reparixin and Pain

Interleukin-8 (IL-8) is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC), is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals 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.

Topics: Animals; Freund's Adjuvant; Glutamates; Gyrus Cinguli; Hyperalgesia; In Vitro Techniques; Inflammation; Interleukin-8; Mice; Mice, Inbred C57BL; Pain; Prefrontal Cortex; Receptors, N-Methyl-D-Aspartate; Sulfonamides; Synaptic Transmission

Autologous nucleus pulposus obtained from coccygeal intervertebral discs was grafted on the proximal of L5 dorsal root ganglion. Pain behavior, mRNA expression of Interleukin-8 (IL-8), and immunohistochemical changes were assessed.. The purpose of this study is to investigate temporal changes of IL-8 expression in the spinal cord and dorsal root ganglion and the pain-related behaviors with time course and to elucidate whether repertaxin (IL-8 receptor inhibitor) attenuates pain-related behaviors in a rat model of lumbar disc herniation.. Inflammatory mediators like cytokines and chemokines have been implicated in radicular pain because of disc herniation. IL-8, known as CXCL8, is a chemokine, which has been reported to be associated with painful degenerative disc disorders and chronic inflammatory pain states.. Lumbar disc herniated rat model was made by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the dorsal root ganglion. Rats were tested for mechanical allodynia and thermal hyperalgesia at 2 days before surgery, and on days 1, 5, 10, 20, 30, 40, 50, and 60 postoperatively. Experimental group was intrathecally injected with the IL-8 receptor inhibitor at L5 level on postoperative day 10. Mechanical allodynia of the plantar surface of both hindpaw was tested on 30 minutes, 1, 3 hours, 1, 3, 5, and 10 days after administration. For the staining of astrocytes and microglia, immunohistochemical study was done 20 days after surgery.. Mechanical allodynia in ipsilateral hindpaw developed 1 day after surgery and lasted until 60 days and thermal withdrawal latency decreased significantly on the ipsilateral side 10 days after surgery and gradually increased through day 60. The IL-8 receptor inhibitor attenuated the mechanical allodynia caused by nucleus pulposus when it was administered on postoperative day 10 and reduced microglial activation and phosphorylated form of mitogen-activated protein kinase (pERK) expression in the spinal dorsal horn.. IL-8 might be a potential therapeutic target in chronic radicular neuropathic pain because of disc herniation, CXCL8 inhibitor could be one of its promising therapeutic agents.

Topics: Animals; Chemokine CXCL1; Disease Models, Animal; Ganglia, Spinal; Gene Expression; Hyperalgesia; Immunohistochemistry; Interleukin-8; Intervertebral Disc Displacement; Lumbar Vertebrae; Male; Pain; Pain Measurement; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-8A; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spinal Cord; Sulfonamides; Time Factors