N-Ethylmaleimide-Induced Nociceptive Behavior Mediated Through Inhibition of Dynorphin Degradation

N-Ethylmaleimide-Induced Nociceptive Behavior Mediated Through Inhibition of Dynorphin Degradation 

Another set of evidence supports the notion on the pronociceptive functions of dynorphin A in the spinal cord. Behavioral hyperalgesia as a result of inflammation or tissue injury is accompanied by elevations in spinal dynorphin content 

A consensus of different studies appears to be that the spinal dynorphin system plays an inhibitory role in nociceptive transmission mediated through the K-opioid receptor in an acute pain state, and a facilitative role mediated through an NMDA receptor mechanism in a chronic pain state when the K-opioid receptor became tolerant due to sustained activation by endogenous dynorphins (Xu et al., 2004). Our studies suggest that the prodynorphin system also has a pronociceptive function in normal uninjured animals. 

In summary, NEM-induced nociceptive behavior may be mediated through inhibition of the degradation of endogenous dynorphins, presumably big dynorphin that in turn activates the NMDA receptor ion-channel complex by acting on the polyamine recognition site (Fig. 2). 

We would like to express deep gratitude to our collaborators for their kind help, support, and valuable suggestion in this study Dr. Akihisa Esashi, Dr. Aki Taira-Ishii, Mr. Kiyoshi Ohshima, and Mr. Masakazu Shimoda, Tohoku Pharmaceutical University. This study was supported in part by a Grant-in-Aid for Scientific Research (C) (Nos. 07672374, 14572062, and 18613016) from the Japan 

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