Neuropathic pain and diabetes: Focus on mechanisms and potential therapeutic strategies

Neuropathic pain is a challenging condition in clinical practice and a common complication in patients with diabetic neuropathy. In the last decade, several advances in the knowledge of the pathophysiological mechanisms of neuropathic pain have been achieved. Besides the mechanisms of peripheral and central sensitization involving axons, dorsal root ganglion, dorsal horn neurons, and descending modulatory pathways, the role of immune system and activated microglia and astrocytes, which can release chemokines, growth factors, nitric oxide, and nucleotides able to directly influence the neuronal electric activity, has been demonstrated. These complex mechanisms could partly explain the transition from the acute to the chronic phase of neuropathic pain and its maintenance over time. The ability of nerves to achieve a complete regeneration after injury can also influence persistence and intensity of neuropathic pain. Further important clues have come from studies demonstrating that neuropathic pain can be modulated by genetic background and that potential endogenous regulators of pain sensitivity and chronicity might be modulated by new drugs. These findings suggest that new strategies, with potential disease-modifying activity, might be available to treat chronic neuropathic pain in the near future.