皮質の痛み回路におけるオピオイド鎮痛を模倣する

Corinna S Oswell^1,2,3, Sophie A Rogers^1,2,3, Justin G James^1,4,5

¹Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Nature

|January 7, 2026

まとめ

モルヒネは,慢性的な痛みに関係している特定の脳回路を標的にする

科学分野:

神経科学
薬理学について
遺伝学

背景:

前帯状皮質 (ACC) は痛みの感情的な側面に不可欠です
オピオイドが痛みを和らげるためにACC回路にどのように影響するかは完全に理解されていません.
これらの回路をターゲットにすることが慢性疼痛の治療法の開発の鍵です

研究の目的:

慢性疼痛における ACC 神経活動にモルヒンがどのように作用するかを調べるため
痛みの行動に関与する ACC の特定のニューロン集団を特定するために
痛みを治療するための新しい遺伝子治療法を開発する

主な方法:

マウスにおけるディープラーニングの行動分析
ネズミの長距離神経記録です
オピオイドに敏感なACCニューロンを標的とした化学遺伝療法の開発

主要な成果:

ACCニューロンの特定の集団は痛みの行動をコードしモルヒネによって調節されます
神経損傷はACCの活動に持続的な変化を引き起こし,感情的な痛み状態を反映した.
モルフィンは神経の変化を逆転させ感覚の検出に影響を及ぼさずに痛みを軽減しました
開発された化学遺伝療法は慢性的な痛みに対するモルフィンの鎮痛効果を模倣したものです

結論:

オピオイド鎮痛剤は慢性的な痛みの感情的な側面に関与するACC回路を選択的に調節します
これらのオピオイドに敏感なACCニューロンをターゲットにすることで痛みの精密な管理に有望な戦略が生まれます
化学遺伝子治療はオピオイドの作用を模倣して安全なオンデマンドのアプローチで痛みを軽減します

さらに関連する動画

07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

34.0K

10:39

3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache

Published on: June 2, 2014

18.7K

関連する概念動画

01:25

Analgesia and Pain Management

1.5K

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...

1.5K

01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

906

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...

906

01:20

Pain

1.2K

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...

1.2K

01:22

Opioid Receptors: Overview

4.0K

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...

4.0K

01:20

Opioid Analgesics: Morphine and Other Natural Cogeners

841

Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...

841

01:44

Nociception

33.0K

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.