Background & Aims

Osteoarthritis (OA) is one of the leading causes of chronic pain worldwide. Functional studies showed a critical role of descending facilitation, involving the rostral ventromedial medulla (RVM), in the establishment of pain chronicity. Our goal was to conduct an extensive analysis of the morpho-structural attributes of neuronal and glial cells in the RVM, along with an evaluation of glial activation, to increase our understanding of these contributing factors to osteoarthritis pain.

Methods

The kaolin/carrageenan model of experimental osteoarthritis (eOA) was induced in both male and female rats. Four weeks after induction, we evaluated changes in neuronal/glial cell density within the RVM through a stereological analysis. Additionally, glial activation was evaluated through the expression of GFAP and Iba1, astrocytic and microglial markers. Astrocyte proliferation and structural changes were further evaluated through immunofluorescence and a Sholl analysis, respectively.

Results

While no major differences were found between RVM structural and cellular characteristics of SHAM and K/C males, eOA led to an increase in the glia-to-neuron ratio in females. No differences in Iba1 immunoreactivity were found between experimental groups. However, females exhibited an increase in GFAP-positive cells and immunostained area after K/C induction, indicating an increase in astrogliosis, associated with an increase in mitotic activity and structural complexity.

Conclusions

Our findings indicate that RVM astrocytes respond differently to experimental osteoarthritis pain in males and females. By addressing the effects of biological sex and showing sex-dependent glial impact in the processing and modulation of pain, these data further contribute to highlighting the need to include female subjects in preclinical research.

References

Amorim, D., Fonseca-Rodrigues, D., David-Pereira, A., Costa, O., Lima, A.P., Nogueira, R., Cruz, R., Martins, A.S., Sousa, L., Oliveira, F., Pereira, H., Pirraco, R., Pertovaara, A., Almeida, A., Pinto-Ribeiro, F., 2023. Injection of kaolin/carrageenan in the rat knee joint induces progressive experimental knee osteoarthritis. Pain. https://doi.org/10.1097/j.pain.0000000000002954

Mo, S.-Y., Bai, S.-S., Xu, X.-X., Liu, Y., Fu, K.-Y., Sessle, B.J., Cao, Y., Xie, Q.-F., 2022. Astrocytes in the rostral ventromedial medulla contribute to the maintenance of oro-facial hyperalgesia induced by late removal of dental occlusal interference. Journal of Oral Rehabilitation 49, 207–218. https://doi.org/10.1111/joor.13211

Ji, R.-R., Berta, T., Nedergaard, M., 2013. Glia and pain: Is chronic pain a gliopathy? Pain 154, S10–S28. https://doi.org/10.1016/j.pain.2013.06.022

Presenting Author

Diana Fonseca-Rodrigues

Poster Authors

Diana Fonseca-Rodrigues, Msc

MSc

ICVS

Lead Author

E-mail

Inês Laranjeira

Life and Health Sciences Research Institute (ICVS)

Lead Author

E-mail

Luiz Falconi-Sobrinho

PhD

Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)

Lead Author

E-mail

Juliana Fernandes

University of Minho

Lead Author

E-mail

Beatriz Soares

Life and Health Sciences Research Institute (ICVS)

Lead Author

E-mail

Luísa Pinto

PhD

Life and Health Sciences Research Institute (ICVS)

Lead Author

E-mail

Filipa Pinto-Ribeiro

PhD

Life and Health Sciences Research Institute (ICVS)

Lead Author

E-mail

Topics

  • Mechanisms: Biological-Molecular and Cell Biology