P2RX7 and major depressive disorder: In a diabetic neuropathy model with comorbid depression, DHM alleviated both neuralgia and depressive symptoms by suppressing P2X7 receptor expression, thereby reducing ERK1/2 phosphorylation and proinflammatory cytokines (TNF-α, IL-1β) (Ge et al., 2019; Guan et al., 2019).