Literature Marathon

Pain modulation mechanisms 疼痛調整メカニズム   Some patients with neuropathic pain are moderately affected, whereas others experience debilitating pain. Moreover, patients show a large variability in response to distinct pharmacological (in terms of type and dose) and non-pharmacological treatments.   A key factor in this variability might be the way that the pain message is modulated in the CNS.   The pain signal can be augmented or reduced as it ascends from its entry port (the dorsal horn), relayed to the CNS and arrives at the cerebral cortex (the area crucial for consciousness). The various pathways and interference can, accordingly, modify the assumed correlation between the extent of the peripheral pathology and the extent of the pain syndrome. Most patients with neuropathic pain express a pro-nociceptive pain modulation profile — that is, pain messages are augmented in the CNS.   Thus, the perception of pain can be disinhibited ...

Management for Primary Frozen Shoulder Associated with Night Pain An Effect of Steroid Injection 夜間痛を伴う一次性肩関節拘縮に対する注射療法の効果 ( 河合ら .2011)   【本日のまとめ】 〇はじめに： ・ 夜間痛を伴う高度な肩関節拘縮 ( 挙上 ( 以下 AE)100 °以下、下垂位外旋 ( 以下 ER)10 °以下、結滞 ( 以下 IR) が L5 以下 ) に対する河合らの治療方針は、消炎処置として肩甲上腕関節にステロイド剤と局所麻酔の注射を夜間痛がほぼ消失するまで行う。その後理学療法を開始し満足いく治療成績が得られた。 ・本研究では炎症期として考えられる初診時に夜間痛を持った高度の一次性肩関節拘縮に対する、 消炎処置としてのステロイドの肩甲上腕関節内注射の効果 を検討。 〇対象： 初診時の AE100 °以下、 ER10 °以下、 IR が L5 以下の一次性肩関節拘縮 61 例 64 肩を対象とした。 ( 男性 21 例 21 肩、女性 40 例 43 肩、初診時平均年齢 58.9 歳、平均罹患期間 5.8 か月 ) 〇方法： 肩甲上腕関節内に Betamehasone4mg に 1% キシロカイン 4 ㎖ を混合した薬剤を注入。 〇結果： 平均 5(1-14) 回の関節内注射 (4.8 週間 ) で夜間痛消失 。 　 ROM( 平均° ) 　　初診時　 AE 88.2 　 ER 1.4 　 IR 仙骨レベル 　　夜間痛消失時　 AE 109.5 　 ER 12.9 　 IR L5     最終調査時　 AE 133.5   ER 12.9   IR L2   ※理学療法経過中 〇考察： ・滑膜炎が軽快し関節包の瘢痕形成が終止することで、関節可動域は改善され関節包のリモデリングが起こることが報告されている。 ・五十肩の初期 ( 炎症が強い早期 ) に肩甲上腕関節内にステロイド注射を施行することは滑膜炎の消...

  Areas such as the cingulate cortex and amygdala have been implicated in the ongoing pain state and comorbidities associated with neuropathic pain.   Projections from these forebrain areas modulate descending controls running from the periaqueductal grey (the primary control centre for descending pain modulation) to the brainstem and then act on spinal signalling. Indeed, numerous studies have shown that the brainstem excitatory pathways are more important in the maintenance of the pain state than in its induction.   ・大脳皮質と偏桃体といった部位は神経障害性疼痛に関連し生じている疼痛の状態や合併症に関与している。 ・これらの前脳領域からの投射は、中脳水道周囲灰白質（下行性の疼痛調節のための一次制御の中心）から脳幹まで続く下行制御を調節し、次いで脊髄シグナリングに作用する。 ・実際、多くの研究により脳幹の興奮性経路は疼痛が継続してしまっている場面でより重要な役割を果たしていることが分かっている     Noradrenergic inhibitions, mediated through α 2-adrenergic receptors in the spinal cord, are attenuated in neuropathic pain, and enhanced serotonin signalling through the 5-HT2 and 5-HT3 serotonin receptors bec...

Inhibitory modulation changes 抑制系調整機構の変化       In addition to changes in pain transmission neurons, inhibitory interneurons and descending modulatory control systems are dysfunctional in patients with neuropathic pain. Interneuron dysfunction contributes to the overall altered balance between descending inhibitions and excitations; specifically, neuropathy leads to a shift in excitation that now dominates. Consequently, the brain receives altered and abnormal sensory messages. Altered projections to the thalamus and cortex and parallel pathways to the limbic regions account for high pain ratings and anxiety, depression and sleep problems, which are relayed as painful messages that dominate limbic function.   ・疼痛の神経伝導の変化に加え、神経障害性疼痛患者において抑制性介在神経と下降性調整機構は機能不全に陥っている。 ・介在神経の機能不全は、下降性抑制と興奮とのバランスに全体的な変化をもたらす。 ・具体的には神経障害は興奮性に働きます。 ・その結果、脳が変化し異常となった感覚信号を受け取ることになる。 ・視床および皮質への変化した投射、ならびに辺縁領域への平行経路は、強い疼痛および不安、鬱病および睡眠の問題の説明を可能にし、これらは縁系機能を...

Neuropathic pain   PMC Luana Colloca, ら　 2017 Second-order nociceptive neuron alterations 二次侵害受容ニューロンの変化     Enhanced excitability of spinal neurons produces increased responses to many sensory modalities, enables low-threshold mechanosensitive A β and A δ afferent fibres to activate second-order nociceptive neurons (which convey sensory information to the brain) and expands their receptive fields so a given stimulus excites more second-order nociceptive neurons, generating the so-called central sensitization.     In particular, ongoing discharge of peripheral afferent fibres with concomitant release of excitatory amino acids and neuropeptides leads to postsynaptic changes in second-order nociceptive neurons, such as an excess of signalling due to phosphorylation of N-methyl-D-aspartate (NMDA) and α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.   These second-order changes plausibly e...

Neuropathic pain   PMC Luana Colloca, ら　 2017 Ion channel alterations イオンチャネルの変化   Neuropathy causes alterations in ion channels (sodium, calcium and potassium) within the affected nerves, which can include all types of afferent fibres that then affect spinal and brain sensory signaling.   For example, increased expression and function of sodium channels at the spinal cord terminus of the sensory nerves (mirrored by an enhanced expression of the α 2 δ subunit of calcium channels) lead to increased excitability, signal transduction and neurotransmitter release.   Indeed, the crucial role of sodium channels is shown by loss or gain of pain in humans with inherited channelopathies.   At the same time, a loss of potassium channels that normally modulate neural activity is also evident. If an afferent fibre is disconnected from the periphery due to an injury or a lesion, there will be sensory loss. However, the ...

Neuropathic pain   PMC Luana Colloca, ら　 2017   Pain signalling changes 疼痛シグナル伝導の変化   Peripheral neuropathy alters the electrical properties of sensory nerves, which then leads to imbalances between central excitatory and inhibitory signalling such that inhibitory interneurons and descending control systems are impaired.   ・末梢神経障害は感覚神経の電気的性質を変化させる。 ・中枢性興奮系シグナルと抑制系シグナル ( 抑制系介在ニューロンや下降性制御システムが障害されるように ) での不均等をもたらす。     In turn, transmission of sensory signals and disinhibition or facilitation mechanisms are altered at the level of the spinal cord dorsal horn neurons.   ・次に、①感覚信号の伝達、②メカニズムの脱抑制もしくは促進は、脊髄後角ニューロンのレベルで変化する。     Indeed, preclinical studies have revealed several anatomical, molecular and electrophysiological changes from the periphery through to the central nervous system (CNS) that produce a gain of function, providing insights into neuropathic pain and its treatment (BOX 4).  ...

Neuropathic pain   PMC Luana Colloca, ら　 2017        原因と分布 (Neuropathic pain8 からの続き )     The topography of the pain in these disorders typically encompasses the distal extremities, often called a ‘ glove and stocking ’ distribution because the feet, calves, hands and forearms are most prominently affected.   これらの疾患の疼痛は、遠位四肢に出現します。 この部位は足、ふくらはぎ、手、および前腕が最も顕著に影響を受けるため、一般的に「手袋とストッキング」と呼ばれる部位である。       This distribution pattern is characteristic of dying-back, length-dependent, distal peripheral neuropathies involving a distal-proximal progressive sensory loss, pain and, less frequently, distal weakness.   これらの疼痛部位は以下の特徴がある。 ①軸索変性 ( 近位に向かう変性 ) ②長さへの依存③遠位末梢神経障害 ( 遠位～近位の感覚麻痺、疼痛、多くはないが遠位部の低下 )     Less frequently, the pain has a proximal distribution in which the trunk, thighs and upper arms are particularly affected; this...

Neuropathic pain PMC Luana Colloca, ら　 2017         Neuropathic pain and diabetes mellitus 神経障害性疼痛と糖尿病   Painful chronic neuropathy in patients with diabetes mellitus ranges from 10% to 26%38. 糖尿病患者のうち痛みを伴う慢性の末梢神経障害の罹患率は 10~26% です。   Although risk factors and potential mechanisms underlying neuropathy have been studied extensively, the aetiology of the painful diabetic neuropathy is not completely known. 末梢神経障害に基づく危険因子と潜在的なメカニズムは広く研究されているが、糖尿病性の末梢神経障害性疼痛に関する病因は解明されていない。     However, findings from epidemiological studies have suggested that patients with diabetes mellitus who develop neuropathy, compared with those patients who do not, seem to have different cardiovascular function, glycaemic control, weight, rates of obesity, waist circumference, risk of peripheral arterial disease and triglyceride plasmid levels. しかし、疫学の研究によって 末梢神経症状を呈する糖尿病患者は症状がない患者と比較して以下のものに違いがあると思われる。 ( ...