Partial nerve injury is a potential cause of distressing chronic pain for which conventional analgesic treatment with opiates or anti‐inflammatory agents is not very effective. Constriction nerve injury, widely used to study neuropathic pain, was shown here to induce interleukin‐6 (IL‐6) mRNA in a subset of rat primary sensory neurons. When we inflicted chronic nerve constriction 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 evident, the loss of substance P in sensory neurons was excessive and the induction of galanin in central sensory projections was reduced. In additional experiments, intrathecal infusion of IL‐6 in rats was shown to stimulate synthesis of galanin in approximately one‐third of lumbar dorsal root ganglion neurons. The results of these experiments indicate that endogenous IL‐6 mediates some of the hypersensitive responses that characterize peripheral neuropathic pain, and influences two neuropeptides that have been implicated in pain transmission.