Skip to main content
Log in

Sex-dependent differences in parameters of long-term pain caused by inflammatory focus in prenatally stressed newborn rats

  • Comparative and Ontogenic Physiology
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

In experiments on the 7-day old female and male Long-Evans rat pups, for the first time, there was studied effect of prenatal (immobilization) stress on dynamics of nociceptive behavioral response caused by an inflammatory focus. The nociceptive sensitivity was evaluated for 1 h by the number of the flexion-shaking patterns organized at the spinal level in response to injection of formalin (10%, 10 μl) to the posterior leg sole. Control rat pups were not submitted to any prenatal stress; in these animals the response in the formalin test was found to be represented by one phase. It the prenatally stressed rat pups the studied patterns were organized into two phases characteristic of the definitive type of response. At the period between them (during interphase), the nociceptive behavior was absent. At the second, tonic phase the number of flexion-shakings in the prenatally stressed males was statistically significantly higher than in the prenatally stressed females, which indicates a sensitization of the neurons involved in the tonic pain chains in male individuals. Thus, the data obtained on prenatally stressed animals confirm the previous data about immaturity of the mechanisms mediating the second phase of response in the formalin test in the 7-day old rat pups. An important fact is revealed which indicates that in the prenatally stressed rat pups of the same age the second phase of response is already obvious. Mechanisms underlying the behavioral response caused by the inflammatory focus in the formalin test in the one-week old stressed rat pups are characterized by sexual dimorphism: the pain sensitivity in males at the second phase of response is statistically significantly higher than in females.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rode, V., Okava, T., Shtal, F., Getz, F., Tenies, R., Takeshita, S., Arakava, S., Kambegava, A., Arai, K., Okinaga, S., and Derner, G., Changes of the Neuroendocrine System in Rat Fetuses in Acute Stress in the End of Pregnancy, Ontogeneticheskie i genetiko-evolyutsionnye aspekty neiroendokrinnoi regulyatsii stressa (Ontogenetic and Genetic-Evolutional Aspects of Neuroendocrine Regulation of Stress), Naumenko, E.V. and Popova, N.K., Eds., Novosibirsk: 1990, pp. 40–55.

  2. Takahashi, L.K., Turner, J.C., and Kalin, N.N., Prenatal Stress Alters Brain Catecholaminergic Activity and Potentiates Stress-Induced Behavior in Adult Rats, Brain Res., 1992, vol. 574, pp. 131–137.

    Article  PubMed  CAS  Google Scholar 

  3. Resnikov, A.G., Pishak, V.P., Nosenko, N.D., Tkachuk, S.S., and Myslitskii, V.F., Prenatal’nyi stress i neiroendokrinnaya patologiya (Prenatal Stress and Neuroendocrine Pathology), Chernovtsy, 2004, 351 pp.

  4. Weiherg, L.A.M. and Seckl, L.R., Prenatal Stress, Glucocorticoids and the Programming of the Brain, J. Neuroendocrinol., 2001, vol. 13, pp. 113–128.

    Article  Google Scholar 

  5. Huizink, A.C., Mulder, E.J., and Buitelaar, J.K., Prenatal Stress and Risk for Psychopathology: Specific Effects or Induction of General Susceptibility?, Psychol. Bull., 2004, vol. 130, pp. 115–142.

    Article  PubMed  Google Scholar 

  6. Weinstock, M., Alterations Induced by Gestational Stress in Brain Morphology and Behaviour of the Offspring, Progr. Neurobiol., 2001, vol. 65, pp. 427–451.

    Article  CAS  Google Scholar 

  7. Weinstock, M., The Potential Influence of Maternal Stress Hormones on Development and Mental Health of the Offspring, Brain Behav. Immun., 2005, vol. 135, pp. 296–308.

    Article  CAS  Google Scholar 

  8. Szuran, T., Zimmerman, E., Pliska, V., Pfister, H.P., and Welzl, H., Prenatal Stress Effects on Exploratory Activity and Stress Induced Analgesia in Rats, Dev. Psychobiol., 1991, vol. 24, no. 5, pp. 361–372.

    Article  PubMed  CAS  Google Scholar 

  9. Kofman, O., The Role of Prenatal Stress in the Etiology of Developmental Behavioural Disorders, Neurosci. Biobehav. Rev., 2002, vol. 26, pp. 457–470.

    Article  PubMed  CAS  Google Scholar 

  10. Sternberg, W.F., Effects of Gestational Stress and Neonatal Handling on Pain, Analgesia, and Stress Behavior of Adult Mice, Physiol. Behav., 2003, vol. 78, pp. 375–383.

    Article  PubMed  CAS  Google Scholar 

  11. Knackstedt, M.K., Hamelmann, E., and Arck, P.C., Mothers in Stress: Consequences for the Offspring, Am. J. Reprod. Immunol., 2005, vol. 54, pp. 63–69.

    Article  PubMed  CAS  Google Scholar 

  12. Butkevich, I.P. and Vershinina, E.A., Prenatal Stress Alters Time Characteristics and Intensity of Formalin-Induced Pain Responses in Juvenile Rats, Brain Res., 2001, vol. 915, pp. 88–93.

    Article  PubMed  CAS  Google Scholar 

  13. Butkevich, I.P. and Vershinina, E.A., Maternal Stress Differently Alters Nociceptive Behaviors in the Formalin Test in Adult Female and Male Rats, Brain Res., 2003, vol. 961, pp. 159–165.

    Article  PubMed  CAS  Google Scholar 

  14. Dubuisson, D. and Dennis, S.G., The Formation Test: A Quantitative Study of the Analgesic Effects of Morphine, Meperidine, and Brain Stimulation in Rats and Cats, Pain, 1977, vol. 4, pp. 161–174.

    Article  PubMed  CAS  Google Scholar 

  15. Wheeler-Aceto, H. and Cowan, A., Standardization of the Rat Paw Formalin Test for the Evaluation of Analgesics, Psychopharmacol., 1991, vol. 104, pp. 35–44.

    Article  CAS  Google Scholar 

  16. Barr, G.A., Maturation of the Biphasic Behavioral and Heart Rate Response in the Formalin Test, Pharmacol. Biochem. Behav., 1998, vol. 60, pp. 329–335.

    Article  PubMed  CAS  Google Scholar 

  17. Matties, K. and Franklin, K.B.J., Formalin Pain Is Expressed by Decelerated Rats but not Attenuated by Morphine, Pain, 1992, vol. 51, pp. 199–206.

    Article  Google Scholar 

  18. Guy, E.R. and Abbott, F.V., The Behavioral Response to Formalin in Preweanling Rats, Pain, 1992, vol. 51, pp. 81–90.

    Article  PubMed  CAS  Google Scholar 

  19. Aloisi, A.M., Role of the Limbic System in Sex, Gender, and Pain, Proceedings of the 9th World Congress on Pain, Devor, M., Rowbotham, M.C., and Wiesenfeld-Hallin, Z., Eds., Seattle: IASP, 2000, pp. 567–579.

    Google Scholar 

  20. Fillingim, R.B. and Ness, T.J., Sex-Related Hormonal Influences on Pain and Analgesic Responses, Neurosci. Biobehav. Rev., 2000, vol. 24, pp. 485–501.

    Article  PubMed  CAS  Google Scholar 

  21. Craft, R.M., Mogil, J.S., and Aloisi, A.M., Sex Differences in Pain and Analgesia: The Role of Gonadal Hormones, Eur. J. Pain, 2004, vol. 8, pp. 397–411.

    Article  PubMed  CAS  Google Scholar 

  22. Bradshaw, H., Miller, J., Ling, Q., Malsnee, K., and Ruda, M.A., Sex Differences and Phases of the Estrous Cycle Alter the Response of Spinal Cord Dynorphin Neurons to Peripheral Inflammation and Hyperalgesia, Pain, 2000, vol. 85, pp. 93–99.

    Article  PubMed  CAS  Google Scholar 

  23. Gaumond, I., Arsenault, P., and Marchand, S., The Role of Sex Hormones on Formalin-Induced Nociceptive Responses, Brain Res., 2002, vol. 958, pp. 139–145.

    Article  PubMed  CAS  Google Scholar 

  24. Kuba, T., Kemen, L.M., and Quinones-Jenab, V., Estradiol Administration Mediates the Inflammatory Response to Formalin in Female Rats, Brain Res., 2005, vol. 1047, pp. 119–122.

    Article  PubMed  CAS  Google Scholar 

  25. Aloisi, A.M., Ceccarelli, I., Fiorenzani, P., Padova, A.M., and de Massafra, C., Testosterone Affects Formalin-Induced Responses Differently in Male and Female Rats, Neurosci. Lett., 2004, vol. 361, pp. 262–264.

    Article  PubMed  CAS  Google Scholar 

  26. Ward, I.L. and Weisz, J., Differential Effects of Maternal Stress on Circulating Levels of Corticosterone, Progesterone, and Testosterone in Male and Female Rat Fetuses and Their Mothers, Endocrinol., 1984, vol. 114, pp. 1635–1644.

    Article  CAS  Google Scholar 

  27. Murase, T., The Effects of Maternal Stress on the Aromatase Activity in the Perinatal Rat Brain, Nippon Naibunpi Gakkai Zasshi., 1994, vol. 70, pp. 95–104.

    PubMed  CAS  Google Scholar 

  28. Ordyan, N.E., Neuroendocrine Mechanisms of Effect of Maternal Stress on the Offspring Adaptive Functions and Behavior, Osnovy neiroendokrinologii (Grounds of Neuroendocrinology), Shalyapina, V.G. and Shabanova, P.D., Eds., S-Petersburg, 2005, pp. 307–336.

  29. Ordyan, N.E. and Pivina, S.G., Effect of Prenatal Stress on Activity of the Enzyme Participating in Neurosteroid Synthesis at the “Critical Period” of Sex Differentiation of the Male Rat Brain, Sechenov Ross. Fiziol. Zh. RAN, 2004, vol. 90, pp. 1255–1261.

    Google Scholar 

  30. Committee for Research and Ethical Issue of the IASP. Ethical Standards for Investigations of Experimental Pain in Animals, Pain, 1983, vol. 16, pp. 109–110.

    Article  Google Scholar 

  31. Dickenson, A.H. and Sullivan, A.F., Peripheral Origins and Central Modulation of Subcutaneous Formalin-Induced Activity of Rat Dorsal Horn Neurons, Neurosci. Lett., 1987, vol. 83, pp. 207–211.

    Article  PubMed  CAS  Google Scholar 

  32. Chapman, V. and Dickenson, A.H., Time-Related Roles of Excitatory Amino Acid Receptors during Persistent Noxiously Evoked Responses of the Rat, Brain Res., 1995, vol. 703, pp. 207–211.

    Article  Google Scholar 

  33. Carlton, S.M. and Cogeshall, R.I., Inflammation-Induced Changes in Peripheral Glutamate Receptor Populations, Brain Res., 1999, vol. 820, pp. 63–70.

    Article  PubMed  CAS  Google Scholar 

  34. Narsinghani, V. and Anand, K.J.S., Development Neurobiology of Pain in Neonatal Rats, Lab. Animal, 2000, vol. 29, pp. 27–39.

    PubMed  Google Scholar 

  35. Jakowec, M.W., Fox, A.J., Martin, L.J., and Kalb, R.G., Quantitative and Qualitative Changes in AMPA Receptor Expression during Spinal Cord Development, Neurosci., 1995, vol. 67, pp. 893–907.

    Article  CAS  Google Scholar 

  36. Butkevich, I.P., Mikhailenko, V.A., Vershinina, E.A., Khozhai, I., Grigor’ev, I.P., and Otellin, V.A., Reduced Serotonin Synthesis during Early Embryogeny Changes Effects of Subsequent Prenatal Stress on Persistent Pain in the Formalin Test in Adult Male and Female Rats, Brain Res., 2005, vol. 1042, pp. 144–159.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Original Russian Text © I. P. Butkevich, G. A. Barr, and E. A. Vershinina, 2007, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2007, Vol. 43, No. 1, pp. 54–59.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Butkevich, I.P., Barr, G.A. & Vershinina, E.A. Sex-dependent differences in parameters of long-term pain caused by inflammatory focus in prenatally stressed newborn rats. J Evol Biochem Phys 43, 61–68 (2007). https://doi.org/10.1134/S0022093007010061

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093007010061

Key words

Navigation