montelukast and Neuralgia

Cysteinyl leukotrienes and their receptors have been shown to be involved in the generation of neuropathic pain. We performed this study to determine the antagonistic effect of montelukast, a cysteinyl leukotrienes receptor antagonist, on neuropathic pain and its underlying mechanism.. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After CCI, rats were repeatedly administered montelukast (0.5, 1.0, and 2.0 mg/kg intraperitoneal, once daily) for a period of 14 days. Mechanical withdrawal threshold and thermal withdrawal latency were assessed before surgery and on days 1, 3, 5, 7, and 14 after CCI. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the spinal cord were determined by enzyme-linked immunosorbent assay. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) and activation of nuclear factor-kappaB (NF-κB) were assessed by Western blot. The expression of astrocyte marker glial fibrillary acidic protein and microglia marker Iba-1 and the coexpression of p-p38MAPK and Iba-1 or NF-κB and Iba-1 were observed by immunofluorescent staining.. The CCI group displayed significantly decreased mechanical withdrawal threshold and thermal withdrawal latency on days 1, 3, 5, 7 and 14 compared with sham groups (P <0.05, P < 0.0001), which were markedly increased by montelukast (P < 0.05, P < 0.01, P <0.0001). After administration with montelukast for 14 days, as biological markers of inflammation, the levels of IL-1β (P < 0.0001), IL-6 (P = 0.001 for low dosage, P < 0.0001 for middle and high dosages), and TNF-α (P =0.002, 0.001, < 0.0001 for low, middle, and high dosage, respectively) in the spinal cord were lower than those in the CCI group. Western blot analysis demonstrated that montelukast reduced the elevated expression of p-p38 MAPK (P =0.006, 0.015, < 0.0001 for low, middle, and high dosage, respectively) and NF-κB (P < 0.0001) in the spinal cord induced by CCI. Immunofluorescent staining showed that montelukast could inhibit CCI-induced activation of microglia but not astrocytes in the spinal cord. In addition, montelukast (2.0 mg/kg) significantly decreased the number of p38MAPK and Iba-1 or NF-κBp65 and Iba-1 double-positive cells.. These results suggest that montelukast could effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38MAPK and NF-κB signaling pathways in spinal microglia.

Topics: Acetates; Animals; Astrocytes; Blotting, Western; Chronic Disease; Constriction, Pathologic; Cyclopropanes; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Hot Temperature; Interleukins; Leukotriene Antagonists; Male; Microglia; Neuralgia; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Physical Stimulation; Protein Kinase Inhibitors; Quinolines; Rats; Rats, Sprague-Dawley; Spinal Cord; Sulfides; Tumor Necrosis Factor-alpha

Ischemia-reperfusion (I/R) event in vascular and nervous system has been documented to rising ischemic and vasculitic neuropathic pain, clinically resembles the complex regional pain syndrome (CRPS). The present study evaluated the effect of montelukast, a cysteinyl leukotriene receptor (Cys-LTC(4) and Cys-LTD(4)) antagonist on ischemia -reperfusion (I/R) induced vasculitic neuropathic pain in rats.. Behavioral parameters were assessed at different time intervals (i.e. 0, 1, 7, 14 and 21st day) and biochemical analysis in sciatic nerve tissue samples were also performed along with histopathological studies.. Behavioral pain assessment has shown increase in paw and tail withdrawal threshold in montelukast treated groups against thermal and mechanical stimuli as compared to I/R control group. We observed a decrease in the total calcium, thiobarbituric acid reactive substance (TBARS) and myeloperoxidase (MPO) activity levels, whereas there is rise in reduced glutathione level in montelukast treated groups as compared to I/R control group. However, significant behavioral and biochemical results were observed only in medium and high dose of treated groups which were comparable to normal control group. Moreover, histopathological study has revealed the reduction of I/R induced neuronal edema and axonal degeneration due to montelukast.. Montelukast has ameliorated I/R induced vasculitic neuropathic pain, these effects may be due to inhibition of lipid peroxidation, reduction of oxidative stress, release of inflammatory mediators and neuroprotective actions. Hence, it could be used as a novel therapeutic agent for the management of vasculitic inflammation related neuropathic pain.

Topics: Acetates; Animals; Behavior, Animal; Calcium; Cyclopropanes; Glutathione; Hot Temperature; Immersion; Leukotriene Antagonists; Neuralgia; Pain Measurement; Peroxidase; Physical Stimulation; Quinolines; Rats; Rats, Wistar; Reaction Time; Reperfusion Injury; Sciatic Nerve; Sulfides; Thiobarbituric Acid Reactive Substances; Vasculitis