Choosing medication for painful diabetic neuropathy is not only about pain reduction. Tolerability and staying on treatment matter just as much. 有痛性糖尿病性ニューロパチーの薬剤選択では、効果だけでなく、副作用や継続しやすさも重要です。 Source Quilici S, Chancellor J, Löthgren M, Simon D, Said G, Le TK, Garcia-Cebrian A, Monz B. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. BMC Neurol. 2009 Feb 10;9:6. PMID: 19208243; PMCID: PMC2663537. https://pubmed.ncbi.nlm.nih.gov/19208243/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

How should we choose between duloxetine, pregabalin, and gabapentin for painful diabetic peripheral neuropathy? In this video, Dr. Akihiro Ando reviews a 2009 meta-analysis published in BMC Neurology that examined indirect comparisons among duloxetine, pregabalin, and gabapentin for diabetic peripheral neuropathic pain (DPNP). Because direct head-to-head trials were limited, the authors compared these medications through placebo-controlled trial data to explore differences in efficacy and tolerability. The paper suggests that all three medications showed benefit over placebo for painful diabetic neuropathy. In the indirect comparison, duloxetine appeared broadly comparable to pregabalin and gabapentin for overall pain reduction, although pregabalin was favored on patient global impression outcomes and duloxetine was favored on dizziness. The study also highlights an essential clinical reality: treatment choice is not only about pain relief, but also about adverse effects, discontinuation, comorbidities, and whether a patient can remain on therapy long enough to benefit. This review also discusses the important limitations of indirect meta-analysis, including small study numbers, limited gabapentin data, differences across trial populations, and the fact that indirect comparisons are not a substitute for true head-to-head randomized trials. This is a practical paper for clinicians managing neuropathic pain, because it supports multiple evidence-based options rather than a single “best” drug. 有痛性糖尿病性末梢神経障害に対して、duloxetine、pregabalin、gabapentinのどれを選ぶべきでしょうか。 この動画では、Dr. Akihiro Andoが、BMC Neurology に2009年に掲載されたメタアナリシスをもとに、糖尿病性末梢神経障害性疼痛（DPNP）に対する duloxetine、pregabalin、gabapentin の比較を解説します。直接比較試験が限られている中で、この論文はプラセボ対照試験を共通比較対象として用いた間接比較により、有効性と忍容性を検討しています。 論文の結果からは、3剤はいずれもプラセボより疼痛改善効果を示しました。間接比較では、主な疼痛アウトカムにおいて duloxetine は pregabalin や gabapentin と概ね同等と考えられました。一方で、患者全体評価では pregabalin がやや有利であり、めまいに関しては duloxetine が有利でした。つまり、薬剤選択は単純に「どれが一番効くか」ではなく、副作用、治療中止率、併存症、継続しやすさなどを含めて考える必要があることを示しています。 またこのレビューでは、間接メタアナリシスの限界についても詳しく取り上げます。特に、対象試験数の少なさ、gabapentin に関するデータの限界、試験間の患者背景の違い、そして間接比較は真の直接比較試験を置き換えるものではないという点は重要です。 臨床的には、「唯一の勝者」を決める論文というより、複数の妥当な治療選択肢をどう患者ごとに使い分けるかを考えるうえで参考になる論文です。 Source Quilici S, Chancellor J, Löthgren M, Simon D, Said G, Le TK, Garcia-Cebrian A, Monz B. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. BMC Neurol. 2009 Feb 10;9:6. PMID: 19208243; PMCID: PMC2663537. https://pubmed.ncbi.nlm.nih.gov/19208243/ #糖尿病性神経障害 #神経障害性疼痛 #デュロキセチン #プレガバリン #ガバペンチン #痛み治療 #EBM #DiabeticNeuropathy #NeuropathicPain #Duloxetine #Pregabalin #Gabapentin #PainManagement #EvidenceBasedMedicine ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

This paper frames neuropathic pain as more than excess nociceptive input—it may also reflect impaired endogenous inhibition. 神経障害性疼痛は入力の増加だけでなく、内因性の抑制機構がうまく働かない状態としても捉えられます。 Source Giancotti LA, Squillace S, Chen Z, Lauro F, Li Y, Salvemini D. Ozanimod, a functional sphingosine-1-phosphate receptor 1 antagonist, restores brainstem descending pain pathways in murine models of neuropathic pain. Pain. 2025 Nov 1;166(11):2510-2518. PMID: 40758546. https://pubmed.ncbi.nlm.nih.gov/40758546/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

In rodent models of traumatic and chemotherapy-induced neuropathic pain, systemic ozanimod showed broad antinociceptive effects. 外傷性神経障害性疼痛と化学療法誘発性ニューロパチーのモデルで、ozanimodは広い鎮痛効果を示しました。 Source Giancotti LA, Squillace S, Chen Z, Lauro F, Li Y, Salvemini D. Ozanimod, a functional sphingosine-1-phosphate receptor 1 antagonist, restores brainstem descending pain pathways in murine models of neuropathic pain. Pain. 2025 Nov 1;166(11):2510-2518. PMID: 40758546. https://pubmed.ncbi.nlm.nih.gov/40758546/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

A multiple sclerosis drug may offer a new way to think about neuropathic pain: not just peripheral nerve damage, but failed top-down pain control. 神経障害性疼痛は末梢神経だけの問題ではなく、脳からの抑制系の破綻も関係している可能性があります。 Source Giancotti LA, Squillace S, Chen Z, Lauro F, Li Y, Salvemini D. Ozanimod, a functional sphingosine-1-phosphate receptor 1 antagonist, restores brainstem descending pain pathways in murine models of neuropathic pain. Pain. 2025 Nov 1;166(11):2510-2518. PMID: 40758546. https://pubmed.ncbi.nlm.nih.gov/40758546/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

Can an FDA-approved multiple sclerosis drug help restore dysfunctional descending pain control in neuropathic pain? In this video, I review a 2025 paper published in *PAIN* examining ozanimod, an S1PR1 modulator, in rodent models of neuropathic pain. The study suggests that ozanimod not only reduces pain-like hypersensitivity across traumatic and chemotherapy-induced neuropathy models, but may also act within the rostral ventral medulla (RVM), a key brainstem region involved in descending pain modulation. A particularly interesting aspect of this paper is the mechanistic focus on supraspinal pain control. The authors provide evidence that S1PR1 signaling in the RVM contributes to maintenance of neuropathic pain, and that ozanimod may help re-engage descending inhibitory pathways involving serotonergic and noradrenergic signaling at the spinal level. They also report normalization of type I interferon-related gene expression in the RVM, adding an important mechanistic hypothesis. This matters clinically because neuropathic pain is often framed mainly as a peripheral nerve or spinal cord problem. This study reminds us that impaired top-down inhibitory control may also be part of the disease state. At the same time, this remains a preclinical animal study, so the findings should be interpreted cautiously until human data are available. In this review, I discuss: - why the RVM is important in neuropathic pain - how ozanimod performed in multiple rodent models - what the RNA-seq findings may mean mechanistically - the strengths and limitations of the paper - what this study may imply for future translational pain research FDA承認済みの多発性硬化症治療薬が、神経障害性疼痛における下降性疼痛抑制の破綻を改善する可能性はあるのでしょうか。 この動画では、2025年に *PAIN* に掲載された論文をもとに、S1PR1モジュレーターであるozanimodが神経障害性疼痛モデルに与える影響をレビューします。本研究では、ozanimodが外傷性神経障害モデルおよび化学療法誘発性ニューロパチーモデルにおいて痛覚過敏を軽減するだけでなく、脳幹の重要な疼痛調節部位であるrostral ventral medulla（RVM）に作用し、下降性抑制系を再活性化する可能性が示されています。 特に興味深いのは、この論文が脊髄上位の疼痛制御機構に焦点を当てている点です。著者らは、RVMにおけるS1PR1シグナルが神経障害性疼痛の維持に関与し、ozanimodが脊髄レベルのセロトニン系およびノルアドレナリン系の下降性抑制回路を介して鎮痛効果を発揮する可能性を示しました。さらに、RVM内のI型インターフェロン関連遺伝子発現の正常化も報告しており、機序的にも非常に示唆に富む内容です。 臨床的に重要なのは、神経障害性疼痛を末梢神経や脊髄だけの問題として捉えるのではなく、トップダウンの抑制制御の破綻を含むネットワーク異常として考える視点を与えてくれることです。ただし、本研究は前臨床の動物実験であり、ヒトにおける有効性が示されたわけではないため、解釈には慎重さが必要です。 このレビューでは、以下の点を解説します。 - 神経障害性疼痛におけるRVMの役割 - 複数の動物モデルでみたozanimodの効果 - RNA-seqの所見が示唆する機序 - この研究の強みと限界 - 今後のトランスレーショナル研究への意義 Source Giancotti LA, Squillace S, Chen Z, Lauro F, Li Y, Salvemini D. Ozanimod, a functional sphingosine-1-phosphate receptor 1 antagonist, restores brainstem descending pain pathways in murine models of neuropathic pain. Pain. 2025 Nov 1;166(11):2510-2518. PMID: 40758546. https://pubmed.ncbi.nlm.nih.gov/40758546/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

The animal data are encouraging, but this review does not yet support routine supplementation protocols for patients after peripheral nerve injury. 動物研究では有望な結果が示されていますが、末梢神経損傷後の患者さんに routine でサプリメントを使う根拠としては、まだ不十分です。 Source Abushukur Y, Knackstedt R. The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature. Cureus. 2022 May 19;14(5):e25135. PMID: 35733475; PMCID: PMC9205410. http://pubmed.ncbi.nlm.nih.gov/35733475/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

Among the supplements reviewed, alpha-lipoic acid showed fairly consistent preclinical support for antioxidant effects and nerve recovery outcomes. αリポ酸は、今回のレビューで比較的一貫した前臨床データが示されたサプリメントの一つです。ただし、臨床応用にはさらなる研究が必要です。 Source Abushukur Y, Knackstedt R. The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature. Cureus. 2022 May 19;14(5):e25135. PMID: 35733475; PMCID: PMC9205410. http://pubmed.ncbi.nlm.nih.gov/35733475/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

A promising concept, but still early evidence. This review suggests some supplements may support peripheral nerve regeneration, mainly based on animal studies. 末梢神経損傷後の回復にサプリメントは役立つのか。可能性はありますが、現時点では主に動物研究に基づく予備的な知見です。 Source Abushukur Y, Knackstedt R. The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature. Cureus. 2022 May 19;14(5):e25135. PMID: 35733475; PMCID: PMC9205410. http://pubmed.ncbi.nlm.nih.gov/35733475/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

Can supplements improve recovery after peripheral nerve injury? In this video, I review the literature on nutritional supplements and nerve regeneration, based on the paper “The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature.” This review covers a range of agents with antioxidant, anti-inflammatory, or neuroprotective properties, including melatonin, curcumin, alpha-lipoic acid, citicoline, vitamin B12, and vitamin E. Across animal studies, these supplements were associated with improvements in outcomes such as axonal regeneration, myelination, conduction velocity, functional recovery, and oxidative stress markers. At the same time, the key clinical point is caution. Most of the evidence summarized in this review comes from preclinical animal models rather than human trials. That means the biological rationale is promising, but the evidence is not yet strong enough to support routine clinical supplementation protocols for patients with peripheral nerve injury. In this discussion, I focus on what the paper actually supports, which supplements appear most promising preclinically, and why better prospective human studies are still needed before changing practice. This video is intended for educational purposes and should not be taken as personal medical advice. 末梢神経損傷後の回復に、サプリメントは役立つのでしょうか。この動画では、「The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature」というレビュー論文をもとに、栄養補助食品と神経再生に関するエビデンスを整理して解説します。 本レビューでは、メラトニン、クルクミン、α-リポ酸、シチコリン、ビタミンB12、ビタミンEなど、抗酸化作用・抗炎症作用・神経保護作用が期待される成分が取り上げられています。動物実験では、軸索再生、髄鞘化、神経伝導、機能回復、酸化ストレス指標の改善など、前向きな所見が報告されています。 一方で、臨床的に最も重要なのは慎重な解釈です。このレビューで示されている根拠の大半はヒトではなく前臨床の動物研究に基づいています。そのため、メカニズムはもっともらしく、動物データも有望ではあるものの、現時点で末梢神経損傷患者に対する routine のサプリメント投与を支持するには十分とはいえません。 この動画では、論文が実際に何を示しているのか、どのサプリメントが前臨床的に有望なのか、そしてなぜ今後のヒト前向き試験が必要なのかを、臨床的な視点からバランスよく解説します。 本動画は教育目的であり、個別の医学的助言を行うものではありません。 Source Abushukur Y, Knackstedt R. The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature. Cureus. 2022 May 19;14(5):e25135. PMID: 35733475; PMCID: PMC9205410. http://pubmed.ncbi.nlm.nih.gov/35733475/ ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

Paroxysmal hemicrania is classically indomethacin-responsive, but real-world treatment is not always simple. Side effects are common, and many patients go through unnecessary procedures before the correct diagnosis is made. 発作性片側頭痛はインドメタシン反応性が特徴ですが、実臨床では治療はそれほど単純ではありません。副作用も多く、正しい診断に至る前に不要な処置を受けている患者も少なくありません。 Source Al-Taee A, Botros J, Groenke BR, Nixdorf DR. Paroxysmal hemicrania: A diagnostic challenge presenting as orofacial pain: A case series. Cranio. 2025 Dec 28:1-8. PMID: 41456204. https://pubmed.ncbi.nlm.nih.gov/41456204/ #Indomethacin #ParoxysmalHemicrania #OrofacialPain #Misdiagnosis #DentalProcedures #FacialPain #PainMedicine #MedicalShorts ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical

When severe unilateral facial or dental pain comes with tearing, redness, rhinorrhea, or swelling on the same side, the diagnosis may extend beyond dental disease or TMD. That pattern should immediately broaden the differential. 強い片側性の顔面痛や歯痛に、流涙、発赤、鼻汁、腫脹などの同側の自律神経症状を伴う場合、診断は歯科疾患やTMDだけではありません。そのパターンは鑑別診断を大きく広げる重要な手がかりです。 Source Al-Taee A, Botros J, Groenke BR, Nixdorf DR. Paroxysmal hemicrania: A diagnostic challenge presenting as orofacial pain: A case series. Cranio. 2025 Dec 28:1-8. PMID: 41456204. https://pubmed.ncbi.nlm.nih.gov/41456204/ #FacialPain #AutonomicSymptoms #ParoxysmalHemicrania #TMD #DentalDiagnosis #OrofacialPain #TrigeminalAutonomicCephalalgia #ClinicalClues ⸻ Websites Akihiro Ando Portal: https://www.akihiroando.com Ando Orofacial Pain & Oral Medicine Clinic: https://www.ando-pain.jp TED Talk: https://www.ted.com/talks/akihiro_ando_this_thing_called_pain ⸻ Facebook Spark Medical: https://www.facebook.com/sparkmeds/ Ando Orofacial Pain & Oral Medicine: https://www.facebook.com/andoofpom/ Spark Medical Presentation Workshop: https://www.facebook.com/groups/joinsparkmedical