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Targeting G<sub>i/o</sub>-coupled GPCRs to inhibit nociceptors: Insights from the serotonin receptor Htr1b and triptans.

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Paper

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The authors' code

MATLAB · 70 lines · 2.2 KB · CC-BY-4.0

  1. clear
  3. d = daq("ni");
  5. addoutput(d,"Dev2","ao0","Voltage"); %trigger the Arduino - using analog to avoid clocking issues
  7. acquisitionDuration = 0.01;
  8. mode = "camera";
  9. if mode == "camera"
  10. triggerData = ones(acquisitionDuration*d.Rate,1)*2.5; %setting the analog trigger to high
  11. elseif mode == "led"
  12. triggerData = ones(acquisitionDuration*d.Rate,1)*5;
  13. end
  14. write(d,triggerData) %sending the analog trigger out
  15. disp(triggerData');
  16. % pause(0.001); %have it high for 1ms to allow the Arduino to register the trigger
  17. triggerData = 0; %setting the analog trigger back to 0
  18. write(d,triggerData); %sending the analog trigger out
  19. disp(triggerData');
  21. clear d;
  23. d = daq("ni");
  24. d.Rate = 10000;
  25. samplingRate = d.Rate;
  27. acquisitionDuration = 30; %in seconds
  28. duration = acquisitionDuration;
  30. ch1 = addinput(d,"Dev2","ai0","Voltage"); %accelerometer input
  31. ch1.TerminalConfig = "SingleEnded";
  32. ch2 = addinput(d,"Dev2","ai2","Voltage"); %voltage reading for pin-paw contact
  33. ch2.TerminalConfig = "SingleEnded";
  34. ch3 = addinput(d,"Dev2","ai4","Voltage"); %voltage command for solenoid
  35. ch3.TerminalConfig = "SingleEnded";
  37. data = read(d,seconds(acquisitionDuration));
  39. plot(data.Time, data.Variables)
  40. xlabel("Time (s)")
  41. ylabel("Amplitude")
  42. % legend(Dev1_2.Properties.VariableNames,"Interpreter","")
  44. clear d
  46. d = daq("ni");
  48. addoutput(d,"Dev2","ao0","Voltage"); %trigger the Arduino - using analog to avoid clocking issues
  50. acquisitionDuration = 0.01;
  51. triggerData = ones(acquisitionDuration*d.Rate,1)*5;
  52. write(d,triggerData) %sending the analog trigger out
  53. disp(triggerData');
  54. triggerData = 0; %setting the analog trigger back to 0
  55. write(d,triggerData); %sending the analog trigger out
  56. disp(triggerData');
  58. data.Properties.VariableNames(1) = "ai0";
  59. data.Properties.VariableNames(2) = "ai2";
  60. data.Properties.VariableNames(3) = "ai4";
  62. % duration = length(data.Time)/samplingRate;
  63. % temp = linspace(1/samplingRate,duration,duration*samplingRate);
  64. % temp = temp';
  65. % % data.Time = temp;
  67. save('D:\Karina\Experimental data\Pin Prick\Ex0159\KWH4_pinprick.mat',"data","duration","samplingRate");
  68. writetimetable(data,'D:\Karina\Experimental data\Pin Prick\Ex0159\KWH4_pinprick.csv');
  70. clear d;

PinPrickSetup_arduino.m, under CC-BY-4.0 · at the source

Overview

Authors: Jing Peng1,2, Brianna T Sanchez1,2, Anda M Chirila1,2,3, Xiangsunze Zeng1,4, Michelle M DeLisle1,2, Lijun Qi1,2, Jia Yin Xiao1,2, Karina Lezgiyeva1,2, Sarah A Low1,2,5, Clifford J Woolf1,4, Nikhil Sharma1,2,6, David D Ginty1,2
ORCID iDs: Anda M Chirila, David D Ginty
  1. Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
  2. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
  3. Department of Neuroscience, Brown University, Providence, RI 02912, USA
  4. F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Boston, MA 02115, USA
  5. Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
  6. Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10032, USA
Institutions: Howard Hughes Medical Institute (United States); Harvard University (United States); Brown University (United States); Boston Children's Hospital (United States); Columbia University (United States)
Journal: Cell reports. Medicine, volume 7, issue 8, article 102949
Dates: received 9 February 2026; accepted 3 July 2026; published online 30 July 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.xcrm.2026.102949 · PMID 42532046 · PMCID PMC13522807 · OpenAlex W7171831407
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: human (organism), mouse (organism), pain (population), cellular / molecular (subfield)
Methods: Evoked potentials, Statistics, fMRI & imaging, Single-unit activity, calcium imaging
Keywords: pain, somatosensory neurons, nociceptors, DRG, GPCRs, serotonin receptors, Htr1b, triptans, Gpr19
MeSH: Nociceptors*, Receptor, Serotonin, 5-HT1B*, Receptors, G-Protein-Coupled*, Tryptamines*, Animals, Ganglia, Spinal, Humans, Male, Mice, Oxazolidinones, Sumatriptan (* major topic)
Topic: Receptor Mechanisms and Signaling (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: NINDS NIH HHS (R35 NS097344, R35 NS105076, R35 NS132196); National Institutes of Health (AT011447, NS132196-02, NS097344-05, NS105076-01); Howard Hughes Medical Institute; Ono Pharmaceutical Co., Ltd; NCCIH NIH HHS (R01 AT011447); NIGMS NIH HHS (T32 GM089626)
Citations: not cited yet (Europe PMC); 98 references in the paper
Research resources: Mouse: wt: C57Bl/6J RRID:IMSR_JAX:000664, RRID:IMSR_JAX:003724, RRID:IMSR_JAX:005703, RRID:IMSR_JAX:024109, RRID:IMSR_JAX:028865, RRID:IMSR_JAX:030328, RRID:IMSR_JAX:032027, RRID:IMSR_JAX:034112, RRID:IMSR_JAX:036564, Mouse: Bmpr1bCre RRID:IMSR_JAX:039561, Mouse: Smr2Cre: Smr2tm1(cre)Ddg/J RRID:IMSR_JAX:039562, MATLAB RRID:SCR_001622, Arduino IDE RRID:SCR_024884

Abstract

Pain perception is initiated upon activation of nociceptors of the dorsal root ganglia (DRG) and trigeminal ganglia. We identify G-protein-coupled receptors (GPCRs) expressed in CGRP+ mouse and human DRG neurons and find that agonists of several identified Gi/o-coupled and orphan GPCRs attenuate neuronal excitability. Experiments focusing on the Gi/o-coupled serotonin receptor Htr1b, which is expressed in mouse and human CGRP+ DRG neurons, reveal that Htr1b/1d agonists, the triptans sumatriptan and zolmitriptan, attenuate CGRP+ neuron excitability in vitro and exhibit analgesia across several pain models, including neuropathic pain. Conditional genetic deletion experiments show that triptan-induced analgesia is mediated by Htr1b expressed in A-fiber mechanonociceptors. Also, triptan-associated adverse effects are partially mediated by Htr1b-independent targets. Further testing identifies the GPCR Gpr19 as an additional promising target for treating pain. These findings establish a preclinical screening platform for identifying analgesic candidates and reveal nociceptor GPCRs that may be targeted to treat pain.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above.

Zenodo 20801945

License: CC-BY-4.0
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Size: 1 file
Software Heritage: not checked
Found in: the text, “Quantification and statistical analysis”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
  • 27 September 2026: the link answers (HTTP 200)
4 files
At the source: doi.org/10.5281/zenodo.20801945

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 3 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data and code availability

All data reported in this study will be shared by the lead contact upon request.

All original code has been deposited at Zenodo and is publicly available at https://doi.org/10.5281/zenodo.20801945 as of the date of publication.

Any additional information required to reanalyze the data reported in this work is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Authors: added David D Ginty (0000-0001-9723-8530); removed David D Ginty

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 9 keywords, 11 MeSH terms, 6 funders, 97 references, 13 RRIDs.

Cite

This paper

Peng, J., Sanchez, B. T., Chirila, A. M., Zeng, X., DeLisle, M. M., Qi, L., Xiao, J. Y., Lezgiyeva, K., Low, S. A., Woolf, C. J., Sharma, N., & Ginty, D. D. (2026). Targeting G<sub>i/o</sub>-coupled GPCRs to inhibit nociceptors: Insights from the serotonin receptor Htr1b and triptans. Cell reports. Medicine, 7(8), 102949. https://doi.org/10.1016/j.xcrm.2026.102949

BibTeX

@article{peng2026targeting,
author = {Peng, Jing and Sanchez, Brianna T and Chirila, Anda M and Zeng, Xiangsunze and DeLisle, Michelle M and Qi, Lijun and Xiao, Jia Yin and Lezgiyeva, Karina and Low, Sarah A and Woolf, Clifford J and Sharma, Nikhil and Ginty, David D},
title = {{Targeting G\<sub\>i/o\</sub\>-coupled GPCRs to inhibit nociceptors: Insights from the serotonin receptor Htr1b and triptans}},
journal = {Cell reports. Medicine},
year = {2026},
month = jul,
volume = {7},
number = {8},
pages = {102949},
publisher = {Elsevier},
issn = {2666-3791},
doi = {10.1016/j.xcrm.2026.102949},
url = {https://doi.org/10.1016/j.xcrm.2026.102949},
pmid = {42532046},
pmcid = {PMC13522807}
}

RIS

TY - JOUR
AU - Peng, Jing
AU - Sanchez, Brianna T
AU - Chirila, Anda M
AU - Zeng, Xiangsunze
AU - DeLisle, Michelle M
AU - Qi, Lijun
AU - Xiao, Jia Yin
AU - Lezgiyeva, Karina
AU - Low, Sarah A
AU - Woolf, Clifford J
AU - Sharma, Nikhil
AU - Ginty, David D
TI - Targeting G<sub>i/o</sub>-coupled GPCRs to inhibit nociceptors: Insights from the serotonin receptor Htr1b and triptans
T2 - Cell reports. Medicine
J2 - Cell Rep Med
PY - 2026
DA - 2026/07/30
VL - 7
IS - 8
SP - 102949
SN - 2666-3791
PB - Elsevier
DO - 10.1016/j.xcrm.2026.102949
UR - https://doi.org/10.1016/j.xcrm.2026.102949
LA - en
ER -

CSL-JSON

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"id": "10.1016/j.xcrm.2026.102949",
"type": "article-journal",
"title": "Targeting G<sub>i/o</sub>-coupled GPCRs to inhibit nociceptors: Insights from the serotonin receptor Htr1b and triptans",
"container-title": "Cell reports. Medicine",
"author": [
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"family": "Peng",
"given": "Jing"
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"family": "Sanchez",
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},
{
"family": "Chirila",
"given": "Anda M"
},
{
"family": "Zeng",
"given": "Xiangsunze"
},
{
"family": "DeLisle",
"given": "Michelle M"
},
{
"family": "Qi",
"given": "Lijun"
},
{
"family": "Xiao",
"given": "Jia Yin"
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{
"family": "Lezgiyeva",
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}
],
"container-title-short": "Cell Rep Med",
"volume": "7",
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"DOI": "10.1016/j.xcrm.2026.102949",
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"PMCID": "PMC13522807",
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