Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain

Abstract

Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the specific sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression increased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These findings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassium-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassium-chloride co-transporter 1.

Improving NKCC1 Function Increases the Excitability of DRG Neurons Exacerbating Pain Induced After TRPV1 Activation of Primary Sensory Neurons

“…In the second part, they were randomized into the control group, capsaicin group, and U0126 + capsaicin or GF109203X + capsaicin group. Bumetanide, U0126, and GF109203X are inhibitors of NKCC1, MEK/ERK, and PKC, respectively ( He et al, 2014 ).…”

“…The method of administering the inhibitors was as follows: capsaicin was injected subcutaneously 2 h after intrathecal injection of 20 μl of bumetanide (5 μg/μl) ( He et al, 2014 ; Gao et al, 2019 ). Then, 10 μl of U0126 (1 μg/μl) was administered intrathecally for 30 min before capsaicin was administered to the plantar ( Tian et al, 2020 ; Li Z. Y et al, 2017 ), while 20 μl of GF109203X (0.018 μg/μl) was administered intrathecally for 1.5 h before capsaicin was administered to the plantar ( Hang et al, 2017 ; Zhang et al, 2004 ).…”