Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC), and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA) in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA) revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice.Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.Chemokines, a family of proinflammatory cytokines play a role in immune system regulation, cell growth, cell development, and inflammation [1]. Interleukin-8 (IL-8), also known as CXCL8, is an α chemokine and its main function is chemotaxis of neutrophils and T lymphocytes [2]. In the immune system, IL-8 exerts its biological action by binding to seven-transmembrane G-protein-coupled receptors named CXCR1 and CXCR2. In the CNS, CXCR2 receptors have been described on astrocytes, microglia, and neurons [3]. The chemokine IL-8 is known to be synthesized by microglial cells and astrocytes [4]. IL-8 may be an important factor in intercellular communication between glia and neurons by rapidly altering the excitability of neurons, probably through presynaptic mechanisms [5]. Repertaxin is a new non-competitive allosteric blocker of IL-8 receptors (CXCR1/R2), which by locking CXCR1/R2 in an inactive conformation prevents receptor signaling and human polymorphonuclear leukocyte (PMN) chemotaxis [6].Studies using diffe