Neuropathic pain, inflammation and melatonin as supportive strategies
Neuropathic pain represents one of the most challenging conditions to treat in clinical practice. It is caused by a lesion or dysfunction of the peripheral or central somatosensory system and manifests with persistent symptoms such as burning sensations, electric shocks, allodynia and hyperalgesia.
These characteristics make neuropathic pain profoundly different from nociceptive pain and explain why standard pharmacological therapies are often only partially effective or limited by side effects.
The impact on quality of life is significant and affects sleep, mood, daily activities and therapeutic adherence.
Neuroinflammation and oxidative stress in pain chronicization
The reviewed article highlights how neuroinflammation and oxidative stress are central mechanisms in the onset and maintenance of neuropathic pain.
Following nerve injury, glial and immune cells release pro-inflammatory cytokines that increase neuronal excitability and promote both peripheral and central sensitization.
At the same time, excessive production of reactive oxygen species compromises mitochondrial function, alters cellular homeostasis and amplifies pain signal transmission.
These two processes fuel each other, creating a vicious cycle that promotes pain chronicization.
Nutrition and neuropathic pain: an emerging connection
In recent years, interest has grown in the role of nutrition as a modulating factor of inflammation and oxidative stress. Diets rich in refined sugars and saturated fats may promote a systemic pro-inflammatory state, whereas more balanced dietary patterns appear to be associated with better pain management.
Although the direct link between diet and neuropathic pain is not yet fully understood, available evidence suggests that nutrition can influence the biological mechanisms underlying neuropathy.
Gut–brain axis and microbiota in pain modulation
A particularly relevant element concerns the gut–brain axis, regulated by the intestinal microbiota. Alterations in microbial composition, often linked to unbalanced diets, can promote immune activation and systemic inflammation.
This inflammatory state may extend to the nervous system, contributing to neuroinflammation and sensitization of pain pathways. Modulating the microbiota through appropriate dietary choices therefore represents a potential complementary strategy in neuropathic pain management.
Melatonin as a key molecule in the neuro-nutritional approach
The core of the review focuses on the role of melatonin within a neuro-nutritional approach to neuropathic pain.
Traditionally known for regulating the sleep–wake rhythm, melatonin also exhibits antioxidant, anti-inflammatory and antinociceptive properties. It can directly neutralize free radicals and modulate antioxidant enzyme activity, contributing to the restoration of neuronal redox balance.
Moreover, through interaction with MT1 and MT2 receptors, melatonin may influence pain transmission at both central and peripheral levels.
Effects of melatonin on sleep and pain perception
Improving sleep quality represents a clinically relevant aspect of neuropathic pain management. Sleep disorders and chronic pain are closely interconnected and mutually reinforcing.
By normalizing the circadian rhythm, melatonin may indirectly contribute to reducing pain perception. This effect is particularly interesting within an integrated approach, as it targets a factor often overlooked but crucial for overall patient well-being.
Available clinical evidence and current limitations
Clinical evidence supporting the use of melatonin in neuropathic pain is still limited. However, studies conducted in chronic pain conditions such as fibromyalgia, migraine, and irritable bowel syndrome have shown improvements in both pain and sleep quality.
These findings suggest a potential role for melatonin as an adjunctive treatment, while also highlighting the need for larger and more specific clinical trials focused on neuropathic pain, with standardized protocols and clearly defined endpoints.
Dietary sources of melatonin and biological variability
Melatonin is also present in several plant-based foods, including fruits, vegetables, cereals and seeds. Consumption of these foods may help increase circulating melatonin levels, although dietary intake varies widely depending on factors such as ripeness, cultivation methods and food processing.
Additionally, oral bioavailability of melatonin shows high interindividual variability, making it difficult to precisely quantify the clinical effect of diet alone.
Other nutrients and bioactives in neuropathic pain management
Beyond melatonin, the review draws attention to other bioactive compounds, such as polyphenols, vitamins and minerals, which may contribute to modulation of inflammation and oxidative stress.
B vitamins, vitamin D, magnesium and zinc have been studied for their potential role in supporting nerve function and reducing neuronal hyperexcitability. These elements reinforce the concept of a multimodal and complementary approach alongside pharmacological therapy.
Therapeutic personalization and future perspectives
A key message of the article is the need to personalize the approach to neuropathic pain, taking into account age, sex, comorbidities and lifestyle.
The combination of pharmacotherapy, nutritional interventions and lifestyle modifications may represent an effective strategy to improve clinical outcomes. In this context, melatonin emerges as a promising candidate, but further clinical studies are essential to define its role within structured therapeutic protocols.
If your company is interested in creating or manufacturing a product for neuropathic pain:
Source: April 2025 – “Neuro-Nutritional Approach to Neuropathic Pain Management: A Critical Review”, MDPI
