Gonadectomy Affects Hormonal and Behavioral Responses to Repetitive Nociceptive Stimulation in Male Rats
Abstract
A bstract: Sex differences have been observed repeatedly in chronic pain syndromes in both humans and animals, with females showing a higher incidence; it is likely that the gonadal hormones are responsible for these differences. To examine the role of male gonadal hormones on repetitive nociceptive stimulation, we studied male rats, half of them gonadectomized (GDX) and half left intact (INT). Starting from the third week after gonadectomy, they were subjected to the formalin test once a week for 3 weeks (50 μl formalin 5% injected s.c. in the dorsum of the hind paw: right, left, and right). Formalin‐induced licking, flexing, and jerking of the injected paw were recorded and analyzed for each of the three trials. Analysis of variance showed significant differences between GDX and INT animals depending on the trial considered: Trial 1: the GDX and INT groups showed a similar amount of licking, flexing, and paw‐jerk; Trials 2 and 3: these responses showed a sort of adaptation in INT animals, not present in the GDX ones, resulting in lower levels of pain responses in INT than GDX. Corticosterone was higher in GDX animals than in INT animals. Testosterone plasma levels were drastically decreased by gonadectomy, whereas estradiol was increased. These data indicate that male gonadal hormones play a key role in inhibiting the behavioral responses to repeated nociceptive stimulation. This suggests that the lower incidence of chronic pain syndromes in males could be caused by the presence of these hormones.
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The higher presence of pain in females might be explained by several factors: influence of sexual hormones, differences in emotional experiences and coping strategies, and differences in social and occupational roles [71, 72].
“The higher presence of pain in females might be explained by several factors [71, 72]: (1) influence of sexual hormones (e.g., gonadal hormones); (2) differences in emotional experiences and coping strategies; and (3) differences in social and occupational roles.”
From Psychological variables associated with quality of life in patients with head and neck cancer: the role of body image distress (2022) · cites this paper as [71]
Cites
Ethical guidelines for investigations of experimental pain in conscious animals.
Zimmermann, M. (1983) · Pain · doi:10.1016/0304-3959(83)90201-4 · Cited by 7,762 · see citing works
Berkley, K. J. (1997) · Behavioral and Brain Sciences · doi:10.1017/s0140525x97221485 · Cited by 1,125 · see citing works
Handa, R. J., Nunley, K. M., Lorens, S. A., Louie, J. P., McGivern, R. F., & Bollnow, M. R. (1994) · Physiology & Behavior · doi:10.1016/0031-9384(94)90018-3 · Cited by 325 · see citing works
Perspective: Nonreproductive Sites of Action of Reproductive Hormones
Manolagas, S. C., & Kousteni, S. (2001) · Endocrinology · doi:10.1210/endo.142.6.8221 · Cited by 100 · see citing works
Aloisi, A. M., & Ceccarelli, I. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00445-5 · Cited by 98 · see citing works
Self-citationViau, V., Soriano, L., & Dallman, M. F. (2001) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2001.00653.x · Cited by 97 · see citing works
Gozariu, M., Bragard, D., Willer, J. C., & Bars, D. L. (1997) · Journal of Neurophysiology · doi:10.1152/jn.1997.78.6.3165 · Cited by 94 · see citing works
A PROTECTIVE ROLE FOR TESTOSTERONE IN ADJUVANT-INDUCED ARTHRITIS
Harbuz, M. S., PERVEEN-GILL, Z., Lightman, S. L., & Jessop, D. S. (1995) · Lara D. Veeken · doi:10.1093/rheumatology/34.12.1117 · Cited by 78 · see citing works
Alteration of Descending Modulation of Nociception during the Course of Monoarthritis in the Rat
Danziger, N., Weil-Fugazza, J., Bars, D. L., & Bouhassira, D. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-06-02394.1999 · Cited by 75 · see citing works
Kærgaard, A., Hansen, Å. M., Rasmussen, K., & Andersen, J. H. (2000) · Scandinavian Journal of Work Environment & Health · doi:10.5271/sjweh.545 · Cited by 40 · see citing works
Aloisi, A. M., Albonetti, M. E., & Carli, G. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00232-1 · Cited by 38 · see citing works
Self-citationGogas, K. R., Levine, J. D., & Basbaum, A. I. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12366-5 · Cited by 34 · see citing works
Hadid, R., Spinedi, E., Daneva, T., Grau, G. E., & Gaillard, R. C. (2008) · Neuroendocrinology · doi:10.1159/000127024 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Studying sex and gender differences in pain and analgesia: a consensus report
Greenspan, J. D., Craft, R. M., LeResche, L., Arendt-Nielsen, L., Berkley, K. J., Fillingim, R. B., Gold, M. S., Holdcroft, A., Lautenbacher, S., Mayer, E. A., et al. (2007) · Pain · doi:10.1016/j.pain.2007.10.014 · Cited by 1,033 · see citing works
Insights into the mechanisms and the emergence of sex-differences in pain
Melchior, M., Poisbeau, P., Gaumond, I., & Marchand, S. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.05.007 · Cited by 143 · see citing works
Basaria, S., Travison, T. G., Alford, D., Knapp, P. E., Teeter, K., Cahalan, C., Eder, R., Lakshman, K., Bachman, E., Mensing, G., et al. (2015) · Pain · doi:10.1097/01.j.pain.0000460308.86819.aa · Cited by 125 · see citing works
The influence of sex hormones on musculoskeletal pain and osteoarthritis
Gulati, M., Dursun, E., Vincent, K., & Watt, F. E. (2023) · The Lancet Rheumatology · doi:10.1016/s2665-9913(23)00060-7 · Cited by 122 · see citing works
Sex differences and hormonal modulation of deep tissue pain
Traub, R. J., & Ji, Y. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.07.002 · Cited by 83 · see citing works
Estrogens and phytoestrogens in body functions
Ceccarelli, I., Bioletti, L., Peparini, S., Solomita, E., Ricci, C., Casini, I., Miceli, E., & Aloisi, A. M. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.007 · Cited by 84 · see citing works
Self-citationSex differences in the relationships between parasympathetic activity and pain modulation
Nahman‐Averbuch, H., Dayan, L., Sprecher, E., Hochberg, U., Brill, S., Yarnitsky, D., & Jacob, G. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.11.004 · Cited by 66 · see citing works
Glial and neuroimmune cell choreography in sexually dimorphic pain signaling
Midavaine, É., Côté, J., Marchand, S., & Sarret, P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.01.023 · Cited by 67 · see citing works
LaPrairie, J. L., & Murphy, A. Z. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.02.001 · Cited by 60 · see citing works
A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients
White, H. D., & Robinson, T. D. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.05.020 · Cited by 59 · see citing works
Sex differences in inflammation and inflammatory pain in cyclooxygenase-deficient mice
Chillingworth, N. L., Morham, S. G., & Donaldson, L. F. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00901.2005 · Cited by 58 · see citing works
Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral Hypersensitivity in Rats
Ji, Y., Hu, B., Li, J., & Traub, R. J. (2018) · Journal of Pain · doi:10.1016/j.jpain.2018.02.007 · Cited by 57 · see citing works
Endogenous pain modulation during the formalin test in estrogen receptor beta knockout mice
Spooner, M.-F., Robichaud, P., Carrier, J. C., & Marchand, S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.09.037 · Cited by 47 · see citing works
Alterations in pain during adolescence and puberty
Nahman‐Averbuch, H., Li, R., Boerner, K. E., Lewis, C. A., Garwood, S., Palermo, T. M., & Jordan, A. L. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.01.006 · Cited by 44 · see citing works
Gagliano‐Jucá, T., Travison, T. G., Nguyen, P. L., Kantoff, P. W., Taplin, M., Kibel, A. S., Manley, R., Hally, K., Bearup, R., Beleva, Y. M., et al. (2017) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2017.09.017 · Cited by 34 · see citing works
Sex differences in complex regional pain syndrome type I (CRPS-I) in mice
Tang, C., Li, J., Tai, W. L., Yao, W., Zhao, B., Hong, J., Shi, S., Wang, S., & Xia, Z. (2017) · Journal of Pain Research · doi:10.2147/jpr.s139365 · Cited by 32 · see citing works
Malheiros, J. M., Lima, M. M. S., Avanzi, R. D. T., da Silva, S. G., Suchecki, D., Guinsburg, R., & Covolan, L. (2013) · Hippocampus · doi:10.1002/hipo.22235 · Cited by 30 · see citing works
How Sex Hormones Affect Migraine: An Interdisciplinary Preclinical Research Panel Review
Godley, F. A., Meitzen, J., Nahman‐Averbuch, H., O’Neal, M. A., Yeomans, D. C., Santoro, N. F., Riggins, N., & Edvinsson, L. I. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14020184 · Cited by 30 · see citing works
Strand, N. H., D'Souza, R. S., Gomez, D. A., Whitney, M. A., Attanti, S., Anderson, M. A., Moeschler, S. M., Chadwick, A. L., & Maloney, J. A. (2024) · Maturitas · doi:10.1016/j.maturitas.2024.108135 · Cited by 30 · see citing works
Neurosteroids and neuropathic pain management: Basic evidence and therapeutic perspectives
Meyer, L., Taleb, O., Patte-Mensah, C., & Mensah-Nyagan, A.-G. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100795 · Cited by 30 · see citing works
Raheem, O. A., Patel, S. H., Sisul, D., Furnish, T. J., & Hsieh, T.-C. (2017) · American Journal of Men's Health · doi:10.1177/1557988316672396 · Cited by 29 · see citing works
Taiwo, O. B., Kovács, K. J., Sun, Y., & Larson, A. A. (2005) · Pain · doi:10.1016/j.pain.2004.12.002 · Cited by 28 · see citing works
Huang, G., Travison, T., Maggio, M., Edwards, R. R., & Basaria, S. (2016) · Clinical Endocrinology · doi:10.1111/cen.13049 · Cited by 26 · see citing works
Arthuri, M. T., Gameiro, G. H., Tambeli, C. H., & Veiga, M. C. F. D. A. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.10.019 · Cited by 23 · see citing works
Nociceptor Overexpression of NaV1.7 Contributes to Chronic Muscle Pain Induced by Early-Life Stress
Álvarez, P., Bogen, O., Green, P. G., & Levine, J. D. (2021) · Journal of Pain · doi:10.1016/j.jpain.2021.02.003 · Cited by 19 · see citing works
Pain in head and neck cancer patients: the role of gender.
Bianchini, C., Corazzi, V., Malagò, M., Bellini, T., Stomeo, F., Ciorba, A., & Pelucchi, S. (2019) · PubMed · Cited by 18 · see citing works
Headache prevalence in transgender and gender diverse youth: A single‐center case–control study
Hranilovich, J. A., & Millington, K. (2023) · Headache The Journal of Head and Face Pain · doi:10.1111/head.14493 · Cited by 17 · see citing works
Cerea, S., Sansoni, M., Scarzello, G., Groff, E., & Ghisi, M. (2022) · Supportive Care in Cancer · doi:10.1007/s00520-022-07334-6 · Cited by 15 · see citing works
“The higher presence of pain in females might be explained by several factors [71, 72]: (1) influence of sexual hormones (e.”
BackgroundHuang, G. T.-W., Travison, T. G., Edwards, R. R., & Basaria, S. S. (2016) · Pain Medicine · doi:10.1093/pm/pnw159 · Cited by 15 · see citing works
Can fibromyalgia be considered a characteristic symptom of climacterium?
Erkan, İ. B. Ö., Erel, C. T., & Durmuşoğlu, F. (2021) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2021-140336 · Cited by 13 · see citing works
Кошурба, І. В., Hladkykh, F. V., Chyzh, M., Belochkіna, I., & Rublova, T. V. (2022) · Fìzìologìčnij žurnal · doi:10.15407/fz68.05.025 · Cited by 13 · see citing works
Estrogens Suppress Spinal Endomorphin 2 Release in Female Rats in Phase with the Estrous Cycle
Kumar, A., Storman, E. M., Liu, N., & Gintzler, A. R. (2015) · Neuroendocrinology · doi:10.1159/000430817 · Cited by 13 · see citing works
SEX DIFFERENCES IN TAIL-FLICK LATENCY OF NON-STRESSED AND STRESSED RATS
Ribeiro, S. M., Yang, P. B., Reyes-Vázquez, C., Swann, A. C., & Dafny, N. (2005) · International Journal of Neuroscience · doi:10.1080/00207450590956404 · Cited by 13 · see citing works
Chyzh, M., Кошурба, І. В., Marchenko, M. M., Hladkykh, F. V., & Belochkіna, I. (2023) · Modern medical technology · doi:10.34287/mmt.1(56).2023.9 · Cited by 12 · see citing works
Bai, X., Wang, C., Zhang, X., Feng, Y., & Zhang, X. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134868 · Cited by 12 · see citing works
Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats
Li, S.-G., Wang, J., & Luo, F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036767 · Cited by 10 · see citing works
The role of androgens on experimental pain sensitivity: a systemic review and meta-analysis
Wu-Chen, E., Banerjee, G., Requadt, E., Hunter, B., Baranski, T., Ross, W. T., & Nahman‐Averbuch, H. (2025) · PAIN Reports · doi:10.1097/pr9.0000000000001263 · Cited by 9 · see citing works
Kuba, T., Hunter, D. A., Zhou, L., Jenab, S., & Quiñones-Jenab, V. (2010) · PubMed · Cited by 4 · see citing works
Androgen levels and experimental pain sensitivity in healthy young adolescent girls
Banerjee, G., Brown, J. S., McMichael, A., Abdallah, A. B., Buday, S. K., Baranski, T., Haroutounian, S., Barch, D. M., AuBuchon, J., & Nahman‐Averbuch, H. (2025) · Pain · doi:10.1097/j.pain.0000000000003704 · Cited by 2 · see citing works
Денефіль, О. В., Druziuk, R. B., Medynskyi, M. I., Fedoniuk, L. Y., & Небесна, З. М. (2023) · Wiadomości Lekarskie · doi:10.36740/wlek202302105 · Cited by 2 · see citing works
Кошурба, І. В., Hladkykh, F. V., & Chyzh, M. (2023) · GASTROENTEROLOGY · doi:10.22141/2308-2097.57.2.2023.535 · Cited by 2 · see citing works
Melnik, A. V., Заічко, Н. В., Kachula, S., & Strutynska, O. B. (2017) · ScienceRise Medical Science · doi:10.15587/2519-4798.2017.97090 · Cited by 2 · see citing works
Jurić, M., Balog, M., Ivić, V., Bošković, M., Benzon, B., Racetin, A., Vukojević, K., Bočina, I., Kević, N., Restović, I., et al. (2021) · Neuropeptides · doi:10.1016/j.npep.2021.102126 · Cited by 2 · see citing works
Gender aspects of the pain syndrome
Ostrovska, K. (2019) · Pain medicine · doi:10.31636/pmjua.v4i1.5 · Cited by 1 · see citing works
Melnik, A. V. (2015) · Medicni perspektivi · doi:10.26641/2307-0404.2015.1.40233 · Cited by 1 · see citing works
Influence of sex hormones on DNA content and cystathionine-γ-lyase expression in rat myocardium
Melnik, A. V., Заічко, Н. В., Черешнюк, И. Л., Khodakіvskyi, О. А., & Haiduk, O. А. (2017) · Zaporozhye Medical Journal · doi:10.14739/2310-1210.2017.6.114693 · Cited by 1 · see citing works
Sensomotorik: abhängige Funktionen und Körperstrukturen
Laube, W. (2020) · Springer eBooks · doi:10.1007/978-3-662-60512-7_4 · Cited by 1 · see citing works
LaPrairie, J. L. (2022) · UPT. Syiah Kuala University Library (Syiah Kuala University) · doi:10.57709/1063878
Druziuk, R. B., & Денефіль, О. В. (2022) · Medical and Clinical Chemistry · doi:10.11603/mcch.2410-681x.2022.i2.13210
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Регеда, М., Вервега, Б. М., Stepas, Y., & Ярошенко, Т. Я. (2022) · Medical and Clinical Chemistry · doi:10.11603/mcch.2410-681x.2022.i2.13209
Druziuk, R. B., & Денефіль, О. В. (2022) · Bulletin Of Medical And Biological Research · doi:10.11603/bmbr.2706-6290.2022.4.13318
Druziuk, R. B., & Денефіль, О. В. (2022) · Medical and Clinical Chemistry · doi:10.11603/mcch.2410-681x.2022.i3.13375
Druziuk, R. B., & Денефіль, О. В. (2023) · Journal of Education Health and Sport · doi:10.12775/jehs.2023.14.01.006
Druziuk, R. B., & Денефіль, О. В. (2023) · Medical and Clinical Chemistry · doi:10.11603/mcch.2410-681x.2022.i4.13575
Druziuk, R. B., & Денефіль, О. В. (2022) · Шпитальна хірургія Журнал імені Л Я Ковальчука · doi:10.11603/2414-4533.2022.4.13607
Occurrence of Fatigue and Pain in Oncology Patients: Serie of Case Reports
Ramos, A. G. P., Dantas, J. B. D. L., Fortuna, T., Martins, G. B., Carrera, M., & Medrado, A. R. A. P. (2023) · Journal of Health Sciences · doi:10.17921/2447-8938.2023v25n2p72-77
Кошурба, І. В., Hladkykh, F. V., Chyzh, M., Marchenko, M. M., Koshurba, Y. V., & Hrishyn, V. B. (2023) · Clinical and Preventive Medicine · doi:10.31612/2616-4868.4(26).2023.15
Hladkykh, F. V., Кошурба, І. В., Komorovsky, R., Chyzh, M., Koshurba, Y. V., & Marchenko, M. M. (2023) · Scripta Medica · doi:10.5937/scriptamed54-46076
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Streett, M., Chandler, M., Luciani, L. L., Cetto, A. V., Kathol, J., & Painter, J. T. (2025) · Journal of Pain & Palliative Care Pharmacotherapy · doi:10.1080/15360288.2025.2599362
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Martin, L. J. (2026) · Neuromethods · doi:10.1007/978-1-0716-5312-8_9
Headaches, hormones, and transgender population: current evidence and knowledge gaps.
Grodzka, O., Szewczyk, A. K., Rogalska, M., Kukowka, A., Woźniak, P., Białecka, M. A., & Domitrz, I. (2026) · Archives of Medical Science · doi:10.5114/aoms/224765
- Authors
- ALOISI, A. M., CECCARELLI, I., & FIORENZANI, P.
- Affiliations
- University of Siena (IT)
- Corresponding author
- ALOISI, ANNA MARIA
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2003-12
- Volume
- 1007
- Issue
- 1
- Pages
- 232-237
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2093703392
- Cited by
- 66
- References
- 13
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 11 · 2022: 8 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- gonadectomy, gonadal hormones, testosterone, estradiol, corticosterone, formalin test, chronic pain, sex differences in pain, pain behavior, pain adaptation, male rats
- MeSH terms
- Animals, Corticosterone, Estradiol, Male, Orchiectomy, Pain Measurement, Testosterone, Rats, Wistar, Rats
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