Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation

Intra-RVM rTNF-α and rIL-1β enhance pNR1 levels and produce descending pain facilitation in normal rats. A, Microinjection of rTNF-α (120 fmol) and rIL-1β (120 fmol) into the RVM enhances expression of pNR1ser896 in the RVM tissue compared with baseline levels in naive rats (p < 0.05; n = 4 per group). Pretreatment of an NMDAR channel blocker MK801 (+) (n = 4) completely prevents rTNF-α- and rIL-1β-induced increase in pNR1 compared with vehicle treatment (−). RVM tissues are collected at 2 h after microinjection of the recombinant agents into the RVM. B, Mechanical sensitivity of the skin is assessed after microinjection of rTNF-α. The behavioral hyperalgesia and allodynia develops and lasts for 4 h after microinjection of rTNF-α (120 fmol) as indicated by a reduction of EF₅₀ values (p < 0.05). Pretreatment of MK801 (10 pmol) significantly abolishes rTNF-α-produced mechanical hypersensitivity compared with vehicle plus rTNF-α. C, Microinjection of rIL-1β (120 fmol) results in a significant reduction of EF₅₀ values for 2 h (p < 0.05), which is prevented by pretreatment with MK801. *p < 0.05, rTNF-α or rIL-1β versus vehicle injection. Error bars indicate SEM.