Preclinical as well as human studies indicate that
melatonin is essential for a physiological sleep state, promotes
analgesia and is involved in immunometabolic signaling by regulating neuroinflammatory pathways. Experimental and clinical neuromodulation studies for
chronic pain treatment suggest that neurostimulation
therapies such as
spinal cord stimulation,
vagus nerve stimulation and dorsal root ganglion stimulation have an impact on circulating inflammatory mediators in blood, cerebrospinal fluid and saliva. Herein, we provide an overview of current literature relevant for the shared pathways of sleep,
pain and immunometabolism and elaborate the impact of
melatonin on the crossroad of sleep,
chronic pain and immunometabolism. Furthermore, we discuss the potential of
melatonin as an adjunct to neurostimulation
therapies. In this narrative review, we addressed these questions using the following search terms:
melatonin, sleep, immunometabolism,
obesity,
chronic pain, neuromodulation, neurostimulation,
neuroinflammation, molecular inflammatory phenotyping. So far, the majority of the published literature is derived from experimental studies and studies specifically assessing these relationships in context to neurostimulation are sparse. Thus, the adjunct potential of
melatonin in clinical neurostimulation has not been evaluated under the umbrella of randomized-controlled trials and deserves increased attention as
melatonin interacts and shares pathways relevant for noninvasive and invasive neurostimulation
therapies.