The imidazoline I 2 receptor agonist 2-BFI attenuates hypersensitivity and spinal neuroinflammation in a rat model of neuropathic pain

Chronic pain is a large, unmet public health problem. Recent studies have demonstrated the importance of neuroinflammation in the establishment and maintenance of chronic pain. However, pharmacotherapies that reduce neuroinflammation have not been successfully developed to treat chronic pain thus far. Several preclinical studies have established imidazoline I receptor (I R) agonists as novel candidates for chronic pain therapies, and while some I R ligands appear to modulate neuroinflammation in certain scenarios, whether they exert anti-neuroinflammatory effects in models of chronic pain is unknown. This study examined the effects of the prototypical I R agonist 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI) on hypersensitivity and neuroinflammation induced by chronic constriction injury (CCI), a neuropathic pain model in rats. In CCI rats, twice-daily treatment with 10 mg/kg 2-BFI for seven days consistently increased mechanical and thermal nociception thresholds, reduced GFAP and Iba-1 levels in the dorsal horn of the spinal cord, and reduced levels of TNF-α relative to saline treatment. These results were recapitulated in primary mouse cortical astrocyte cultures. Incubation with 2-BFI attenuated GFAP expression and supernatant TNF-α levels in LPS-stimulated cultures. These results suggest that I R agonists such as 2-BFI may reduce neuroinflammation which may partially account for their antinociceptive effects.