Interleukin-1α regulates substance P expression and release in adult sensory neurons

Abstract

Nerve injury frequently results in development of chronic, dysesthetic pain and allodynia (painful sensation in response to benign stimulation). Following nerve injury, spinal cord glia become activated and secrete a number of inflammatory cytokines, including interleukin-1 (IL-1), which exists as two genetically distinct proteins, IL-1α and IL-1β. To investigate whether neuropeptide expression could be altered by exposure to these cytokines, dorsal root neurons from mature rats were grown in culture and substance P (SP) expression was analyzed. IL-1α and IL-1β both increased neuronal content of SP. Interestingly, IL-1α was significantly more efficient than IL-1β in inducing SP expression. Cultured neurons exposed to either cytokine secreted substantially more SP with capsaicin stimulation than did control cultures, supporting a physiologic role for these inflammatory cytokines after nerve injury. However, when IL-1β was added in combination with IL-1α to cultured neurons, the amount of SP expressed was significantly lower than that induced by IL-1α alone. Evidence is presented that both cytokines alter SP expression via the IL-1 receptor, and that the signaling pathway involves nerve growth factor (NGF) expression and transcription. In summary, IL-1α was significantly more efficient than IL-1β at up-regulating SP expression than IL-1β. Taken together, these observations suggest an important role for IL-1α in the events following nerve injury.