Nerve injury-induced neuronal PAP-I maintains neuropathic pain by activating spinal microglia

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Abstract

Pancreatitis-associated proteins (PAPs) display multiple functions in visceral diseases. Previous studies showed that the expression level of PAP-I was low in the DRG of naive rats but was de novo expressed after peripheral nerve injury. However, its role in neuropathic pain remains unknown. We found that PAP-I expression was continuously upregulated in the DRG neurons from rat spared nerve injury models, and transported toward the spinal dorsal horn to act as a proinflammatory factor. Intrathecal delivery of PAP-I enhanced sensory hyperalgesia, whereas PAP-I deficiency by either gene knockout or antibody application alleviated tactile allodynia at the maintenance phase after spared nerve injury. Furthermore, PAP-I functioned by activating the spinal microglia via C-C chemokine receptor Type 2 that participated in neuropathic pain. Inhibition of either microglial activation or C-C chemokine receptor Type 2 abolished the PAP-I-induced hyperalgesia. Thus, PAP-I mediates the neuron-microglial crosstalk after peripheral nerve injury and contributes to the maintenance of neuropathic pain.

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Li, J., Shi, H., Liu, H., Dong, F., Liu, Z., Lu, Y., … Zhang, X. (2020). Nerve injury-induced neuronal PAP-I maintains neuropathic pain by activating spinal microglia. Journal of Neuroscience, 40(2), 297–310. https://doi.org/10.1523/JNEUROSCI.1414-19.2019

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