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Data extraction focused on experimental models, key molecular targets, involvement of lactate metabolism or epigenetic regulation, and implications for DKD pathogenesis

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The loss of unmyelinated fibres may cause abnormal hyperactivity of second-order neurons of the brainstem.24 Given the suggestion that the continuous pain is a form of neuropathic pain, it may be possible to treat these patients with such pain modulators as antidepressants (amitriptyline, duloxetine) or antiepileptic drugs, among others, although most studies present low levels of evidence.25 Painful trigeminal neuropathy The ICHD-3 defines painful trigeminal neuropathy as pain in the territory of one or more branches of the trigeminal nerve with clinically detectable sensory deficits (hyperalgesia, allodynia, hypoaesthesia, hypoalgesia) presumably indicative of neural damage (Table 4).15 Trigeminal neuropathy is classified as being idiopathic or secondary to herpes zoster infection, trauma, or other disorders (Table 5)