.png){kind=icon}
.png){kind=icon}
Return
Voltage-gated sodium channel 1.8 contributes to hyperalgesia induced by the coexistence of anxiety and remifentanil exposure
.png){kind=icon}
PRE
AI
C
L
Y
Y
Z
L
Z
J
DOI：10.3344/kjp.25273.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Background: Remifentanil-induced hyperalgesia (RIH) is directly mediated by altered mitochondrial dynamics. Moreover, anxiety is proven to worsen hyperalgesia. Voltage-gated sodium channel 1.8 (NaV1.8) is involved in both nociceptive initiation and anxiety. However, its role in modulating RIH, particularly in the coexistence of anxiety and RIH (CARIH), remains unexplored. Methods: A total of 148 Sprague-Dawley male rats were used to explore whether silencing NaV1.8 activation could alleviate CARIH. The behavioral effects were assessed using the open field, novelty suppressed feeding, and paw withdrawal tests. The mechanisms of antisense oligodeoxynucleotides (AS-ODN) targeting NaV1.8 (AS-NaV1.8) were investigated through western blot, RT-qPCR, electron microscopy, mitochondrial superoxide imaging, glutathione (GSH/GSSG) ratio, and malondialdehyde measurement. Results: NaV1.8 was upregulated at the mRNA level in the dorsal root ganglia (DRG) (P < 0.001) after CARIH. Meanwhile, spinal NR2B and Drp1 began to increase at 4 hours (P = 0.021) and 24 hours (P < 0.001), respectively. AS-NaV1.8 decreased spinal NR2B and Drp1 levels (P < 0.01), while increasing Mfn2 and OPA1 expression (P < 0.01). The MitoSox-positive cells in Group AS (AS-NaV1.8 injected into rats with CARIH) were fewer than those in Group AR (CARIH group) (P = 0.013) and Group MM (mismatch-ODN of NaV1.8 injected into rats with CARIH) (P = 0.018). Abnormal fission of spinal mitochondria was reduced in Group AS compared to Group AR (P = 0.023) and Group MM (P = 0.018). Conclusions: Anxiety exacerbates RIH, while NaV1.8 knockdown in DRG effectively attenuates CARIH by suppressing abnormal mitochondrial dynamics. Oral NaV1.8 inhibitors show promise in preclinical trials, suggesting NaV1.8 targeting as a novel approach to mitigate CARIH.
Keywords:
Anxiety
Ganglia, Spinal
Hyperalgesia
Mitochondria
Receptors, N-Methyl-D-Aspartate
Remifentanil
Voltage-Gated Sodium Channels
Journal
K
IF:
3.1
Papers:
484
Citations:
1.3K
Organization
Cited Papers