Role of dorsal root ganglion K 2P 1.1 in peripheral nerve injury-induced neuropathic pain

Peripheral nerve injury-caused hyperexcitability and abnormal ectopic discharges in the primary sensory neurons of dorsal root ganglion (DRG) play a key role in neuropathic pain development and maintenance. The two-pore domain background potassium (K 2P ) channels have been identified as key determinants of the resting membrane potential and neuronal excitability. However, whether K 2P channels contribute to neuropathic pain is still elusive. We reported here that K 2P 1.1, the first identified mammalian K 2P channel, was highly expressed in mouse DRG and distributed in small-, medium-, and large-sized DRG neurons. Unilateral lumbar (L) 4 spinal nerve ligation led to a significant and time-dependent reduction of K 2P 1.1 mRNA and protein in the ipsilateral L4 DRG, but not in the contralateral L4 or ipsilateral L3 DRG. Rescuing this reduction through microinjection of adeno-associated virus-DJ expressing full-length K 2P 1.1 mRNA into the ipsilateral L4 DRG blocked spinal nerve ligation-induced mechanical, thermal, and cold pain hypersensitivities during the development and maintenance periods. This DRG viral microinjection did not affect acute pain and locomotor function. Our findings suggest that K 2P 1.1 participates in neuropathic pain development and maintenance and may be a potential target in the management of this disorder.