INCREASE OF INTERLEUKIN-6 MESSENGER-RNA IN THE SPINAL-CORD FOLLOWING PERIPHERAL-NERVE INJURY IN THE RAT - POTENTIAL ROLE OF IL-6 IN NEUROPATHIC PAIN

Interleukin-6 (IL-6) is a multifunctional cytokine whose actions inclu de modulation of proliferation, differentiation, and maturation of hem apoietic progenitors and other cell lineages; growth regulation of cer tain carcinoma cell lines; and control of cellular metabolic activitie s. Initially described in terms of its activities in the immune system and inflammation, accumulating evidence supports an essential role of IL-6 in the development, differentiation, regeneration and degenerati on of neurons in the peripheral and central nervous system. We have pr eviously demonstrated that immunoreactive-like IL-6 protein is signifi cantly elevated in the spinal cord in response to peripheral nerve inj ury that results in neuropathic pain behaviors in the rat. In the curr ent study, our objective was to determine if the source of IL-6 protei n was endogenous to the central nervous system by measuring any detect able increases in spinal IL-6 mRNA expression following established mo noneuropathy procedures associated with neuropathic pain: spinal nerve cryoneurolysis (SPCN) or spinal nerve tight ligation (SPTL). Using in situ hybridization and a digoxigenin-labeled oligonucleotide, IL-6 mR NA in neurons was significantly elevated at 3 and 7 days post SPCN and 7 days post SPTL in both dorsal and ventral horns. The cellular local ization of the IL-6 mRNA expression was predominately neuronal as conf irmed by NeuN serial staining. For example, in the SPCN 7 day group, I L-6 mRNA cell profiles in the ipsilateral dorsal horn were significant ly different from the normal group (38.7 +/- 12.8 vs. 4.89 +/- 1.6, p < 0.001). These data demonstrate the central, spinal production of a p roinflammatory cytokine in response to a peripheral nerve injury. In a ddition, these results add to the growing body of literature implicati ng these immune products, cytokines, as potential neuromodulators/neur otransmitters and provides further evidence for their role in the noci ceptive processing which leads to chronic pain. (C) 1998 Elsevier Scie nce B.V. All rights reserved.