Cytokine Antagonism Reduces Pain and Modulates Spinal Astrocytic Reactivity After Cervical Nerve Root Compression

Abstract

Relationships between nerve root compression, behavioral sensitivity, spinal cytokines, and glial reactivity are not fully defined for painful cervical nerve root compression. Spinal cytokines were quantified after mechanical root compression (10gf), root exposure to inflammatory chromic gut material (chr), the combination of both insults together (10gf + chr) or sham. TNFalpha and IL-1beta significantly increased at 1 h (p < 0.029). IL-1alpha was significantly increased over normal, sham and chr at 1 h following 10gf and over normal and sham after 10gf + chr (p < 0.048). By day 1, only IL-1beta after 10gf remained elevated over normal (p = 0.038). Accordingly, the soluble TNF receptor-1 (sTNFR1) and the IL-1 receptor antagonist (IL-1ra) were separately administered at early time points after each injury. With sTNFR1, behavioral sensitivity was significantly decreased for 7 days after both 10gf and 10gf + chr (p < 0.005). Treatment with IL-1ra significantly reduced sensitivity for 10gf + chr (p < 0.034) but not for 10gf. Sensitivity remained significantly elevated over sham at all time points (p < 0.044). Spinal astrocytic reactivity significantly decreased for both treatments after 10gf (p < 0.002); but, only IL-1ra following 10gf + chr significantly reduced astrocytic reactivity (p < 0.001). Early increases in spinal TNFalpha, IL-1beta, and IL-1alpha may induce pain, affect spinal astrocytic responses, and appear to have differential effects in mediating the behavioral hypersensitivity produced by different types of painful cervical radicular injuries.