TNF-alpha contributes to spinal cord synaptic plasticity and inflammatory pain: Distinct role of TNF receptor subtypes 1 and 2

摘要: Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine. It generally believed that TNF-α exerts its effects primarily via TNF receptor subtype-1 (TNFR1). We investigated the distinct roles of TNFR1 and TNFR2 in spinal cord synaptic transmission inflammatory pain. Compared to wild-type (WT) mice, TNFR1- TNFR2-knockout (KO) mice exhibited normal heat sensitivity unaltered excitatory cord, as revealed by spontaneous postsynaptic currents lamina II neurons slices. However, hyperalgesia after intrathecal second-phase pain formalin test were reduced both TNFR2-KO mice. In particular, intraplantar injection complete Freund's adjuvant (CFA) was decreased early phase but later TNFR1-KO Consistently, CFA elicited transient increase mRNA levels on day 1. Notably, evoked drastic current frequency neurons, which abolished also increased N-methyl-d-aspartate (NMDA) this retained Finally, NMDA antagonist MK-801 prevented TNF-α. Our findings support central role regulating plasticity (central sensitization) TNFR2. data uncover unique mediating early-phase shown play critical sensitization, different phases