Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constrictionin mice

Partial nerve injury is a potential cause of distressing chronic pain for w hich conventional analgesic treatment with opiates or antiinflammatory agen ts is not very effective. Constriction nerve injury, widely used to study n europathic pain, was shown here to induce interleukin-6 (IL-6) mRNA in a su bset of rat primary sensory neurons. When we inflicted chronic nerve constr iction on mice with null mutation of the IL-6 gene, the hypersensitivity to cutaneous heat and pressure that is induced in wild-type mice was not evid ent, the loss of substance P in sensory neurons was excessive and the induc tion of galanin in central sensory projections was reduced. In additional e xperiments, intrathecal infusion of IL-6 in rats was shown to stimulate syn thesis of galanin in approximately one-third of lumbar dorsal root ganglion neurons. The results of these experiments indicate that endogenous IL-6 me diates some of the hypersensitive responses that characterize peripheral ne uropathic pain, and influences two neuropeptides that have been implicated in pain transmission.