Melatonin Could Be the Missing Key to Relieving Long COVID Pain and Inflammation
Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 09, 2025 1 week, 2 days, 10 hours, 35 minutes ago
Thailand Medical News: A growing number of COVID-19 survivors are finding themselves caught in a lingering web of health issues long after they recover from the initial infection. Chief among these is widespread pain syndrome (WPS)—a debilitating condition that affects the entire body with persistent aches, joint stiffness, and exhaustion. Now, researchers are turning their attention to an unexpected yet promising remedy—melatonin.
Melatonin Could Be the Missing Key to Relieving Long COVID Pain and Inflammation
The study, conducted by scientists from the Faculté de Médecine de Sousse at Université de Sousse in Tunisia and Prince Sultan University in Saudi Arabia, explores the potential of melatonin, the natural hormone best known for regulating sleep, as a treatment option for long COVID-related chronic pain and systemic inflammation. This
Thailand Medical News report dives into their findings and how melatonin could revolutionize treatment for countless people still struggling post-COVID.
Understanding Long COVID and Widespread Pain Syndrome
Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), affects more than 60% of individuals who have recovered from COVID-19. Its symptoms can persist for months or even years, including brain fog, heart issues, fatigue, sleep disturbances—and in many, chronic widespread musculoskeletal pain.
This chronic pain, known as widespread pain syndrome or WPS, affects up to 80% of long COVID sufferers. It is more than just random aches—it’s a daily burden that affects movement, mental health, and overall quality of life. The syndrome is believed to be driven by ongoing inflammation, oxidative stress, and a disruption in the body’s natural hormonal systems, especially melatonin production.
Melatonin’s Surprising Power
The review found that melatonin does much more than help with sleep. It possesses potent anti-inflammatory, antioxidant, and pain-relieving properties. These are exactly the kind of benefits needed to tackle long COVID’s complex damage pathways.
Melatonin was shown to reduce the production of harmful molecules like interleukin-6, TNF-alpha, and nitric oxide—all of which play key roles in the pain and inflammation that haunt long COVID patients. In fact, by calming down these inflammatory cascades, melatonin may help calm the nervous system and reduce pain signals throughout the body.
Moreover, melatonin influences important systems like serotonin and opioid receptors—natural pain-regulating pathways in the brain. It also boosts the body's antioxidant defenses and protects against damage from stress-induced molecules called free radicals.
Fighting Inflammaging and Rebalancing the System
One of the root causes of WPS in long COVID is a condition called “inflammaging,” a type of chronic low-grade infl
ammation usually seen in the elderly but now common in post-COVID patients. Melatonin helps counteract this state by restoring circadian rhythms and enhancing the immune response.
The researchers highlighted that melatonin supports healthy mitochondrial function (the energy factories of cells), balances immune signaling, and even improves sleep quality—which is crucial since poor sleep worsens pain perception. By restoring balance to this interconnected network, melatonin offers a rare multitarget therapy option.
Why This Matters Now
While standard painkillers can temporarily relieve WPS symptoms, they often come with serious side effects and fail to treat the root cause. Melatonin, being a natural substance already produced by the body, presents a much safer and holistic alternative.
Still, the study’s authors urge caution—long-term or high-dose melatonin use should be medically supervised, especially in vulnerable populations like pregnant or breastfeeding women.
Final Thoughts
This review shines a light on melatonin as a powerful yet overlooked tool in the fight against long COVID. With its unique ability to soothe inflammation, restore hormonal balance, and ease pain, melatonin could help millions of people recover both physically and mentally from the aftershocks of COVID-19. However, more clinical trials are urgently needed to determine the best dosages, safety profile, and long-term effects of melatonin in this specific context. Until then, researchers advocate prioritizing this compound in future long COVID treatment plans. Melatonin’s potential to ease suffering and restore normalcy makes it one of the most promising therapeutic candidates for widespread pain syndrome in long COVID sufferers.
The study findings were published in the peer reviewed journal: Frontiers in Pain Research
https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2025.1609095/full
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