Polyamidoamine dendrimer-conjugated triamcinolone acetonide attenuates nerve injury-induced mechanical allodynia by inhibiting spinal cord microglia activation

Abstract

Neuropathic pain is a pathological pain with allodynia and hyperalgesia that is caused by sensory neuron damage such as peripheral nerve injury (PNI). The activation of spinal cord microglia is critical for the development and maintenance of neuropathic pain after PNI. Previous study showed that triamcinolone acetonide (TA) inhibits microglia activation. However, TA has a limitation in clinical application due to its off-target side effects. To obviate this problem, I developed polyamidoamine (PAMAM) dendrimer-conjugated TA (D-TA), which supposedly delivers TA specifically into microglia. PAMAM dendrimer is a sphere-shape nano-molecule. In this study, I show that PAMAM-dendrimer is delivered selectively into spinal cord microglia. Intratheal D-TA injection inhibited nerve injury-induced spinal cord microglia activation. D-TA administration reduced mRNA expression of proinflammatory cytokines, such as Nox2, IL-1, TNF, and IL-6 in spinal cord after PNI. In addition, D-TA administration significantly attenuated PNI-induced mechanical allodynia. Conclusively, my data demonstrate that D-TA attenuates neuropathic pain after PNI by inhibiting spinal cord microglia activation, suggesting a therapeutic implication for the treatment of neuropathic pain.