Bioactive compounds for neuropathic pain: An update on preclinical studies and future perspectives

Among different types of chronic pain, neuropathic pain (NP), arising from damage to the nervous system, including peripheral fibers and central neurons, is notoriously difficult to treat and affects 7-10% of the general population. Currently available treatment options for NP are limited and opioid analgesics have severe side effects and can result in opioid use disorder. Recent studies have exhibited the role of dietary bioactive compounds in the mitigation of NP. Here, we assessed the effects of commonly consumed bioactive compounds (ginger, curcumin, omega-3 polyunsaturated fatty acids, epigallocatechin gallate, resveratrol, soy isoflavones, lycopene, and naringin) on NP and NP-related neuroinflammation. Cellular studies demonstrated that these bioactive compounds reduce inflammation via suppression of NF-κB and MAPK signaling pathways that regulate apoptosis/cell survival, antioxidant, and anti-inflammatory responses. Animal studies strongly suggest that these regularly consumed bioactive compounds have a pronounced anti-NP effect as shown by decreased mechanical allodynia, mechanical hyperalgesia, thermal hyperalgesia, and cold hyperalgesia. The proposed molecular mechanisms include (1) the enhancement of neuron survival, (2) the reduction of neuronal hyperexcitability by activation of antinociceptive cannabinoid 1 receptors and opioid receptors, (3) the suppression of sodium channel current, and (4) enhancing a potassium outward current in NP-affected animals, triggering a cascade of chemical changes within, and between neurons for pain relief. Human studies administered in this area have been limited. Future randomized controlled trials are warranted to confirm the findings of preclinical efficacies using bioactive compounds in patients with NP.