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TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain
Kobayashi M, Konishi H, Sayo A, Takai T, Kiyama H.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016-10-01
Topic: Brain proteins, microglia and lab models
Neuropathic pain afflicts millions of people, and the development of an effective treatment for this intractable pain is an urgent issue. Recent evidence has implicated microglia in neuropathic pain. The present study showed that the DNAX-activating protein of 12 kDa (DAP12) and its associated "triggering receptor expressed on myeloid cells 2" (TREM2) were predominantly expressed by microglia in the dorsal horn after spinal nerve injury, revealing a role for TREM2/DAP12 signaling in neuropathic pain.
Key findings
- Recent evidence has implicated microglia in neuropathic pain.
- The present study showed that the DNAX-activating protein of 12 kDa (DAP12) and its associated "triggering receptor expressed on myeloid cells 2" (TREM2) were predominantly expressed by microglia in the dorsal horn after spinal nerve injury, revealing a role for TREM2/DAP12 signaling in neuropathic pain.
- Nerve injury-induced proinflammatory cytokine expression in microglia and pain behaviors were significantly suppressed in Dap12-deficient mice.
- Furthermore, intrathecal administration of TREM2 agonistic antibody induced proinflammatory cytokine expression, as well as neuropathic pain, in mice without nerve injury.
Why it matters
In mice, TREM2/DAP12 signaling in microglia promoted inflammation and worsened neuropathic pain, and blocking it reduced pain behaviors. This is about pain after nerve injury in mice, not Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 161 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.4 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 10.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 18 other studies in this library |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Hiroshi Kiyama: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Japan Science and Technology Agency: institution h-index 880 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27798193) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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Read the original
- DOI: 10.1523/jneurosci.1238-16.2016
- PubMed: 27798193
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Kobayashi, M., Konishi, H., Sayo, A., Takai, T., & Kiyama, H. (2016). TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.1238-16.2016
Vancouver
Kobayashi M, Konishi H, Sayo A, Takai T, Kiyama H. TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2016. doi:10.1523/jneurosci.1238-16.2016. PMID: 27798193.
BibTeX
@article{kobayashi2016-27798193,
author = {Kobayashi, M. and Konishi, H. and Sayo, A. and Takai, T. and Kiyama, H.},
title = {{TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2016},
doi = {10.1523/jneurosci.1238-16.2016},
pmid = {27798193},
url = {https://doi.org/10.1523/jneurosci.1238-16.2016}
}
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