Low dose alpha-2 antagonist paradoxically enhances rat norepinephrine and clonidine analgesia.
- Author(s): Milne, Brian;
- Sutak, Maaja;
- Cahill, Catherine M;
- Jhamandas, Khem
- et al.
Published Web Locationhttps://doi.org/10.1213/ane.0b013e3182121bae
Ultralow-dose opioid antagonists prolong opioid antinociception and block tolerance. In this study we determined whether low doses of the α-2 adrenergic receptor (A2-R) antagonist, atipamezole, similarly influenced A2-R-induced antinociception and tolerance. In rats, intrathecal norepinephrine (NE) or clonidine in combination with atipamezole was tested using tail-flick and paw pressure tests. Acute tolerance to NE was induced by serial injections. Low-dose atipamezole significantly prolonged NE and clonidine-induced antinociception. Coadministration of atipamezole with A2-R agonists also prevented loss of agonist potency in the acute tolerance model. This study demonstrates paradoxical effects of low-dose A2-R antagonists augmenting A2-R agonist-induced analgesia.