Last update 01 Nov 2024

Nav1.8 x ASIC3

Last update 01 Nov 2024

Basic Info

Related Targets

Nav1.8ASIC3

Drugs associated with Nav1.8 x ASIC3

TH-902

Target

ASIC3 x Nav1.8

Mechanism

ASIC3 inhibitors [+1]

Active Org.-

Originator Org.

Theralpha S.A.S.

Active Indication-

Inactive Indication

Fibromyalgia [+2]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Nav1.8 x ASIC3

100 Translational Medicine associated with Nav1.8 x ASIC3

0 Patents (Medical) associated with Nav1.8 x ASIC3

Literatures (Medical) associated with Nav1.8 x ASIC3

01 Apr 2024·Inflammation Research

Complex alterations in inflammatory pain and analgesic sensitivity in young and ageing female rats: involvement of ASIC3 and Nav1.8 in primary sensory neurons

Article

Author: Peralta, Emanuel D ; Acosta, Cristian G ; Messina, Diego N

OBJECTIVE AND DESIGNOur aim was to determine an age-dependent role of Nav1.8 and ASIC3 in dorsal root ganglion (DRG) neurons in a rat pre-clinical model of long-term inflammatory pain.METHODSWe compared 6 and 24 months-old female Wistar rats after cutaneous inflammation. We used behavioral pain assessments over time, qPCR, quantitative immunohistochemistry, selective pharmacological manipulation, ELISA and in vitro treatment with cytokines.RESULTSOlder rats exhibited delayed recovery from mechanical allodynia and earlier onset of spontaneous pain than younger rats after inflammation. Moreover, the expression patterns of Nav1.8 and ASIC3 were time and age-dependent and ASIC3 levels remained elevated only in aged rats. In vivo, selective blockade of Nav1.8 with A803467 or of ASIC3 with APETx2 alleviated mechanical and cold allodynia and also spontaneous pain in both age groups with slightly different potency. Furthermore, in vitro IL-1β up-regulated Nav1.8 expression in DRG neurons cultured from young but not old rats. We also found that while TNF-α up-regulated ASIC3 expression in both age groups, IL-6 and IL-1β had this effect only on young and aged neurons, respectively.CONCLUSIONInflammation-associated mechanical allodynia and spontaneous pain in the elderly can be more effectively treated by inhibiting ASIC3 than Nav1.8.

01 Apr 2023·Indian Journal of Ophthalmology

Ion channels in dry eye disease

Review

Author: Khamar, Pooja ; Gijs, Marlies ; Ghosh, Arkasubhra ; Ashok, Nikhil ; Sethu, Swaminathan ; D’Souza, Sharon ; Shetty, Rohit

Dry eye disease (DED) which affects millions of people worldwide is an ocular surface disease that is strongly associated with pain, discomfort, and visual disturbances. Altered tear film dynamics, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities are the key contributors to DED pathogenesis. The presence of discordance between signs and symptoms of DED in patients and refractoriness to current therapies in some patients underpin the need for studying additional contributors that can be modulated. The presence of electrolytes or ions including sodium, potassium, chloride, bicarbonate, calcium, and magnesium in the tear fluid and ocular surface cells contribute to ocular surface homeostasis. Ionic or electrolyte imbalance and osmotic imbalance have been observed in DED and feed-forward interaction between ionic imbalances and inflammation alter cellular processes in the ocular surface resulting in DED. Ionic balances in various cellular and intercellular compartments are maintained by dynamic transport via ion channel proteins present in cell membranes. Hence, alterations in the expression and/or activity of about 33 types of ion channels that belong to voltage-gated channels, ligand-gated channels, mechanosensitive ion channel, aquaporins, chloride ion channel, sodium–potassium–chloride pumps or cotransporters have been investigated in the context of ocular surface health and DED in animal and/or human subjects. An increase in the expression or activity of TRPA1, TRPV1, Nav1.8, KCNJ6, ASIC1, ASIC3, P2X, P2Y, and NMDA receptor have been implicated in DED pathogenesis, whereas an increase in the expression or activity of TRPM8, GABAA receptor, CFTR, and NKA have been associated with resolution of DED.

01 Feb 2023·Biogerontology

Age-dependent and modality-specific changes in the phenotypic markers Nav1.8, ASIC3, P2X3 and TRPM8 in male rat primary sensory neurons during healthy aging

Article

Author: Seltzer, Alicia M ; Peralta, Emanuel D ; Patterson, Sean I ; Acosta, Cristian G ; Messina, Diego N

The effects during healthy aging of the tetrodotoxin-resistant voltage-gated sodium channel 1.8 (Nav1.8), the acid-sensing ion channel-3 (ASIC3), the purinergic-receptor 2X3 (P2X3) and transient receptor potential of melastatin-8 (TRPM8) on responses to non-noxious stimuli are poorly understood. These effects will influence the transferability to geriatric subjects of findings obtained using young animals. To evaluate the involvement of these functional markers in mechanical and cold sensitivity to non-noxious stimuli and their underlying mechanisms, we used a combination of immunohistochemistry and quantitation of immunostaining in sub-populations of neurons of the dorsal root ganglia (DRG), behavioral tests, pharmacological interventions and Western-blot in healthy male Wistar rats from 3 to 24 months of age. We found significantly decreased sensitivity to mechanical and cold stimuli in geriatric rats. These behavioural alterations occurred simultaneously with differing changes in the expression of Nav1.8, ASIC3, P2X3 and TRPM8 in the DRG at different ages. Using pharmacological blockade in vivo we demonstrated the involvement of ASIC3 and P2X3 in normal mechanosensation and of Nav1.8 and ASIC3 in cold sensitivity. Geriatric rats also exhibited reductions in the number of A-like large neurons and in the proportion of peptidergic to non-peptidergic neurons. The changes in normal sensory physiology in geriatric rats we report here strongly support the inclusion of aged rodents as an important group in the design of pre-clinical studies evaluating pain treatments.

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