There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Nociception is essential for survival whereas pathological pain is maladaptive and often unresponsive to pharmacotherapy. Voltage-gated sodium channels, Na(v)1.1-Na(v)1.9, are essential for generation and conduction of electrical impulses in excitable cells. Human and animal studies have identified several channels as pivotal for signal transmission along the pain axis, including Na(v)1.3, Na(v)1.7, Na(v)1.8, and Na(v)1.9, with the latter three preferentially expressed in peripheral sensory neurons and Na(v)1.3 being upregulated along pain-signaling pathways after nervous system injuries. Na(v)1.7 is of special interest because it has been linked to a spectrum of inherited human pain disorders. Here we review the contribution of these sodium channel isoforms to pain.

Related collections

Most cited references 124

Record: found
Abstract: found
Article: not found

Nociceptors are interleukin-1beta sensors.

Alexander Binshtok, Haibin Wang, Katharina Zimmermann … (2008)

A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E(2), bradykinin, and nerve growth factor, that reduce the threshold and increase the excitability of the peripheral terminals of nociceptors so that they now respond to innocuous stimuli: the phenomenon of peripheral sensitization. We show here that the proinflammatory cytokine interleukin-1beta (IL-1beta), in addition to producing inflammation and inducing synthesis of several nociceptor sensitizers, also rapidly and directly activates nociceptors to generate action potentials and induce pain hypersensitivity. IL-1beta acts in a p38 mitogen-activated protein kinase (p38 MAP kinase)-dependent manner, to increase the excitability of nociceptors by relieving resting slow inactivation of tetrodotoxin-resistant voltage-gated sodium channels and also enhances persistent TTX-resistant current near threshold. By acting as an IL-1beta sensor, nociceptors can directly signal the presence of ongoing tissue inflammation.

0 comments Cited 229 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.

A Akopian, L Sivilotti, J Wood (1996)

Dorsal root ganglion sensory neurons associated with C-fibres, many of which are activated by tissue-damage, express an unusual voltage-gated sodium channel that is resistant to tetrodotoxin. We report here that we have identified a 1,957 amino-acid sodium channel in these cells that shows 65% identity with the rat cardiac tetrodotoxin-insensitive sodium channel, and is not expressed in other peripheral and central neurons, glia or non-neuronal tissues. In situ hybridization shows that the channel is expressed only by small-diameter sensory neurons in neonatal and adult dorsal root and trigeminal ganglia. The channel is resistant to tetrodotoxin when expressed in Xenopus oocytes. The electrophysiological and pharmacological properties of the expressed channel are similar to those described for the small-diameter sensory neuron tetrodotoxin-resistant sodium channels. As some noxious input into the spinal cord is resistant to tetrodotoxin, block of expression or function of such a C-fibre-restricted sodium channel may have a selective analgesic effect.

0 comments Cited 176 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The cell and molecular basis of mechanical, cold, and inflammatory pain.

Curtis O. Asante, Cruz Cendán, Jing-Ping Zhao … (2008)

Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Na(v)1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.

0 comments Cited 161 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

PubMed ID:: 20367448

DOI:: 10.1146/annurev-neuro-060909-153234

ScienceOpen disciplines: Chemistry

Keywords: Animals,Disease Models, Animal,Genetic Predisposition to Disease,genetics,Humans,Nociceptors,metabolism,Pain,physiopathology,Sensory Receptor Cells,Sodium Channels

Data availability:

ScienceOpen disciplines: Chemistry

Keywords: Animals, Disease Models, Animal, Genetic Predisposition to Disease, genetics, Humans, Nociceptors, metabolism, Pain, physiopathology, Sensory Receptor Cells, Sodium Channels

Sodium channels in normal and pathological pain.

Read this article at

Abstract

Related collections

Annual Reviews - curated articles

Most cited references 124

Nociceptors are interleukin-1beta sensors.

A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.

The cell and molecular basis of mechanical, cold, and inflammatory pain.

Author and article information

Journal

Comments

Comment on this article

Similar content 51

Cited by 186

Most referenced authors 1,382