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Papers of the Week

Papers: 18 May 2019 - 24 May 2019

Animal Studies

2019 Jul 17

J Neurosci



Protein kinase C lambda mediates acid-sensing ion channel 1a-dependent cortical synaptic plasticity and pain hypersensitivity.


Li H-S, Su X-Y, Song X-L, Qi X, Li Y, Wang R-Q, Maximyuk O, Krishtal O, Wang T, Fang H, Liao L, Cao H, Zhang Y-Q, Zhu MX, Liu M-G, Xu T-L
J Neurosci. 2019 Jul 17; 39(29):5773-5793.
PMID: 31101759.


Chronic pain is a serious debilitating disease for which effective treatment is still lacking. Acid-sensing ion channel 1a (ASIC1a) has been implicated in nociceptive processing at both peripheral and spinal neurons. However, whether ASIC1a also contributes to pain perception at the supraspinal level remains elusive. Here, we report that ASIC1a in anterior cingulate cortex (ACC) is required for thermal and mechanical hypersensitivity associated with chronic pain. ACC-specific genetic deletion or pharmacological blockade of ASIC1a reduced the probability of cortical long-term potentiation (LTP) induction and attenuated inflammatory thermal hyperalgesia and mechanical allodynia in male mice. Using cell type-specific manipulations, we demonstrate that ASIC1a in excitatory neurons of ACC is a major player in cortical LTP and pain behavior. Mechanistically, we show that ASIC1a tuned pain-related cortical plasticity through protein kinase C lambda-mediated increase of membrane trafficking of AMPA receptor subunit GluA1 in ACC. Importantly, post-application of ASIC1a inhibitors in ACC reversed previously established nociceptive hypersensitivity in both chronic inflammatory pain and neuropathic pain models. These results suggest that ASIC1a critically contributes to higher level of pain processing through synaptic potentiation in ACC, which may serve as a promising analgesic target for treatment of chronic pain. Chronic pain is a debilitating disease that still lacks effective therapy. Ion channels are good candidates for developing new analgesics. Here, we provide several lines of evidence to support an important role of cortically-located ASIC1a channel in pain hypersensitivity through promoting long-term synaptic potentiation in the anterior cingulate cortex. Our results indicate a promising translational potential of targeting ASIC1a to treat chronic pain.