Conclusion
Intranasal administration of low doses of keta with DEX could be a new therapeutic approach to reduce neuropathic pain and consequently improve the quality of life of diabetic patients.
Methods
This work evaluated the antinociceptive effect of intranasal administration of the combination of dextro-ketamine (keta), a non-competitive glutamatergic receptor antagonist, and dexmedetomidine (DEX), a selective alpha2-adrenergic agonist, in rats with neuropathic pain induced by streptozotocin-DM.
Results
The thermal hyperalgesia and mechanical allodynia observed in DM model are reduced with the intranasal administration of the combination of keta and DEX (200 + 0.10 μg/kg) after 3 days of treatment. The antinociceptive action could be due to reduction of Ca2+ influx with lower glutamate release and reduced excitability through the activation of alpha2-adrenergic receptors by DEX and reduction of NMDA receptor activation by glutamate with lower excitability due to the antagonism produced by keta. DM induced increased expression of glial fibrillary acid protein (GFAP) and tumor necrosis factor-alpha (TNF-alpha) detected by immunohistochemistry, indicating greater astrocyte activity and intense inflammatory response. Intranasal administration for 10 days of the combination of low doses of keta and DEX promoted an intense decrease in the expression of both GFAP and TNF-alpha, indicating lower activation of astrocytes in the spinal cord and reduced production and release of TNF-alpha, favoring the reduction of inflammation.