Background & Aims
There exists a significant knowledge gap concerning the intricate relationship between chronic pain and psychiatric disorders, leading to a deficiency in effective therapeutic solutions 1,2. While chronic pain is widespread across medical conditions, and the epidemiological link with psychiatric disorders is established, there is an urgent need for exploration within preclinical research to better comprehend the mechanisms of this comorbidity 3. However, the diversity of approaches, methodologies, and experimental designs in experimental behavioral assessments within preclinical pain research occasionally impede reproducibility and translatability 4,5. In this context, our systematic review and meta-analysis aimed to clarify the modulatory influence of variables such as sex and species, among others, on anxiety-like and depressive-like behavior in neuropathic pain animal models.
Methods
Following stablished guidelines and registration on PROSPERO (CRD42022366275)6,7, we initiated searches across EMBASE, Scopus, and Web of Science databases to identify studies involving rodents subjected to mechanically-induced neuropathic pain surgeries, subsequently undergoing assessments for anxiety or depressive-like behaviors. A preliminary peer-blinded review was conducted for titles and abstracts using RAYYAN, followed by a full-text examination to identify studies meeting the inclusion criteria. One hundred and twenty-nine studies, which evaluated performance in the elevated maze tests or forced swimming test, were included in our meta-analysis.
Results
Neuropathic pain significantly reduced both time in open arms in the elevated maze test and passive stress coping in the forced swimming test. Subgroup analysis revealed sex differences in this effect for both assays, wherein females did not exhibit the behavioral alterations observed in males. Interestingly, meta-regression analysis unveiled an association between the width of the surgical suture and exploratory behavior.
Conclusions
The present meta-analysis showed how neuropathic pain significantly impact anxiety and depressive-like behaviors in rodents. Drawing from the evidence presented, we also suggest that forthcoming studies should prioritize investigating the impact of sex differences on behavioral outcomes, as rodent females do not appear to develop the same behavioral phenotype as males.
References
1.Knaster, P., Karlsson, H., Estlander, A.-M. & Kalso, E. Psychiatric disorders as assessed with SCID in chronic pain patients: the anxiety disorders precede the onset of pain. Gen. Hosp. Psychiatry 34, 46–52 (2012).
2.Lerman, S. F., Rudich, Z., Brill, S., Shalev, H. & Shahar, G. Longitudinal Associations Between Depression, Anxiety, Pain, and Pain-Related Disability in Chronic Pain Patients. Psychosom. Med. 77, 333 (2015).
3.Bravo, L., Llorca-Torralba, M., Suárez-Pereira, I. & Berrocoso, E. Pain in neuropsychiatry: Insights from animal models. Neurosci. Biobehav. Rev. 115, 96–115 (2020).
4.Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests. vol. 42 (Humana Press, Totowa, NJ, 2009).
5.Ravenelle, R., Santolucito, H. B., Byrnes, E. M., Byrnes, J. J. & Donaldson, S. T. Housing environment modulates physiological and behavioral responses to anxiogenic stimuli in trait anxiety male rats. Neuroscience 270, 76–87 (2014).
6.Hooijmans, C. R. et al. SYRCLE’s risk of bias tool for animal studies. BMC Med. Res. Methodol. 14, 43 (2014).
7.Page, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372, n71 (2021).
Presenting Author
Tomas de la Rosa Macías
Poster Authors
Tomás de la Rosa Macías
PhD
Universidad de Cádiz
Lead Author
Meritxell Llorca-Torralba Ph.D.
Cell Biology department, University of Cádiz - CIBERSAM
Lead Author
Adrian Martinez-Cortes
Psychology department, University of Cádiz - CIBERSAM
Lead Author
Cristina Romero-Lopez-Alberca
Psychology department, University of Cádiz - CIBERSAM
Lead Author
Esther Berrocoso
Neuroscience department, University of Cádiz - CIBERSAM
Lead Author
Topics
- Models: Chronic Pain - Neuropathic