Abstract
Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats. CX3CR1 siRNA-treated rats exhibited significant reductions in the activation of microglia in the spinal dorsal horn and a downregulation of proinflammatory mediators, as well as a significant attenuation of mechanical allodynia. These data indicate that the PLGA-encapsulated CX3CR1 siRNA nanoparticles effectively reduce neuropathic pain in SNL-induced rats by reducing microglial activity and the expression of proinflammatory mediators. Therefore, we believe that PLGA-encapsulated CX3CR1 siRNA nanoparticles represent a valuable new treatment option for neuropathic pain.
Highlights
Neuropathic pain is caused by various lesions or diseases of the somatosensory system [1]
We examined the use of PLGA-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles for the treatment of neuropathic pain in an spinal nerve ligation (SNL) model
We investigated whether PLGA-encapsulated CX3CR1 siRNA nanoparticles can reduce pain behavior in SNL-induced neuropathic pain rats
Summary
Neuropathic pain is caused by various lesions or diseases of the somatosensory system [1]. When a nerve is damaged, neurotransmitters such as glutamate, ATP, and substance P are released form presynaptic terminals of the primary afferent neurons in the dorsal root ganglia [3]. Release of these neurotransmitters causes nociceptive pain by depolarizing postsynaptic neurons in the spinal cord [4]. These molecules subsequently bind to the corresponding receptors of the glia and microglia of the dorsal horn of the spinal cord and activate the microglia [5], leading to the release of various cytokines and other diffusible molecules in the activated microglia, exacerbating the symptoms of the disease [6]
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