Pain Inhibition by Endomorphins

: Spinal analgesic effects of endomorphin‐1 and endomorphin‐2 were studied during acute, inflammatory, and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin‐1 and endomorphin‐2 (2.5‐10 μg i.t.), as well as their analogues, increased the tail‐flick and the paw pressure latencies. In a model of inflammatory pain, the formalin‐induced behavior was attenuated by endomorphins; however, the effect studied was not dose‐dependent and was less pronounced in comparison with that evoked by morphine. On the other hand, in rats with a sciatic nerve injury (crush), endomorphins antagonized allodynia in a dose‐dependent manner, whereas morphine was found to be ineffective in a similar dose range. Endomorphins also exhibited an antinociceptive potency in rats tolerant to morphine. In conclusion, our results show a powerful analgesic action of endomorphins at the spinal level. The most interesting finding is a strong effect of endomorphins in neuropathic pain, which opens up a possibility of using these compounds in pain therapy.