Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator

Jiang, Feng; Hua, Liming; Jiao, Yun-Lu; Pin, Ye; Fu, Jin; Cheng, Zhiwei; Ding, Gang; Ji, Yonghua

doi:10.1007/s12264-013-1377-0

Cited by 16 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We postulate that the up-regulation of Nav1.8 in peripheral nervous system may drive these signalings in spinal cord. In DRG neurons, we also found that several intracellular signal pathways are activated, including p38 and mTOR, which are in parallel with the up-regulation of Nav1.8 [30,31]. It is possible that the mTOR and p38 signaling pathways may be involved in the alteration of Nav1.8 expression and function in DRG neurons in 2 h. However, the exact roles of these signaling pathways in the regulation of Nav1.8 expression are unclear and require further investigation.…”

Section: Discussionmentioning

confidence: 80%

“…However, Wood et al [44] found that Nav1.8-null mice exhibited an increased acute pain threshold to noxious mechanical stimuli, but not thermal stimuli, applied to the neuronal peripheral receptive field. Nav1.8 AS-ODNs or ambroxol (a Nav1.8 blocker) administrated to the spinal cord in rats reduced the mechanical hypersensitivity induced by CFA [35,42], but was not effective in the mechanical and thermal hypersensitivity induced by melittin [30]. A-803467, a selective Nav1.8 blocker, dose-dependently reduces mechanical allodynia in a variety of rat inflammation pain models, including capsaicin-induced secondary mechanical allodynia and thermal hyperalgesia after intraplantar CFA injection, but is inactive against formalin-induced nociception and acute thermal and postoperative pain [27].…”

Section: Discussionmentioning

confidence: 99%

“…Western blot analysis was performed according to the previous reports [30,31]. Briefly, after the BmK I injection at different time points (2 h, 8 h, and 1 day), the rats were anesthetized with intraperitoneal (i.p.)…”

Section: Western Blot Analysismentioning

confidence: 99%

See 2 more Smart Citations

Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain

Hua

Jiao

et al. 2016

ABBS

Self Cite

View full text Add to dashboard Cite

BmK I, purified from the venom of scorpion Buthus martensi Karsch (BmK), is a receptor site-3-specific modulator of voltage-gated sodium channels (VGSCs) and can induce pain-related behaviors in rats. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 contributes to most of the sodium current underlying the action potential upstroke in dorsal root ganglia (DRG) neurons and may serve as a critical ion channel targeted by BmK I. Herein, using electrophysiological, molecular, and behavioral approaches, we investigated whether the aberrant expression of Nav1.8 in DRG contributes to generation of pain induced by BmK I. The expression of Nav1.8 was found to be significantly increased at both mRNA and protein levels following intraplantar injection of BmK I in rats. In addition, the current density of TTX-R Nav1.8 sodium channel is significantly increased and the gating kinetics of Nav1.8 is also altered in DRG neurons from BmK I-treated rats. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, are significantly alleviated through either blockade of the Nav1.8 sodium channel by its selective blocker A-803467 or knockdown of the Nav1.8 expression in DRG by antisense oligodeoxynucleotide (AS-ODN) targeting Nav1.8 in rats. Finally, BmK I was shown to induce enhanced pain behaviors in complete freund's adjuvant (CFA)-inflamed rats, which was partly due to the over-expression of Nav1.8 in DRG. Our results suggest that functional up-regulation of Nav1.8 channel on DRG neurons contributes to the development of BmK I-induced pain in rats.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain

Hua

Jiao

et al. 2016

ABBS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Неоваскуляризация, обусловленная высокой экспресси-ей СЭФР, также может приводить к усилению боли, по-скольку образование новых сосудов сопровождается фор-мированием сенсорных нейронов [39]. Кроме того, появ-ление боли у этих пациентов может способствовать ВЭ ге-на mTOR, которую также связывают с формированием бо-ли [29,30].…”

Section: Discussionunclassified

“…Поскольку на молекулярном уровне боль ассоции-руется с экспрессией генов, участвующих в развитии вос-паления и разрушении ВКМ, она тесно связана с нару-шениями основных метаболических путей, и прежде все-го -регулируемых mTOR (Mammalian Target Of Rapamycin), который является главным регулятором цен-тральной и периферической болевой чувствительности [29,30]. Усиление боли отмечается как при повышенной, так и при пониженной экспрессии mTOR [17,31].…”

unclassified