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Phoneutria nigriventer Tx3-3 peptide toxin reduces fibromyalgia symptoms in mice
Claudia Pedron1, Flavia Tasmin Techera Antunes1, Isadora Nunes Rebelo2
1Graduate Program in Cellular and Molecular Biology for the Health Sciences, Lutheran University of Brazil, Canoas, Rio Grande do Sul 92425-900, Brazil.
Abstract:
Fibromyalgia is characterized by the amplification of central nervous system pain with concomitant fatigue, sleep, mood disorders, depression, and anxiety. It needs extensive pharmacological therapy. In the present study, Swiss mice were treated with reserpine (0.25 mg/kg, s.c.) over three consecutive days, in order to reproduce the pathogenic process of fibromyalgia. On day 4, the administrations of the Tx3-3 toxin produced significant antinociception in the mechanical allodynia (87.16% ±12.7%) and thermal hyperalgesia (49.46% ± 10.6%) tests when compared with the PBS group. The effects produced by the classical analgesics (duloxetine 30 mg/kg, pramipexole 1 mg/kg, and pregabalin 30 mg/kg, p.o., respectively) in both of the tests also demonstrated antinociception. The administrations were able to increase the levels of the biogenic amines (5-HTP and DE) in the brain. The treatments with pramipexole and pregabalin, but not duloxetine, decreased the immobility time in the FM-induced animals that were submitted to the forced swimming test; however, the Tx3-3 toxin (87.45% ± 4.3%) showed better results. Taken together, the data has provided novel evidence of the ability of the Tx3-3 toxin to reduce painful and depressive symptoms, indicating that it may have significant potential in the treatment of FM.
Insights
A novel toxin, Tx3-3, effectively reduced pain and depressive symptoms in a fibromyalgia mouse model. This toxin shows promise for treating fibromyalgia (FM) by targeting key pain and mood disorder pathways.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Fibromyalgia (FM) is a complex disorder characterized by amplified central nervous system pain, fatigue, sleep disturbances, and mood disorders like depression and anxiety.
- Current pharmacological treatments for FM are often extensive and may have limited efficacy.
- Reproducing the pathogenic process of FM in animal models is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the antinociceptive and antidepressant-like effects of the Tx3-3 toxin in a reserpine-induced fibromyalgia mouse model.
- To compare the efficacy of Tx3-3 with established analgesics such as duloxetine, pramipexole, and pregabalin.
- To explore the impact of Tx3-3 on biogenic amine levels in the brain.
Main Methods:
- Fibromyalgia was induced in Swiss mice using reserpine (0.25 mg/kg, s.c.) over three consecutive days.
- Tx3-3 toxin, PBS, duloxetine, pramipexole, and pregabalin were administered on day 4.
- Antinociception was assessed using mechanical allodynia and thermal hyperalgesia tests.
- Depressive-like behavior was evaluated using the forced swimming test.
- Brain biogenic amine levels (5-HTP and DE) were measured.
Main Results:
- Tx3-3 toxin demonstrated significant antinociception, reducing mechanical allodynia by 87.16% and thermal hyperalgesia by 49.46%.
- Classical analgesics also showed antinociceptive effects and increased biogenic amine levels.
- Tx3-3 toxin exhibited superior efficacy (87.45%) in reducing immobility time in the forced swimming test compared to pramipexole and pregabalin.
- Tx3-3 toxin increased brain levels of 5-HTP and DE.
Conclusions:
- The Tx3-3 toxin possesses significant antinociceptive and antidepressant-like properties in a preclinical fibromyalgia model.
- Tx3-3 toxin effectively alleviates both painful and depressive symptoms associated with fibromyalgia.
- Tx3-3 toxin represents a promising therapeutic candidate for the treatment of fibromyalgia.
