Modulation of Nav1.8 by Lysophosphatidic Acid in the Induction of Bone Cancer Pain

Abstract

Given that lysophosphatidic acid (LPA) and the tetrodotoxin-resistant sodium channel Na v 1.8 are both involved in bone cancer pain, the present study was designed to investigate whether crosstalk between the LPA receptor LPA 1 (also known as EDG2) and Na v 1.8 in the dorsal root ganglion (DRG) contributes to the induction of bone cancer pain. We showed that the EDG2 antagonist Ki16198 blocked the mechanical allodynia induced by intrathecal LPA in naïve rats and attenuated mechanical allodynia in a rat model of bone cancer. EDG2 and Na v 1.8 expression in L 4-6 DRGs was upregulated following intrathecal or hindpaw injection of LPA. EDG2 and Na v 1.8 expression in ipsilateral L 4-6 DRGs increased with the development of bone cancer. Furthermore, we showed that EDG2 co-localized with Na v 1.8 and LPA remarkably enhanced Na v 1.8 currents in DRG neurons, and this was blocked by either a protein kinase C (PKC) inhibitor or a PKCe inhibitor. Overall, we demonstrated the modulation of Na v 1.8 by LPA in DRG neurons, and that this probably underlies the peripheral mechanism by which bone cancer pain is induced.

α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

“…Moreover, the sodium current density and the expression of NaV1.7 and NaV1.8 were remarkably enhanced in colon DRGs of rats with diabetes,15 indicating that both NaV1.7 and NaV1.8 play an important role in generation of diabetic colon hypersensitivity. This is consistent with previous reports that both NaV1.7 and NaV1.8 are involved in chronic pain conditions 38,39. Since ALA attenuated the colonic visceral hypersensitivity, it is reasonable to hypothesize that ALA treatment attenuated the colonic visceral hypersensitivity through suppressing NaV1.7 and NaV1.8 expressions and sodium current density in colon DRG neurons of rats with diabetes.…”

Overexpression of suppressor of cytokine signaling 3 in dorsal root ganglion attenuates cancer-induced pain in rats

“…The procedures for induction of BC pain model were in accordance with the previous report. 25 , 26 In brief, rats were anesthetized with Chloral hydrate (360 mg/kg, i.p.) for surgery.…”

Recent Progress in Understanding the Mechanisms of Pain and Itch: the Second Special Issue

“…In the last 5 years, the field has seen tremendous progress in the molecular and functional characterization of primary sensory neurons [6,7], neurocircuits of pain and itch [8][9][10], immune and glial modulation of pain and itch [11][12][13][14][15], molecular mechanisms of pain [16,17], and identification of brain signatures of pain [18]. Thus, it is timely to highlight the recent progress in a second special issue.…”

“…For example, the TTX-resistant Na ? channel subunit Nav1.8 contributes to the development of bone cancer pain in rodents [16]. To enhance the translational potential of preclinical studies, Chang et al compared the expression of TTX-sensitive and TTX-resistant Na ?…”