Background & Aims

Rheumatoid arthritis (RA) is an inflammatory disorder characterized by edema and pain, as well as the destruction of synovial joints, which can lead to severe disability and premature death. Patients with RA experience intense, constant pain and stiffness in the joints that is often refractory to treatments, highlighting the urgent need for the development of novel pharmacological therapies. To address this, our group developed a synthetic peptide capable of reducing mechanical sensitivity in experimental inflammatory pain This peptide named QYP was based on investigations into mutations in the NTRK1 gene found in individuals with congenital insensitivity to pain with anhidrosis (CIPA) that decrease the interaction between TrkA and PLC?, leading to decreased NGF-induced signaling. And our aim is to evaluate the efficacy and mechanisms underlying QYP-induced analgesia in an RA model.

Methods

45 male mice (C57BL/6) were used, RA was induced by intra-articular injection (tibio-tarsal) of CFA (50 µL). After 14 days, the animals were evaluated in mechanical sensitivity tests (Von-Frey filaments) and thermal sensitivity tests (hot plate), HE is staining was also performed on samples from the tibio-tarsal joint to evaluate the inflammation caused by RA. Then treated with subcutaneous injection of QYP (1 mg/kg – 1 mg/ml) and behavioral tests were repeated after 1h and 3h.

Results

Data showed that there was a reduction in mechanical nociceptive threshold after CFA injection (p=0.0001) remaining reduced from the 7th to the 14th day, demonstrating the efficacy of the model in inducing RA, this data was confirmed through histological analysis, where through HE staining it was possible to observe the presence of a significant number of inflammatory infiltrates in the tibio-tarsal joint. Treatment with the QYP peptide was able to induce antinociceptive effect after 3h of treatment (p=0.0337) increasing mechanical thresholds but did not alter the thermal threshold of treated animals.

Conclusions

Thus, it was possible to observe the efficacy of QYP inducing analgesia in an experimental model of RA, suggesting therapeutic potential for inflammatory pain.

References

Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. doi:10.1002/art.27584

Croia C, Bursi R, Sutera D, Petrelli F, Alunno A, Puxeddu I. One year in review 2019: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2019;37(3):347-357.

Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003;423(6937):356-361. doi:10.1038/nature01661

Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358(9285):903-911. doi:10.1016/S0140-6736(01)06075-5

Moraes BC, Ribeiro-Filho HV, Roldão AP, et al. Structural analysis of TrkA mutations in patients with congenital insensitivity to pain reveals PLC? as an analgesic drug target. Sci Signal. 2022;15(731):eabm6046. doi:10.1126/scisignal.abm6046

Presenting Author

Gabriel Oliveira de Melo

Poster Authors

Gabriel Melo

Lead Author

Victoria da Silva Oliveira

University of Sao Paulo, IBS (Anatomy)

Lead Author

Deborah Schechtman

PhD.

Institute of Chemistry of University of São Paulo - Brazil

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Pain in Chronic/Inflammatory Diseases