primary nociceptive afferents and the spinal dorsal horn neurons, respectively (35 -37). The analgesic potency of tramadol (26), as well as a 2 -AR agonists (38,39), is enhanced in neuropathic pain, probably due to the increased activity of presynaptic and postsynaptic a 2 -ARs (40). Thus, the present results do not exclude the possibility that the analgesic effect of tramadol on neuropathic pain is partly mediated through a 2 -ARs.…”