Evidence map›Paper›PMID 42825602›Full record

ArticlePain2026

Cannabinoid actions in a nonsurgical mouse model of sensitized dural nociceptors.

Yoshihiro Kitaoka, Kyle L Whyland, Zhiwei Li, Kyotaro Koshika, Toru Yamamoto, Yatendra Mulpuri, Igor Spigelman

Abstract read
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In one paragraph

Article in Pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Yoshihiro KitaokaLaboratory of Neuropharmacology, Section of Biosystems and Function, School of Dentistry, University of California, Los Angeles, CA, United States.
Kyle L WhylandLaboratory of Neuropharmacology, Section of Biosystems and Function, School of Dentistry, University of California, Los Angeles, CA, United States.
Zhiwei LiLaboratory of Neuropharmacology, Section of Biosystems and Function, School of Dentistry, University of California, Los Angeles, CA, United States.
Kyotaro KoshikaDepartment of Dental Anesthesiology, Tokyo Dental College, Tokyo, Japan.
Toru YamamotoDivision of Dental Anesthesiology, Niigata University, Niigata, Japan.
Yatendra MulpuriCollege of Dentistry, New York University, New York, NY, United States.
Igor SpigelmanLaboratory of Neuropharmacology, Section of Biosystems and Function, School of Dentistry, University of California, Los Angeles, CA, United States.ORCID 0000-0001-6489-5454

Funding

Blink, Lacrimation, and Nociception: Precision Mapping and Integrated Atlas Generation of Corneal Trigeminal AfferentsU01EY034687 · NEI · DUKE UNIVERSITY · PI Sina Farsiu, Victor L Perez · 2022 to 2026
$6.4M
Clinical and Translational Science Institute, University of California, Los Angeles UL1TR000124Clinical and Translational Science Institute, University of California, Los Angeles UL1TR001881NEI NIH HHS U01EY034687NINDS NIH HHS NS128148
6 · The paper itself

Abstract

abstractCannabinoid 1 and 2 receptor (CB1R and CB2R) agonists alleviate inflammatory and neuropathic pain symptoms. However, central nervous system (CNS) side effects mediated by CB1Rs limit their widespread use. We developed peripherally restricted cannabinoids (PRCBs), which exhibit analgesic efficacy with minimal CNS side effects. Here, we examined PRCB actions in a mouse model of dural acid-induced hypersensitivity. Supradural injections of pH-6.0 (but not pH-7.4) saline (4.5 µL) in five-week-old female C57BL/6J mice induced periorbital allodynia (assessed with von Frey filaments) with recovery by 48 hours. By 72 hours, allodynia was elicited with a supradural pH-7.0 saline injection in pH-6.0 (but not pH-7.4) mice. The CB1R/CB2R agonist PRCB, 4-{2-[(1E)-1-[(4-propylnaphthalen-1-yl) methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) (5 µM) or the selective CB1R agonist arachidonyl-2'-chloroethylamide (ACEA, 5 µM), coapplied with pH-6.0 saline, prevented both the initial and latent allodynia, but coadministering pH 6.0 with the CB2R-selective agonist RNB61 (5 µM) did not. Coadministering pH-6.0/PrNMI with CB1R- or CB2R-selective inverse agonists abolished the preventative effects of PrNMI. Supradural pH-6.0 saline-evoked allodynia followed 72 hours later by coadministration of pH 7.0/PrNMI did not prevent latent allodynia. Patch recordings obtained from dural trigeminal ganglion neurons (dTGNs) acutely isolated from FluoroGold/pH-6.0 (but not pH-7.4)-injected mice had larger acid-induced depolarizations. All dTGNs had electrophysiological properties of Aδ- or C-type nociceptors. PrNMI (1 µM) suppressed acid-induced depolarizations in dTGNs from pH-7.4 (but not pH-6.0)-treated mice, whereas RNB61 (0.5 µM) had no effect. These findings indicate that PrNMI prevents acid-induced sensitization by coactivating neuronal CB1Rs and non-neuronal CB2Rs. Cannabinoid 2 receptor activation alone is insufficient, and once sensitized, combined CB1R/CB2R activation loses efficacy.

Indexed as

Acid-sensing ion channelCannabinoidDura materMigraineNociceptor sensitizationTrigeminal ganglion

Identifiers

PMID42825602

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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 OpenQuestion graph.