I am a
Home I AM A Search Login

Papers of the Week


Papers: 16 Nov 2019 - 22 Nov 2019


Animal Studies


2020 Jan 08


J Neurosci


40


2

Nerve Injury-Induced Neuronal PAP-I Maintains Neuropathic Pain by Activating Spinal Microglia.

Authors

Li J, Shi H, Liu H, Dong F, Liu Z, Lu Y, Chen L, Bao L, Zhang X
J Neurosci. 2020 Jan 08; 40(2):297-310.
PMID: 31744864.

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 dorsal root ganglion (DRG) of naïve rats but was expressed after peripheral nerve injury. However, its role in neuropathic pain remains unknown. We found that PAP-I expression was continuously up-regulated in the DRG neurons from rat spared nerve injury (SNI) models, and transported towards the spinal dorsal horn to act as a pro-inflammatory 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 SNI. Furthermore, PAP-I functioned by activating the spinal microglia via C-C chemokine receptor type 2 (CCR2) that participated in neuropathic pain. Inhibition of either microglial activation or CCR2 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.Neuropathic pain is maladaptive pain condition and the maintaining mechanism is largely unclear. Here we reveal that after peripheral nerve injury, PAP-I can be transported to the spinal dorsal horn and is crucial in the progression of neuropathic pain. Importantly, we prove that PAP-I mainly functions through activating the spinal microglia via CCR2-p38 MAPK pathway. Furthermore, we confirm that the pro-inflammatory effect of PAP-I is more prominent after the establishment of neuropathic pain, thus indicating that microglia also participates in the maintenance phase of neuropathic pain.