Obesity increases nociceptive activation of the trigeminal system
Open accessAbstract
Background: Obesity is a risk factor associated with several pain syndromes. However, the mechanisms underlying the association between obesity and pain are not known. The aim of this study was to test the hypothesis that obesity enhances neuronal responses to nociceptive stimulation within the trigeminal nucleus caudalis (TNC). Methods: Male and female C57BL/6J mice were fed a high‐fat or regular diet from the time of weaning until 20 weeks of age. We then quantified neuronal activation by measuring F os immunoreactivity within the TNC in response to a facial injection of a low dose of capsaicin (1 μg/10 μL). Results: We found that 0.01% capsaicin did not significantly increase F os immunoreactivity in control mice fed a regular diet. In contrast, this low dose of capsaicin caused a 3.3‐fold increase in F os in the TNC in obese mice (p < 0.001). Conclusions: These results support the hypothesis that diet‐induced obesity in mice enhances nociceptive processing within the TNC. Diet‐induced obesity may be a useful model for mechanistic studies. Future studies will improve our understanding of how obesity may contribute to trigeminal pain by sensitizing the trigeminal nociceptive system.
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The reductions in nerve endings and network complexity suggest a potential mechanism for sensory alterations in obesity, including reduced sensitivity to whisker stimulation and aberrant sensory and pain processing previously observed in obese mice.
“The reductions in nerve endings and network complexity suggest a potential mechanism for sensory alterations in obesity, including the reduced sensitivity to whisker stimulation observed by us and the aberrant sensory and pain processing previously observed in obese mice30–32.”
From A deep-learning framework reveals whole-body perturbations at cell level (2026) · cites this paper as [30]
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1 retracted
Flores, M. B. S., Rocha, G. Z., Damas-Souza, D. M., Osório–Costa, F., Dias, M. M., Ropelle, E. R., de Camargo, J. A., de Carvalho, R. B., Carvalho, H. F., Saad, M. J. A., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.05.045 · Cited by 68 · see citing works
RetractedThe capsaicin receptor: a heat-activated ion channel in the pain pathway
Caterina, M. J., Schumacher, M. A., Tominaga, M., Rosen, T. A., Levine, J. D., & Julius, D. J. (1997) · Nature · doi:10.1038/39807 · Cited by 9,132 · see citing works
Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.
Flegal, K., Carroll, M., Kit, B., & Ogden, C. (2012) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2012.39 · Cited by 5,523 · see citing works
Central sensitization: a generator of pain hypersensitivity by central neural plasticity
Latremoliere, A., & Woolf, C. J. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2009.06.012 · Cited by 3,913 · see citing works
Induction of c-fos-like protein in spinal cord neurons following sensory stimulation
Hunt, S. P., Pini, A., & Evan, G. I. (1987) · Nature · doi:10.1038/328632a0 · Cited by 1,986 · see citing works
Migraine — Current Understanding and Treatment
Goadsby, P. J., Lipton, R. B., & Ferrari, M. D. (2002) · New England Journal of Medicine · doi:10.1056/nejmra010917 · Cited by 1,920 · see citing works
High-fat diet-induced obesity in animal models
Hariri, N., & Thibault, L. (2010) · Nutrition Research Reviews · doi:10.1017/s0954422410000168 · Cited by 1,090 · see citing works
Burstein, R., Yamamura, H., Malick, A., & Strassman, A. M. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.2.964 · Cited by 607 · see citing works
Fatty acids and inflammation: The cutting edge between food and pharma
Calder, P. C. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.05.085 · Cited by 518 · see citing works
Using c-fos as a Neural Marker of Pain
Harris, J. A. (1998) · Brain Research Bulletin · doi:10.1016/s0361-9230(97)00277-3 · Cited by 482 · see citing works
Hc, H., McMillen, R. C., Neaves, T. T., Koch, K., & Cosby, A. G. (2007) · Journal of Pain · doi:10.1016/j.jpain.2006.12.003 · Cited by 268 · see citing works
Tumor Necrosis Factor- in Sera of Obese Patients: Fall with Weight Loss
Dandona, P. (1998) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.8.2907 · Cited by 176 · see citing works
Puig, K. L., Floden, A. M., Adhikari, R., Golovko, M. Y., & Combs, C. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030378 · Cited by 152 · see citing works
Luccarini, P., Childeric, A., Gaydier, A.-M., Voisin, D. L., & Dallel, R. (2006) · Journal of Pain · doi:10.1016/j.jpain.2006.04.010 · Cited by 140 · see citing works
Nozaki, K., Boccalini, P., & Moskowitz, M. A. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90235-t · Cited by 134 · see citing works
Strassman, A., Mineta, Y., & Vos, B. P. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-06-03725.1994 · Cited by 133 · see citing works
Obesity and the Impact of Chronic Pain
Marcus, D. A. (2004) · Clinical Journal of Pain · doi:10.1097/00002508-200405000-00009 · Cited by 133 · see citing works
The orofacial capsaicin test in rats: effects of different capsaicin concentrations and morphine
Pélissier, T., Pajot, J., & Dallel, R. (2002) · Pain · doi:10.1016/s0304-3959(01)00432-8 · Cited by 121 · see citing works
Calcitonin gene-related peptide receptor antagonist olcegepant acts in the spinal trigeminal nucleus
Sixt, M.-L., Meßlinger, K., & Fischer, M. J. M. (2009) · Brain · doi:10.1093/brain/awp168 · Cited by 93 · see citing works
Tumor necrosis factor α enhances the sensitivity of rat trigeminal neurons to capsaicin
khan, A. W. A., Diogenes, A. R., Jeske, N. A., Henry, M. A., Akopian, A. N., & Hargreaves, K. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.05.036 · Cited by 82 · see citing works
Trigeminal pain and quantitative sensory testing in painful peripheral diabetic neuropathy
Arap, A., de Siqueira, S. R. D. T., Silva, C. B., Teixeira, M. J., & de Siqueira, J. T. T. (2010) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2010.03.021 · Cited by 65 · see citing works
Álvarez, P., Saavedra, G., Hernández, A., Paeile, C., & Pélissier, T. (2003) · Anesthesiology · doi:10.1097/00000542-200310000-00033 · Cited by 35 · see citing works
Hagenacker, T., Czeschik, J. C., Schäfers, M., & Büsselberg, D. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.09.012 · Cited by 35 · see citing works
Mitsikostas, D., del Río, M. S., & Waeber, C. (2002) · Cephalalgia · doi:10.1046/j.1468-2982.2002.00382.x · Cited by 31 · see citing works
Managing pain in obese patients
D’Arcy, Y. M. (2011) · The Nurse Practitioner · doi:10.1097/01.npr.0000407601.90514.52 · Cited by 10 · see citing works
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
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Siracusa, R., Paola, R. D., Cuzzocrea, S., & Impellizzeri, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083891 · Cited by 710 · see citing works
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Sluka, K. A., & Clauw, D. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.06.006 · Cited by 671 · see citing works
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Bjørklund, G., Aaseth, J., Doşa, M. D., Pivina, L. M., Dadar, M., Pen, J. J., & Chirumbolo, S. (2019) · Nutrition · doi:10.1016/j.nut.2019.04.007 · Cited by 78 · see citing works
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Martins-Oliveira, M., Akerman, S., Holland, P. R., Hoffmann, J., Tavares, I., & Goadsby, P. J. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.01.005 · Cited by 58 · see citing works
Westgate, C. S. J., Israelsen, I. M. E., Jensen, R., & Eftekhari, S. (2021) · The Journal of Headache and Pain · doi:10.1186/s10194-021-01337-0 · Cited by 55 · see citing works
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Markkula, R. A., Kalso, E. A., & Kaprio, J. A. (2016) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-016-0873-6 · Cited by 42 · see citing works
Interictal amylin levels in chronic migraine patients: A case-control study
Irimia, P., Martínez-Valbuena, I., Mínguez‐Olaondo, A., Domínguez‐Vivero, C., Sánchez-Arias, J. A., Martínez‐Vila, E., Luquín, M. R., & Leira, R. (2020) · Cephalalgia · doi:10.1177/0333102420977106 · Cited by 42 · see citing works
Marics, B., Peitl, B., Varga, A., Pázmándi, K., Bácsi, A., Németh, J., Szilvássy, Z., Jancsó, G., & Dux, M. (2016) · Cephalalgia · doi:10.1177/0333102416654883 · Cited by 39 · see citing works
Liang, Y., Feng, S., Qi, Y.-P., Li, K., Jin, Z., Jing, H., Liu, L., Cai, J., Xing, G., & Fu, K. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.05.026 · Cited by 39 · see citing works
Loredo‐Pérez, A. A., Montalvo‐Blanco, C. E., Hernández‐González, L. I., Anaya-Reyes, M., del Valle‐Laisequilla, C. F., Reyes‐García, G., Acosta‐González, R. I., Martínez-Martínez, A., Villarreal-Salcido, J., Vargas-Muñoz, V. M., et al. (2016) · Obesity · doi:10.1002/oby.21485 · Cited by 32 · see citing works
Martins-Oliveira, M., Tavares, I., & Goadsby, P. J. (2021) · Brain Research · doi:10.1016/j.brainres.2021.147629 · Cited by 30 · see citing works
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Guo, X., Tao, X., Tong, Q., Li, T., Dong, D., Zhang, B., Zhao, M., & Song, T. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.10368 · Cited by 27 · see citing works
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Glovak, Z. T., Mihalko, S., Baghdoyan, H. A., & Lydic, R. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.09.012 · Cited by 14 · see citing works
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Brandão, A. D. F., Bonet, I. J. M., Pagliusi, M., Zanetti, G. G., Pho, N., Tambeli, C. H., Parada, C. A., Vieira, A. S., & Sartori, C. R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01453 · Cited by 13 · see citing works
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Watson, S. L., Watson, C. J., Baghdoyan, H. A., & Lydic, R. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.06.025 · Cited by 9 · see citing works
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Vatsa, N., Dave, E. K., Higgins, M. K., Huang, J., Desai, S., Gold, D. A., Gold, M. E., Jain, V., Fatade, Y. A., Rahbar, A., et al. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.123.031429 · Cited by 5 · see citing works
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- Authors
- Rossi, H. L., Luu, A. K. S., DeVilbiss, J. L., & Recober, A.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Recober, A.
- ORCID
- Rossi, H.L.
- Venue
- European Journal of Pain
- Publisher
- Wiley
- Published
- 2012-10-16
- Volume
- 17
- Issue
- 5
- Pages
- 649-653
- ISSN
- 1090-3801 (ISSN-L)
- 1532-2149
- PMC
- PMC4275045
- OpenAlex
- W2158781355
- Cited by
- 33
- References
- 26
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2021: 4 · 2020: 3 · 2019: 4 · 2017: 4 · 2016: 7 · 2015: 1 · 2014: 1 · 2013: 2
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Pain (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K08NS066087, K08-NS066087-01, T32NS045549)
- National Center for Research Resources (UL1RR024979)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Keywords
- obesity, trigeminal nucleus caudalis, nociception, trigeminal pain, capsaicin, Fos-like immunoreactivity, high-fat diet, diet-induced obesity, pain sensitization
- MeSH terms
- Animals, Capsaicin, Female, Male, Mice, Inbred C57BL, Neurons, Obesity, Pain, Trigeminal Caudal Nucleus, Proto-Oncogene Proteins c-fos, Mice, Nociceptive Pain, Diet, High-Fat
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