The role of opioid receptors in the anti-allodynic effect of local montelukast in a rat chronic constriction injury of sciatic nerve model

Abstract

Neuropathic pain is a debilitating and chronic condition that results from damage to the peripheral and central nervous system. The inflammatory mediators such as leukotrienes, and opioidergic pathways are involved in the neuropathic pain generation. The present study aimed to determine the effect of local montelukast and the role of opioid receptors using chronic constriction injury (CCI) of the sciatic nerve in rats. Our results showed that montelukast (1–10 mcg/paw) or morphine (1 and 10 mcg/paw) attenuated the mechanical and cold allodynia at day 7 and 14 post-CCI. The effect of montelukast was attenuated by local pre-treatment with naloxone (20 mcg/paw), and was augmented by an ineffective dose of morphine. Also, the histopathological investigation showed the peripheral anti-inflammatory effect of montelukast in the sciatic-injured paw. Moreover, spinal cord mu-opioid receptor mRNA decreased, and kappa-opioid receptor mRNA increased in rats 14 days after CCI by RT-PCR analyses. However, the administration of montelukast on days 7 and 14 after CCI reversed the observed changes in opioid receptors. Our findings suggested that local montelukast can attenuate neuropathic pain, at least in part, through the peripheral opioid receptors, peripheral anti-inflammatory, and also spinal mu- and kappa-opioid receptors. So, local montelukast could be a novel therapeutic strategy for alleviating neuropathic pain.