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Updated: Dec 8, 2025
Assessment of Knee Hyperalgesia in Mice using Pressure Application Measurement
Published on: June 13, 2025
Nociceptive mechanisms driving pain in a post-traumatic osteoarthritis mouse model
C J Alves1,2, M Couto3,4, D M Sousa3,4
1Neuro-Skeletal Circuits Group, Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal. cjmalves@ineb.up.pt.
Abstract:
In osteoarthritis (OA), pain is the dominant clinical symptom, yet the therapeutic approaches remain inadequate. The knowledge of the nociceptive mechanisms in OA, which will allow to develop effective therapies for OA pain, is of utmost need. In this study, we investigated the nociceptive mechanisms involved in post-traumatic OA pain, using the destabilization of the medial meniscus (DMM) mouse model. Our results revealed the development of peripheral pain sensitization, reflected by augmented mechanical allodynia. Along with the development of pain behaviour, we observed an increase in the expression of calcitonin gene-related peptide (CGRP) in both the sensory nerve fibers of the periosteum and the dorsal root ganglia. Interestingly, we also observed that other nociceptive mechanisms commonly described in non-traumatic OA phenotypes, such as infiltration of the synovium by immune cells, neuropathic mechanisms and also central sensitization were not present. Overall, our results suggest that CGRP in the sensory nervous system is underlying the peripheral sensitization observed after traumatic knee injury in the DMM model, highlighting the CGRP as a putative therapeutic target to treat pain in post-traumatic OA. Moreover, our findings suggest that the nociceptive mechanisms involved in driving pain in post-traumatic OA are considerably different from those in non-traumatic OA.
Insights
Investigating post-traumatic osteoarthritis (OA) pain mechanisms in mice revealed peripheral pain sensitization. Calcitonin gene-related peptide (CGRP) in sensory nerves drives this sensitization, suggesting it as a therapeutic target for OA pain.
Area of Science:
- Neuroscience
- Orthopedics
- Pain Research
Background:
- Osteoarthritis (OA) pain significantly impacts quality of life, yet effective treatments are lacking.
- Understanding the specific pain mechanisms in post-traumatic OA is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the underlying nociceptive mechanisms in a mouse model of post-traumatic OA.
- To identify potential therapeutic targets for managing pain in post-traumatic OA.
Main Methods:
- Utilized the destabilization of the medial meniscus (DMM) mouse model to induce post-traumatic OA.
- Assessed pain behavior, specifically mechanical allodynia.
- Measured the expression of calcitonin gene-related peptide (CGRP) in sensory nerve fibers and dorsal root ganglia.
Main Results:
- The DMM model exhibited peripheral pain sensitization, evidenced by increased mechanical allodynia.
- Calcitonin gene-related peptide (CGRP) expression was elevated in sensory nerves of the periosteum and dorsal root ganglia.
- Key OA pain mechanisms like immune cell infiltration, neuropathic changes, and central sensitization were notably absent.
Conclusions:
- Calcitonin gene-related peptide (CGRP) in the sensory nervous system is a key driver of peripheral sensitization in post-traumatic OA.
- CGRP represents a promising therapeutic target for treating pain associated with post-traumatic OA.
- Nociceptive mechanisms in post-traumatic OA differ significantly from those in non-traumatic OA phenotypes.
