Evidence map›Paper›PMID 40689848›Full record

ReviewEuropean journal of pain (London, England)2025

The Role of Peripheral N-Methyl-D-Asparate (NMDA) Receptors in Itch and Pain: A Narrative Review.

Ryusuke Tanaka, Silvia Lo Vecchio, Giulia Erica Aliotta, Lars Arendt-Nielsen

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in European journal of pain (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Itching, Ionic Channels, Immune System, Magnesium and Antioxidants.Clinical, cosmetic and investigational dermatology · 2026
    Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Ryusuke TanakaDepartment of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark.
Silvia Lo VecchioDepartment of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark.ORCID https://orcid.org/0000-0001-6548-2459
Giulia Erica AliottaDepartment of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark.
Lars Arendt-NielsenDepartment of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveNMDA receptors, predominantly located in the central nervous system and known for their roles in synaptic plasticity and central sensitisation of pain and itch, are also expressed in peripheral sensory neurons. Emerging evidence suggests that peripheral NMDA receptors contribute to pathological pain and potentially itch, identifying them as promising therapeutic targets. The aim of this review is to explore the role of peripheral NMDA receptors in pain and itch and to summarise the effectiveness of topical NMDA antagonists in managing these sensations. DATABASES AND DATA TREATMENT: This review was conducted through a systematic search of the PubMed database using MeSH terms and keywords related to 'peripheral NMDA receptors', 'pain', 'itch' and 'topical ketamine'. Additional references were included based on expert knowledge and reference tracking. Only English-language articles were considered.

resultsAnimal studies demonstrate that peripheral NMDA receptors are involved in inflammatory and certain neuropathic pain models, with antagonists showing analgesic effects. Limited studies also suggest their role in non-histaminergic itch through glutamate signalling. In humans, topical ketamine has shown mixed results for pain relief, and preliminary clinical reports suggest potential antipruritic effects. However, controlled clinical trials, particularly for itch, are lacking.

conclusionPeripheral NMDA receptors are involved in the transmission and sensitisation of both pain and itch, especially under pathological conditions. While topical ketamine may offer therapeutic benefits, particularly for non-histaminergic itch and neuropathic pain, further clinical research is necessary to confirm its efficacy, safety and optimal use. SIGNIFICANCE STATEMENT: This review highlights the underexplored role of peripheral NMDA receptors in itch, especially non-histaminergic pathways, and synthesises emerging evidence for their therapeutic potential. By comparing pain and itch mechanisms, it suggests that topical ketamine could serve as novel treatments for refractory itch and localised pain, warranting further clinical investigation.

Indexed as

NeuralgiaPainPruritusReceptors, N-Methyl-D-AspartateAnimalsHumansKetamineKetamineReceptors, N-Methyl-D-Aspartate

Identifiers

PMID40689848
PMCPMC12279002

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.