Nerve Injury-Induced Neuronal PAP-I Maintains Neuropathic Pain by Activating Spinal Microglia
| Autor: | Luonan Chen, Jia-Yin Li, Lan Bao, Haixiang Shi, Ying-Jin Lu, Zhi-Ping Liu, Fei Dong, Xu Zhang, Hui Liu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male SNi Pancreatitis-Associated Proteins Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences Chemokine receptor 0302 clinical medicine Peripheral Nerve Injuries Ganglia Spinal medicine Animals Neurons Microglia business.industry General Neuroscience Nerve injury Rats Protein Transport 030104 developmental biology medicine.anatomical_structure Spinal Cord Hyperalgesia Neuropathic pain Peripheral nerve injury Neuralgia medicine.symptom Erratum business Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 40(2) |
| ISSN: | 1529-2401 |
| Popis: | 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 wasde novoexpressed 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.SIGNIFICANCE STATEMENTNeuropathic 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 the CCR2-p38 MAPK pathway. Furthermore, we confirm that the proinflammatory effect of PAP-I is more prominent after the establishment of neuropathic pain, thus indicating that microglia also participate in the maintenance phase of neuropathic pain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|