English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Systemically administered dexmedetomidine (DEX), a selective α2 adrenergic receptor (α2-AR) agonists, produces analgesia and sedation. Peripherally restricted α2-AR antagonist could block the analgesic effect of systemic DEX on neuropathic pain, with no effect on sedation, indicating peripheral analgesic effect of DEX. Tetrodotoxin-resistant (TTX-R) sodium channel Na v 1.8 play important roles in the conduction of nociceptive sensation. Both α2-AR and Nav1.8 are found in small nociceptive DRG neurons. We, therefore, investigated the effects of DEX on the Na v 1.8 currents in acutely dissociated small-diameter DRG neurons.    Results  Whole-cell patch-clamp recordings demonstrated that DEX concentration-dependently suppressed TTX-R Na v 1.8 currents in small-diameter lumbar DRG neurons. DEX also shifted the steady-state inactivation curves of Na v 1.8 in a hyperpolarizing direction and increased the threshold of action potential and decrease electrical and chemical stimuli-evoked firings in small-diameter DRG neurons. The α2-AR antagonist yohimbine or α2 A -AR antagonist BRL44408 but not α2 B -AR antagonist imiloxan blocked the inhibition of Na v 1.8 currents by DEX. Immunohistochemistry results showed that Na v 1.8 was predominantly expressed in peripherin-positive small-diameter DRG neurons, and some of them were α2 A -AR-positive ones. Our electrophysiological recordings also demonstrated that DEX-induced inhibition of Na v 1.8 currents was prevented by intracellular application of G-protein inhibitor GDPβ-s or G i/o  proteins inhibitor pertussis toxin (PTX), and bath application of adenylate cyclase (AC) activator forskolin or membrane-permeable cAMP analogue 8-Bromo-cAMP (8-Br-cAMP). PKA inhibitor Rp-cAMP could mimic DEX-induced inhibition of Na v 1.8 currents.    Conclusions  We established a functional link between α2-AR and Na v 1.8 in primary sensory neurons utilizing the G i/o /AC/cAMP/PKA pathway, which probably mediating peripheral analgesia of DEX.

Dexmedetomidine inhibits Tetrodotoxin-resistant Nav1.8 sodium channel activity through Gi/o-dependent pathway in rat dorsal root ganglion neurons