Activation of kappa opioid receptors in the rostral ventromedial medulla blocks stress-induced antinociception.

Prior work has shown that kappa opioids may attenuate the effects of analgesic mu receptor agonists in some neural circuits related to pain modulation. This study examined whether hypoalgesia following exposure to a signal for shock is attenuated by infusions of the kappa agonist U69593 into the rostral ventromedial medulla (RVM). Rats were trained with paired or unpaired presentations of white noise and foot shock. On test days, tail flick latencies were measured before, during, and after exposure to the auditory conditioned stimulus (CS). One of three doses of U69593 (0.0445, 0.178 and 1.00 microg) or an equivalent volume of saline was injected into the RVM. Rats that had received noise-shock pairings displayed conditional hypoalgesia (CHA) compared to those given unpaired presentations. Expression of CHA was completely blocked by the highest dose of U69593 (1.00 microg) injected 20 min before testing, indicating an antagonistic effect of U69593 on expression of CHA. These findings are discussed in terms of the evidence for antagonism of morphine- and DAMGO-induced hypoalgesia by kappa agonists.