The involvement of norepinephrine in pain modulation in the nucleus accumbens of morphine-dependent rats

Opioids are effective analgesics used clinically for both acute and chronic pain management. However, repeated opioid treatment can induce serious side effects such as nausea, vomiting, drowsiness, respiratory depression, euphoria, dependence, hyperalgesia, and tolerance. The mechanism of noxious information transmission in the central nervous system following dependence is still not clear. Norepinephrine (NE), an important neurotransmitter, participates both in the process of opioid dependence and also pain modulation in the central nervous system. In this study, we examined the role of NE on the evoked discharges of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the nucleus accumbens (NAc) of rats, following the development of morphine dependence. Our results revealed that NE inhibited the evoked discharges of PENs and attenuated the inhibition of PINs, while phentolamine enhanced the evoked discharges of PENs and facilitated the inhibition of PINs. These results indicate that the inhibitory action of NE on pain modulation acts via alpha adrenoceptors in the NAc of morphine-dependent rats.