Opioid receptor activation is involved in neuroprotection induced by TRPV1 channel activation against excitotoxicity in the rat retina.

Recently, we reported that capsaicin, a transient receptor potential vanilloid type1 (TRPV1) agonist, protected against excitotoxicity induced by intravitreal N-methyl-D-aspartic acid (NMDA) in the rats in vivo. It has been reported that morphine, an opioid receptor agonist, ameliorated excitotoxicity induced by ischemia-reperfusion in the retina, and that capsaicin-induced neuroprotection was reduced by naloxone, an opioid receptor antagonist in the brain. The aim of the present study is to clarify whether activation of opioid receptors is involved in the capsaicin-induced neuroprotection in the retina. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal NMDA injection (200nmol/eye). Capsaicin (5.0nmol/eye), calcitonin gene-related peptide (CGRP; 0.05pmol/eye), β-endorphin (0.5 pmol/eye), substance P (5nmol/eye), and naloxone (0.5nmol/eye) were intravitreally administered simultaneously with NMDA. Morphometric evaluation 7 days after NMDA injection showed that intravitreal NMDA injection resulted in ganglion cell loss. Capsaicin, CGRP, β-endorphin, and substance P prevented this damage. Treatment with naloxone (0.5nmol/eye) almost completely negated the protective effects of capsaicin, CGRP, β-endorphin, and substance P in the NMDA-injected rats. These results suggested that activation of opioid receptors is possibly involved in the protective effect of capsaicin.