Background & Aims

Chronic pain is a complex health burden which is usually associated to other pathologies such as anxiety, depression, drug abuse disorders and cognitive impairments. Interestingly, prefrontal cortex (PFC) and nucleus accumbens (NAc) plays a role in both pain processing and its comorbidities1. Clinic evidence suggest that alterations related to astrocytes and glutamate homeostasis are associated with pain chronification and the development of its comorbidities2, even though the role of this in the PFC to NAc projection is not very clear yet. Neuroplastic events in this projection can be potentially implicated in cognitive and behavioral alterations induced by the presence of pain that can ultimately promote the former mentioned pain comorbidities. Thus, our aim is to study how inflammatory pain alters astrocytes and the glutamatergic system in PFC and NAc from male and female rats.

Methods

Male and female Sprague Dawley rats (n=8/group) were injected in the hindpaw with the Complete Freund Adjuvant (CFA) to produce inflammatory pain for one week. The levels of expression of markers related to astrocytes’ density and function (GFAP, xCT and GLT-1) and the ones related to glutamatergic system and neuroplasticity (EGR1, mGluR2 and NMDA receptors) were analysed in PFC and NAc using immunohistochemistry and western blot.

Results

Inflammatory pain induces an increase in GFAP and xCT expression in selected PFC subregions. Interestingly, baseline expression of certain receptors differs between male and female rats. Specifically, GLT-1 levels in the PFC and xCT levels in the NAc are elevated in female rats, while mGluR2 expression is heightened in male rats within the NAc. Furthermore, inflammatory pain induced alterations in the NMDA receptor NR2A and NR2B subunits, indicating neuroplastic adaptations that may impact cognitive and behavioral responses associated with inflammatory pain.

Conclusions

In summary, our findings demonstrate that inflammatory pain induces significant alterations in astrocyte density and function within the prefrontal cortex (PFC) and nucleus accumbens (NAc), accompanied by notable neuroplastic changes. The observed alterations in astrocyte function and glutamatergic signaling pathways offer valuable insights into the mechanisms underlying pain chronification and its comorbidities.

References

1 Harris, H. N., & Peng, Y. B. (2020). Evidence and explanation for the involvement of the nucleus accumbens in pain processing. Neural regeneration research, 15(4), 597–605. https://doi.org/10.4103/1673-5374.266909
2 Lu, H. J., & Gao, Y. J. (2023). Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms. Neuroscience bulletin, 39(3), 425–439. https://doi.org/10.1007/s12264-022-00961-3

Presenting Author

Lucia Hipólito

Poster Authors

Lucia Hipólito

PhD

University of Valencia ESQ4618002B

Lead Author

E-mail

Paula Andrés-Herrera

PhD student

University of Valencia

Lead Author

E-mail

Javier Cuitavi

PhD

University of Valencia

Lead Author

E-mail

María De Jorge

University of Valencia

Lead Author

E-mail

Rocío Pérez-Ratón

University of Valencia

Lead Author

E-mail

María Ros-Ramírez de Arellano

University of Valencia

Lead Author

E-mail

Ana Polache

University of Valencia

Lead Author

E-mail

Topics

  • Mechanisms: Biological-Systems (Physiology/Anatomy)

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