機械的,冷たい,および炎症性疼痛の細胞および分子基礎
Bjarke Abrahamsen1, Jing Zhao, Curtis O Asante
1Molecular Nociception Group, University College London (UCL), Gower Street, London, WC1E 6BT, UK.
まとめ
ナトリウムチャネルNav1.8を表現する感覚神経は,機械的,冷たい,および炎症的な痛みを感知するために不可欠です. しかし,これらのニューロンは,熱感や神経疾患の痛みの発達に不可欠ではありません.
科学分野:
- 神経科学は神経科学である.
- 痛みの研究 痛みの研究
- 分子生物学は分子生物学である.
背景:
- 外部疼痛経路には,さまざまな刺激に反応する様々な感覚神経細胞が含まれています.
- ナトリウムチャネルNav1.8は,主に痛みのシグナル伝達に関与する特定の感覚ニューロンで発現します.
研究 の 目的:
- 異なるタイプの痛みの知覚におけるNav1.8発現感受ニューロンの特定の役割を調査する.
- Nav1.8を発現するニューロンが急性,炎症性,神経疾患性疼痛に欠かせないかどうかを判断する.
主な方法:
- ディフテリア毒素を用いて,Nav1.8.8を発現するマウスの転移後の感官ニューロンを選択的に排除した.
- 機械的,熱的,寒い刺激への反応として痛みの行動を評価した.
- 炎症的侮辱や神経損傷後の痛みの反応を評価した.
- 感覚ニューロンからの中央入力を測定し,in vivoで電気生理学的に測定する.
主要な成果:
- Nav1.8発現ニューロンを欠いたマウスは,正常な運動機能と急性熱に対する反応を示したが,有害な機械的圧力と寒さに反応しなかった.
- これらのマウスは,炎症的な侮辱の後,痛みが解消され,痛みが強化され,自発的な痛みの行動を示しました.
- 神経損傷は,コントロールの littermatesに類似して,これらのマウスの痛みの感受性を高めました.
- 電気生理学的記録は,痛みの行動と中央感覚神経細胞の入力との関連性を確認しました.
結論:
- Nav1.8を発現する感覚ニューロンは,機械的,冷たい,炎症的な痛みの感覚に不可欠です.
- これらのニューロンは,急性有害な熱を感知したり,神経疾患の痛みを発症させるのに必要ありません.
- 発見は, Nav1.8 チャンネルが異なる痛み様式に与える特定の貢献を強調しています.
関連する概念動画
Nociception
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain. Thus, pain helps the...
Thermosensation
Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
Pain
Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
Acute Inflammation III: Local and Systemic Effects
Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...


