The antinociceptive effects of a δ-opioid receptor agonist in mice with painful diabetic neuropathy: Involvement of heme oxygenase 1

The induction of the transcription factor Nrf2 enhances the antinociceptive effects of delta-opioid receptors in diabetic mice

“…Our data revealed that the subcutaneous administration of two specific DOR agonists, DPDPE and SNC-80, inhibited mechanical allodynia in a dose dependent manner. These results are consistent with previous studies, in which the central, spinal or systemic administration of DPDPE dose-dependently inhibited the mechanical and thermal hypersensitivity manifested in type 1 diabetic animals [20, 22, 41]. Our results supported these findings and further revealed the potential use of DOR agonists for the treatment of painful diabetic neuropathy associated to type 2 diabetes.…”

“…Accordingly, a recent work has demonstrated reduced mRNA expression of DOR in the spinal cord of type 2 diabetic monkeys [42]. Nevertheless, the fact that SFN treatment also activated the expression of HO-1 in db/db mice supported the idea that the improvement of the anti-allodynic actions of DOR agonists produced by SFN might be also consequence of the induction of HO-1, as occurs in animals with peripheral inflammation or type 1 diabetes [12, 22]. Nonetheless, the normalization of the sciatic nerve NQO1 proteins and the inhibition of JNK phosphorylation induced by the Nrf2 inductor might also contribute to enhance the anti-allodynic effects of DOR agonists in SFN treated mice.…”

“…In contrast to MOR agonists, some studies have demonstrated the potential antinociceptive effects produced by δ-opioid receptor (DOR) agonists in diabetic animals. Indeed, the intracerebroventricular, intrathecal and systemic administration of DOR agonists inhibited the nociceptive responses associated to type 1 diabetes in rodents [20–22]. A recent study has been also demonstrated that the antinociceptive effects produced by DOR agonists in streptozotocin-induced type 1 diabetes in mice were significantly increased by its co-treatment with an HO-1 inducer compound [22].…”

“…Indeed, the intracerebroventricular, intrathecal and systemic administration of DOR agonists inhibited the nociceptive responses associated to type 1 diabetes in rodents [20–22]. A recent study has been also demonstrated that the antinociceptive effects produced by DOR agonists in streptozotocin-induced type 1 diabetes in mice were significantly increased by its co-treatment with an HO-1 inducer compound [22]. Nonetheless, the role played by the systemic administration of DOR agonists on the mechanical allodynia observed in db/db mice and the effects produced by the Nrf2 transcription factor inducer (SFN) on the antinociceptive effects of DOR agonists and its expression in type 2 diabetic animals has not been assessed.…”

Delta opioid receptors are essential to the antiallodynic action of Β2-mimetics in a model of neuropathic pain

“…39 However, under neuropathic pain conditions, the administration of DOP receptor agonists has been shown to decrease mechanical and thermal pain modalities. [40][41][42][43][44] It has thus been suggested that DOP agonists may be of interest for pain treatment. Unfortunately, agonists of the DOP receptors cannot be presently used as appropriate clinical treatments for neuropathic pain.…”