interleukin-8 and Neuralgia

Cytokines can be divided into two types： proinflammatory cytokines and anti-inflammatory cytokines. Proinflammatory cytokines are a kind of small molecular peptides synthesized and excreted by immune and non-immune cells, which can regulate a variety of physiological functions and play an important role in the process of trauma, pain and infection. Proinflammatory cytokines include TNF, IL-1, IL-6 and IL-8. More and more evidences suggest that proinflammatory cytokines(PICs), such as interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α), are induced in the spinal cord(SC) and dorsal root ganglion (DRG) under various injury conditions, and contribute to pain hypersensitivity. In recent years, with the deepening of studies on neuropathic pain mechanism and the increasing expansion of the neuroinflammation study field, the action mechanisms of cytokines and molecules in regulating cytokines in neuropathic pain are expected to provide new targets for the development of analgesic drugs. This review aims to provide an overview of inflammatory mechanisms for proinflammatory cytokines TNF-α, IL-1β, IL-6, with a focus on neuropathic pain.

Topics: Ganglia, Spinal; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Neuralgia; Spinal Cord; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Herpes Zoster; Humans; Injections, Epidural; Interleukin-8; Methylprednisolone; Methylprednisolone Acetate; Neuralgia; Predictive Value of Tests; Subarachnoid Space

There is no effective treatment for intractable postherpetic neuralgia. Because there is evidence that postherpetic neuralgia has an inflammatory component, we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder.. We enrolled 277 patients who had had intractable postherpetic neuralgia for at least one year, 270 of whom were followed for two years. The patients were randomly assigned to receive intrathecal methylprednisolone and lidocaine (3 ml of 3 percent lidocaine with 60 mg of methylprednisolone acetate, 89 patients), lidocaine alone (3 ml of 3 percent lidocaine, 91 patients), or no treatment (90 patients) once per week for up to four weeks. Each weekly dose was injected into the lumbar intrathecal space. Pain was evaluated before randomization, at the end of the treatment period, and then four weeks, one year, and two years later. Samples of cerebrospinal fluid were obtained for measurement of interleukin-8 before and at the end of the treatment period.. There was minimal change in the degree of pain in the lidocaine-only and control groups during and after the treatment period. In the methylprednisolone-lidocaine group, the intensity and area of pain decreased, and the use of the nonsteroidal antiinflammatory drug diclofenac declined by more than 70 percent four weeks after the end of treatment. No complications related to intrathecal methylprednisolone were observed. Before treatment, the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients (r=-0.49, P<0.001). In the patients who received methylprednisolone, interleukin-8 concentrations decreased by 50 percent, and this decrease correlated with the duration of neuralgia and with the extent of global pain relief (P<0.001 for both comparisons).. The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.

Topics: Aged; Anesthetics, Local; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Therapy, Combination; Female; Herpes Zoster; Humans; Injections, Spinal; Interleukin-8; Lidocaine; Male; Methylprednisolone; Middle Aged; Neuralgia; Pain; Pain Measurement; Single-Blind Method

Repulsive guidance molecule-a (RGMa) is a glycosylphosphatidylinositol-linked glycoprotein which has multiple functions including axon growth inhibition and immune regulation. However, its role in the pathophysiology of neuromyelitis optica (NMO) is poorly understood. Perivascular astrocytopathy, which is induced by the leakage of aquaporin-4 (AQP4)-specific IgG into the central nervous system parenchyma, is a key feature of NMO pathology. We investigated the RGMa involvement in the pathology of NMO astrocytopathy, and tested a therapeutic potential of humanized anti-RGMa monoclonal antibody (RGMa-mAb).. Using a clinically relevant NMO rat model, we evaluated the therapeutic effect of a RGMa-mAb by behavioral testing, immunohistochemistry, and gene expression assay. We further performed in vitro experiments to address the RGMa-signaling in macrophages.. In both NMO rats and an NMO-autopsied sample, RGMa was expressed by the spared neurons and astrocytes, whereas its receptor neogenin was expressed by infiltrating macrophages. AQP4-IgG-induced astrocytopathy and clinical exacerbation in NMO rats were ameliorated by RGMa-mAb treatment. RGMa-mAb treatment significantly suppressed neutrophil infiltration, and decreased the expression of neutrophil chemoattractants. Interestingly, neogenin-expressing macrophages accumulated in the lesion expressed CXCL2, a strong neutrophil chemoattractant, and further analysis revealed that RGMa directly regulated CXCL2 expression in macrophages. Finally, we found that our NMO rats developed neuropathic pain, and RGMa-mAb treatment effectively ameliorated the severity of neuropathic pain.. RGMa signaling in infiltrated macrophages is a critical driver of neutrophil-related astrocytopathy in NMO lesions, and RGMa-mAb may provide an efficient therapeutic strategy for NMO-associated neuropathic pain and motor deficits in patients with NMO. ANN NEUROL 2022;91:532-547.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aquaporin 4; GPI-Linked Proteins; Humans; Immunoglobulin G; Interleukin-8; Macrophages; Membrane Proteins; Nerve Tissue Proteins; Neuralgia; Neuromyelitis Optica; Neutrophils; Rats

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of several anti-neoplastics and a main cause of sensory disturbances in cancer survivors, negatively impacting patients' quality of life. Peripheral nerve degeneration or small fibre neuropathy is generally accepted as the underlying mechanism in the development of CIPN. Recent evidence has contributed to clarify the determinant role of cytokines and chemokines in the process leading to neuronal hyperexcitability. Exposure to oxaliplatin triggers alterations in peripheral neuropathic pathways previously linked to IL-8 pathway. We investigated a novel selective inhibitor of IL-8 receptors, DF2726A, and showed its effects in counteracting CINP pathways, extending the relevance of the activation of IL-8 pathway to the class of platinum chemotherapeutics. Based on our results, we suggest that DF2726A might be a promising candidate for clinical treatment of CIPN conditions due to its efficacy and optimized pharmacokinetic/pharmacodynamic profile.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytokines; Humans; Interleukin-8; Molecular Targeted Therapy; Neuralgia; Oxaliplatin; Signal Transduction

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that represents a frequent and serious consequence of chemotherapy agents. Over the last years, significant progress has been achieved in elucidating the underlying pathogenesis of CIPN. The interference of taxanes with microtubule has been proposed as a mechanism that leads to altered axonal transport and to permanent neurological damages. The inflammatory process activated by chemotherapeutic agents has been considered as a potential trigger of nociceptive process in CIPN.In this study we investigated the effect of reparixin, an inhibitor of CXCR1/CXCR2, in suppressing the development of paclitaxel-induced nociception in rats. Moreover, reparixin activity in reversing the neurotoxic effects induced by paclitaxel or GRO/KC in F11 cells was also analyzed.Reparixin administered by continuous infusion ameliorated paclitaxel-induced mechanical and cold allodynia in rats. In F11 cells, reparixin was able to inhibit the increase of acetyladed α-tubulin induced both by paclitaxel and GRO/KC. The subsequent experiments were performed in order to dissect the signal transduction pathways under GRO/KC control, eventually modulated by paclitaxel and/or reparixin. To this aim we found that reparixin significantly counteracted p-FAK, p-JAK2/p-STAT3, and PI3K-p-cortactin activation induced either by paclitaxel or GRO/KC.Overall the present results have identified IL-8/CXCR1/2 pathway as a mechanism involved in paclitaxel-induced peripheral neuropathy. In particular, the obtained data suggest that the inhibition of CXCR1/2 combined with standard taxane therapy, in addition to potentiating the taxane anti-tumor activity can reduce chemotherapy-induced neurotoxicity, thus giving some insight for the development of novel treatments.

Topics: Animals; Antineoplastic Agents, Phytogenic; Interleukin-8; Male; Neuralgia; Paclitaxel; Rats; Rats, Wistar; Receptors, Interleukin-8A; Receptors, Interleukin-8B

Interleukin-8 (IL-8) is a pro-inflammatory cytokine that has been shown to play a role in inflammatory and autoimmune disorders. The objective of the present study was to assess the levels of IL-8 in rat serum, dorsal root ganglion (DRG) and the sciatic nerve following four different forms of sciatic nerve injury. The models used to induce the injury included partial sciatic ligation (PSL), chronic constriction injury (CCI), perineural inflammation (neuritis) and complete sciatic transection (CST). Mechanical and thermal hyperalgesia were detected by measuring withdrawal responses from a mechanical stimulus and withdrawal latency from thermal stimulation. Enzyme-linked immunosorbent assays (ELISA) was used to assess the IL-8 levels in the affected and contralateral sciatic nerves. Rats exposed to PSL and neuritis developed significant nociceptive response (mechanical and thermal hyperalgesia) in the affected side at three days post-surgery whereas the CCI group at eight days post-surgery. No mechanical or thermal hyperalgesia was observed in rats exposed to CST at either three or eight days postsurgery. Additionally, IL-8 levels were significantly increased in the injured sciatic nerve at 3 and 8days following PSL and neuritis as well as at 8days following CCI when compared to naïve animals. A significant up regulation of IL-8 levels was observed in the ipsilateral DRG at 3 and 8days following CST compared to naïve animals. The serum IL-8 levels remained unchanged in all models of nerve damage. The results of this study suggest that IL-8's role in the neuropathic pain etiology may be specific to nerve injury type.

Topics: Animals; Disease Models, Animal; Ganglia, Spinal; Interleukin-8; Male; Neuralgia; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Sciatic Neuropathy

Other than age, the risk factors for postherpetic neuralgia are not well established. We studied whether the concentration of interleukin 8 in the cerebrospinal fluid is associated with the risk of postherpetic neuralgia.. We enrolled 170 patients more than 50 years old who had a typical painful and nontrigeminal herpetic rash. Patients were treated with acyclovir; no corticosteroids were given. Cerebrospinal fluid was taken for analysis of interleukin 8 during and at full crusting of the herpetic rash. Age, sex, comorbid conditions, prodromal pain, localization and severity of herpetic rash, number of skin lesions, and degree of pain were recorded. We used multivariate logistic regression modeling to identify significant predictive factors. Receiver operating characteristic (ROC) curves were evaluated to determine the contribution of each factor.. Six months after healing, 31 patients (18%) had postherpetic neuralgia; 27 patients still had it after 1 year. Only three variables-age (odds ratio [OR] = 2.7 per 10-year increase; 95% confidence interval [CI]: 1.2 to 6.2), acute pain (OR = 1.8 per unit increase in visual analog scale; 95% CI: 1.2 to 2.8), and interleukin 8 concentration in the cerebrospinal fluid at full crusting of the herpetic rash (OR = 1.6 per 20-microg/L increase; 95% CI: 1.3 to 2.0)-were significant predictors of postherpetic neuralgia at 1 year. Interleukin 8 concentration also had the highest area under the ROC curve at these evaluation points (P <0.001).. Our results suggest that interleukin 8 concentration in the cerebrospinal fluid at full crusting of herpetic rash may be useful for identifying patients who are likely to develop intractable postherpetic neuralgia.

Topics: Aged; Biomarkers; Female; Herpes Zoster; Humans; Interleukin-8; Logistic Models; Male; Neuralgia; Pain Measurement; Risk Factors; ROC Curve

Cerebrospinal fluid biomarkers were evaluated in a setup using established pig models to mimic clinical disc herniation.. To investigate biomarkers for nerve tissue injury, inflammation, and pain in cerebrospinal fluid after mechanical compression and/or nucleus pulposus application to spinal nerve roots.. The association between mechanical compression, biochemical effects of nucleus pulposus, and nerve root injury in degenerative disc disorders is incompletely investigated.. The unilateral S1 nerve root was exposed in 20 pigs. The animals were divided into four groups (n = 5 each): 1) slow-onset mechanical compression with an ameroid constrictor; 2) autologous nucleus pulposus application; 3) mechanical compression plus nucleus pulposus; and 4) sham operation. After 1 week, 6 mL of cerebrospinal fluid was collected, and four structural nerve proteins, neurofilaments, S-100, glial fibrillary acidic protein, neuron-specific enolase, the proinflammatory cytokine interleukin-8, the neurotransmitter nociceptin, and substance P endopeptidase activity were analyzed using immunoassays.. The concentration of neurofilament was increased in the mechanical compression group (17.0 microg/L +/- 5.0) and in the mechanical compression plus nucleus pulposus group (19.8 +/- 12.1 microg/L) compared with the sham group (0.9 +/- 0.9 microg/L) and the nucleus pulposus group (0.4 +/- 0.1 microg/L) (P < 0.01 for both). The concentration of nociceptin was increased significantly in the mechanical compression group (24.0 +/- 8.6 fm/mL) and in the mechanical compression plus nucleus pulposus group (31.2 +/- 6.6 fm/mL) compared with the sham group (7.0 +/- 1.3 fm/mL) (P < 0.05 and P < 0.01, respectively). A correlation was found between concentrations of neurofilament and nociceptin (r = 0.50, P < 0.05). There were no intergroup differences regarding glial fibrillary acidic protein, neuron-specific enolase, S-100, interleukin-8, or substance P endopeptidase activity.. The present study demonstrates increased concentrations of neurofilament and nociceptin in cerebrospinal fluid after nerve root compression. A simultaneous application of nucleus pulposus did not increase the response.

Topics: Animals; Biomarkers; Cerebrospinal Fluid Proteins; Glial Fibrillary Acidic Protein; Interleukin-8; Intervertebral Disc; Lumbar Vertebrae; Metalloendopeptidases; Nerve Tissue Proteins; Neuralgia; Neurofilament Proteins; Nociceptin; Opioid Peptides; Phosphopyruvate Hydratase; Pressure; S100 Proteins; Spinal Nerve Roots; Stress, Mechanical; Swine; Tissue Extracts

Topics: Anti-Inflammatory Agents; Arachnoiditis; Herpes Zoster; Humans; Injections, Spinal; Interleukin-8; Meningitis; Methylprednisolone; Neuralgia