Sodium Channel Blockers for the Treatment of Neuropathic Pain

Bhattacharya, Anindya; Wickenden, Alan D.; Chaplan, Sandra R.

doi:10.1016/j.nurt.2009.08.001

Cited by 60 publications

(32 citation statements)

References 200 publications

(143 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In support, functional knockdown of Na v 1.8 in rats or deletion of the Na v 1.8 gene reduces hyperalgesia and allodynia in neuropathic pain models (Dib-Hajj et al, 2010;Lampert et al, 2010). Likewise, systemic and spinal administrations of Na v 1.8 channel blockers partially reverse pain-related behaviors in preclinical animal models of chronic pain (Bear et al, 2009;Bhattacharya et al, 2009;Matulenko et al, 2009;Priest, 2009). Although Na v 1.8 antagonists may have analgesic efficacy in patients coping with chronic pain, the high degree of structural homology within the VGSC family and side effects of existing blockers have limited their clinical use (England, 2008;Dworkin et al, 2010).…”

Section: Discussionmentioning

confidence: 98%

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

Belkouch¹,

Dansereau²,

Goazigo³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

Changes in function of voltage-gated sodium channels in nociceptive primary sensory neurons participate in the development of peripheral hyperexcitability that occurs in neuropathic and inflammatory chronic pain conditions. Among them, the tetrodotoxin-resistant (TTX-R) sodium channel Na v 1.8, primarily expressed by small-and medium-sized dorsal root ganglion (DRG) neurons, substantially contributes to the upstroke of action potential in these neurons. Compelling evidence also revealed that the chemokine CCL2 plays a critical role in chronic pain facilitation via its binding to CCR2 receptors. In this study, we therefore investigated the effects of CCL2 on the density and kinetic properties of TTX-R Na v 1.8 currents in acutely small/medium dissociated lumbar DRG neurons from naive adult rats. Whole-cell patch-clamp recordings demonstrated that CCL2 concentration-dependently increased TTX-resistant Na v 1.8 current densities in both small-and medium-diameter sensory neurons. Incubation with CCL2 also shifted the activation and steady-state inactivation curves of Na v 1.

show abstract

Section: Discussionmentioning

confidence: 98%

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

Belkouch¹,

Dansereau²,

Goazigo³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Current analgesics include those that act locally (e.g., lidocaine) or attenuate neurotransmitter release through inhibition of ion channels (voltage-sensitive Ca 2+ , Na + , or K + channels) in central nerve pathways. Anticonvulsant and anesthetic sodium channel blockers have long been used to treat acute or chronic pain, such as trigeminal neuralgia, by reducing the generation of action potentials and nerve excitation (Bhattacharya et al, 2009). For peripheral pain, nonsteroidal anti-inflammatory drugs have mild 60 Veldhuis et al analgesic, anti-inflammatory, and antipyretic properties that inhibit production of algesic prostaglandins and are effective for inflammatory conditions such as arthritis (Andersson et al, 2011).…”

Section: A the Need For Alternative Therapeuticsmentioning

confidence: 99%

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

Veldhuis¹,

Poole²,

Grace³

et al. 2014

Pharmacol Rev

142

135

View full text Add to dashboard Cite

“…Both are central to human neuromuscular, cardiovascular, and neural physiology. Consequently, they are targets for a host of pharmaceuticals used to treat a diverse set of disorders and remain active targets for drug development (5)(6)(7). Recently, single subunit, six-transmembrane segment Na V s have been identified in a large number of bacteria from diverse environments (8,9).…”

mentioning

confidence: 99%

Voltage-gated sodium channel (Na_V) protein dissection creates a set of functional pore-only proteins

Shaya

Kreir

Robbins³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

133

View full text Add to dashboard Cite

Many voltage-gated ion channel (VGIC) superfamily members contain six-transmembrane segments in which the first four form a voltage-sensing domain (VSD) and the last two form the pore domain (PD). Studies of potassium channels from the VGIC superfamily together with identification of voltage-sensor only proteins have suggested that the VSD and the PD can fold independently. Whether such transmembrane modularity is common to other VGIC superfamily members has remained untested. Here we show, using protein dissection, that the Silicibacter pomeroyi voltagegated sodium channel (Na V Sp1) PD forms a stand-alone, ion selective pore (Na V Sp1p) that is tetrameric, α-helical, and that forms functional, sodium-selective channels when reconstituted into lipid bilayers. Mutation of the Na V Sp1p selectivity filter from LESWSM to LDDWSD, a change similar to that previously shown to alter ion selectivity of the bacterial sodium channel Na V Bh1 (NaChBac), creates a calcium-selective pore-only channel, Ca V Sp1p. We further show that production of PDs can be generalized by making pore-only proteins from two other extremophile Na V s: one from the hydrocarbon degrader Alcanivorax borkumensis (Na V Ab1p), and one from the arsenite oxidizer Alkalilimnicola ehrlichei (Na V Ae1p). Together, our data establish a family of active pore-only ion channels that should be excellent model systems for study of the factors that govern both sodium and calcium selectivity and permeability. Further, our findings suggest that similar dissection approaches may be applicable to a wide range of VGICs and, thus, serve as a means to simplify and accelerate biophysical, structural, and drug development efforts.V oltage-gated sodium channels (Na V s) are large polytopic membrane proteins involved in action potential generation in excitable cells and belong to an ion channel superfamily that includes voltage-gated calcium channels (Ca V s), voltage-gated potassium channels (K V s), and transient receptor potential (TRP) channels (1, 2). Within the voltage-gated ion channel (VGIC) superfamily, Na V s and Ca V s are close relatives (1-3) that share a topology of 24 transmembrane segments organized in four homologous six-transmembrane repeats. These two families are also thought to share some common structure in the ion selectivity filter despite having markedly different ion permeation properties (4). Both are central to human neuromuscular, cardiovascular, and neural physiology. Consequently, they are targets for a host of pharmaceuticals used to treat a diverse set of disorders and remain active targets for drug development (5-7). Recently, single subunit, six-transmembrane segment Na V s have been identified in a large number of bacteria from diverse environments (8, 9). These channels show clear similarities to eukaryotic Na V s and Ca V s (2, 9, 10), suggesting that the prokaryotic channels may have been ancestors of the more complex vertebrate channels.Despite the central importance of Na V s, nothing is known about the high-resolution structure o...

show abstract

Sodium Channel Blockers for the Treatment of Neuropathic Pain

Cited by 60 publications

References 200 publications

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

Voltage-gated sodium channel (Na_V) protein dissection creates a set of functional pore-only proteins

Contact Info

Product

Resources

About

Sodium Channel Blockers for the Treatment of Neuropathic Pain

Cited by 60 publications

References 200 publications

The Chemokine CCL2 Increases Nav1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The Chemokine CCL2 Increases Nav1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

Voltage-gated sodium channel (NaV) protein dissection creates a set of functional pore-only proteins

Contact Info

Product

Resources

About

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

The Chemokine CCL2 Increases Na_v1.8 Sodium Channel Activity in Primary Sensory Neurons through a Gβγ-Dependent Mechanism

Voltage-gated sodium channel (Na_V) protein dissection creates a set of functional pore-only proteins