Association of the Serotonin and Kynurenine Pathways as Possible Therapeutic Targets to Modulate Pain in Patients with Fibromyalgia
Abstract
:1. Introduction
2. Physiopathology of Fibromyalgia
3. Tryptophan and Fibromyalgia
4. Role of Serotonin Receptors in Pain in Patients with Fibromyalgia
4.1. 5-HT1 Receptor
4.2. 5-HT2A Receptor
4.3. 5-HT3 Receptor
4.4. Selective Serotonin Reuptake Inhibitors
- -
- **NCT01288807**: Conducted in eight adult female patients, this open study assessed milnacipran at 200 mg daily over 12 weeks but did not report no analgesic effect.
- -
- **NCT00314249**: This large-scale, multicenter, double-blind, placebo-controlled study involving 1025 adult FM patients evaluated milnacipran at 100 mg per day for 12 weeks and reported a positive analgesic effect.
- -
- **NCT00115804**: A pilot trial in six patients with juvenile primary fibromyalgia syndrome treated with fluoxetine (10 to 60 mg daily for 12 weeks) reported a decrease in the analgesic effect.
- -
- **NCT01237587**: In 184 patients with juvenile primary fibromyalgia syndrome, this quadruple-blind, placebo-controlled study assessed duloxetine (30/60 mg/day for 23 weeks) and found a positive analgesic effect.
- -
- **NCT01552057**: A randomized, double-blind, placebo-controlled trial with 393 adult patients with FM that evaluated duloxetine at 60 mg/day for 15 weeks and reported a positive outcome.
- -
- **NCT00797797**: This study combined milnacipran (100 mg/day) and pregabalin (300 or 450 mg/day) over 11 weeks in 364 adult FM patients and reported a positive analgesic effect.
- -
- **NCT01108731** and **NCT01173055**: These studies, which assessed milnacipran at lower doses (12.5 mg for 9 weeks and 200 mg/day, respectively), reported no analgesic effects in their small cohorts.
- -
- **NCT00673452**: A large trial of 530 adult FM patients evaluating duloxetine (60–120 mg/day for 12 weeks), which revealed a positive analgesic effect.
- -
- **NCT01077375**: This multicenter study assessed milnacipran (100 to 200 mg/day for 10 weeks) in 120 adult FM patients and reported a positive analgesic effect.
- -
- **NCT01829243**: Focusing on older adult FM patients (26 participants), this study assessed milnacipran at various doses (12.5–200 mg/day) and found no analgesic effect.
- -
- **NCT00965081**: A quadruple-blind study with 308 adult FM patients evaluated duloxetine at 30 mg/day for 12 weeks and reported a positive effect.
- -
- **NCT01038323**: Milnacipran at 12.5 mg/day for 21 weeks was administered to 58 adult FM patients, and a positive analgesic effect was detected.
5. Role of Kynurenine in Pain in Fibromyalgia
6. Discussion
7. Conclusions
8. Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Registry Number | Patients | Study Design | Medication | Dose | Analgesic Effect |
---|---|---|---|---|---|
NCT01288807 | 8 adult female patients with fibromyalgia | Single group assignment, open study | Milnacipran | 200 mg/day for 12 weeks | NO |
NCT00314249 | 1025 adult patients with fibromyalgia | Randomized, multicenter, double-blind, placebo controlled | Milnacipran | 100 mg/day for 12 weeks | YES |
NCT01173055 | 22 adult female patients with fibromyalgia | Randomized, double-blind, two-way placebo controlled | Milnacipran | 200 mg/day for 6 weeks | NO |
NCT01108731 | 37 adult fibromyalgia patients | Quadruple-blind, randomized, placebo controlled | Milnacipran | 12.5 mg/day for 9 weeks | NO |
NCT01077375 | 120 adult patients with fibromyalgia | Multicenter, randomized, double-blind, placebo controlled | Milnacipran | 100 to 200 mg/day for 10 weeks | YES |
NCT01829243 | 26 older adult patients with fibromyalgia | Randomized, double-blind, two-way placebo controlled | Milnacipran | 12.5 mg 200 mg/day for 13 weeks | NO |
NCT01038323 | 58 adult fibromyalgia patients | Triple-blind, randomized, 3-way placebo controlled | Milnacipran | 12.5 mg/day for 21 weeks | YES |
NCT00797797 | 364 adult fibromyalgia patients | Multicenter, randomized, open-label, placebo controlled study | Milnacipran and pregabalin | Milnacipran 100 mg/day and pregabalin 300 or 450 mg/day for 11 weeks | YES |
NCT00673452 | 530 adult fibromyalgia patients | Quadruple-blind, randomized, two-way placebo controlled | Duloxetine | 60–120 mg/day for 12 weeks | YES |
NCT01237587 | 184 patients with juvenile primary fibromyalgia syndrome | Multicenter, quadruple-blind, randomized, placebo-controlled, 2-way crossover | Duloxetine | 30/60 mg/day for 23 weeks | YES |
NCT00965081 | 308 adult fibromyalgia patients | Quadruple-blind, randomized, two-way placebo controlled | Duloxetine | 30 mg/day for 12 weeks | YES |
NCT01552057 | 393 adult fibromyalgia patients | Randomized, double-blind, placebo controlled | Duloxetine | 60 mg/day for 15 weeks | YES |
NCT00115804 | 6 patients with juvenile primary fibromyalgia syndrome | Pilot trial, single group assignment, open study | Fluoxetine | 10 to 60 mg/day for 12 weeks | LOWER |
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Alfaro-Rodríguez, A.; Reyes-Long, S.; Roldan-Valadez, E.; González-Torres, M.; Bonilla-Jaime, H.; Bandala, C.; Avila-Luna, A.; Bueno-Nava, A.; Cabrera-Ruiz, E.; Sanchez-Aparicio, P.; et al. Association of the Serotonin and Kynurenine Pathways as Possible Therapeutic Targets to Modulate Pain in Patients with Fibromyalgia. Pharmaceuticals 2024, 17, 1205. https://doi.org/10.3390/ph17091205
Alfaro-Rodríguez A, Reyes-Long S, Roldan-Valadez E, González-Torres M, Bonilla-Jaime H, Bandala C, Avila-Luna A, Bueno-Nava A, Cabrera-Ruiz E, Sanchez-Aparicio P, et al. Association of the Serotonin and Kynurenine Pathways as Possible Therapeutic Targets to Modulate Pain in Patients with Fibromyalgia. Pharmaceuticals. 2024; 17(9):1205. https://doi.org/10.3390/ph17091205
Chicago/Turabian StyleAlfaro-Rodríguez, Alfonso, Samuel Reyes-Long, Ernesto Roldan-Valadez, Maykel González-Torres, Herlinda Bonilla-Jaime, Cindy Bandala, Alberto Avila-Luna, Antonio Bueno-Nava, Elizabeth Cabrera-Ruiz, Pedro Sanchez-Aparicio, and et al. 2024. "Association of the Serotonin and Kynurenine Pathways as Possible Therapeutic Targets to Modulate Pain in Patients with Fibromyalgia" Pharmaceuticals 17, no. 9: 1205. https://doi.org/10.3390/ph17091205