Alleviation of neuropathic pain by over-expressing a soluble colony-stimulating factor 1 receptor

Abstract

In this study, we aim to alleviate neuropathic pain by suppressing microgliosis and macrophage accumulation, which is achieved by over-expressing a non-functional soluble colony-stimulating factor 1 receptor using adeno-associated virus 9 vectors (AAV9/sCSF1R). AAV9/sCSF1R and AAV9/GFP were intrathecally administered into mouse lumbar spine. Two weeks later, these mice underwent partial sciatic nerve ligation to induce neuropathic pain. GFP and sCSF1R were highly expressed in dorsal root ganglia (DRG) and spinal cords in AAV9-injected mice. Nerve ligation alone or pre-treated with AAV9/GFP led to significant microgliosis in the lumbar spinal cords and macrophage accumulation in DRG and sciatic nerves. In nerve-ligated mice pre- treated with AAV9/sCSF1R the microglia densities in the dorsal and ventral horns and macrophage densities in DRG and sciatic nerves were significantly lower compared to nerve-ligated mice pre-treated with AAV9/GFP. Behavioural tests showed that nerve-ligated mice pre- treated with AAV9/sCSF1R had a significantly higher paw withdrawal threshold, indicating the alleviation of neuropathic pain. The results implicate that viral vector-mediated expression of sCSF1R may represent a novel strategy in long-term alleviation of neuropathic pain.