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Papers of the Week

Papers: 10 Dec 2022 - 16 Dec 2022

2022 Dec 09


HAP1 inhibition contributes to neuropathic pain by suppressing Cav1.2 activity and attenuating inflammation.


Pan JY, Zhao YY, Sang R, Yang RY, Bao J, Wu Y, Fei Y, Wu J, Chen G
Pain. 2022 Dec 09.
PMID: 36508175.


Although pain dysfunction is increasingly observed in Huntington disease (HD), the underlying mechanisms still unknown. As a crucial huntington-associated protein, HAP1 is enriched in normal spinal dorsal horn and dorsal root ganglia (DRG) where are regarded as "primary sensory center", indicating its potential functions in pain process. Here, we discovered that HAP1 level was greatly increased in the dorsal horn and DRG under acute and chronic pain conditions. Lack of HAP1 obviously suppressed mechanical allodynia and hyperalgesia in spared nerve injury (SNI)- and chronic constriction injury (CCI)-induced pain. Its deficiency also greatly inhibited the excitability of nociceptive neurons. Interestingly, we found that suppressing HAP1 level diminished the membrane expression of the L-type calcium channel (Cav1.2), which can regulate Ca2+ influx and then influence BDNF synthesis and release. Furthermore, SNI-induced activation of astrocytes and microglia notably decreased in HAP1 deficient mice. These results indicate that HAP1 deficiency might attenuate pain responses. Collectively, our results suggest that HAP1 in dorsal horn and DRG neurons regulates Cav1.2 surface expression, which in turn reduces neuronal excitability, BDNF secretion and inflammatory responses and ultimately influences neuropathic pain progression.