Permanent lesion in rostral ventromedial medulla potentiates swim stress-induced analgesia in formalin test

There are many reports about the role of rostral ventromedial medulla (RVM) in modulating stress-induced analgesia (SIA). In the previous study we demonstrated that temporal inactivation of RVM by lidocaine potentiated stress-induced analgesia. In this study, we investigated the effect of permanent lesion of the RVM on SIA by using formalin test as a model of acute inflammatory pain. Three sets of experiments were conducted: (1) Application of stress protocol (2) Formalin injection after exposing the animals to the swim stress (3) Either the relevant vehicle or dopamine receptor 1 (D1) agonist R-SKF38393 was injected into the RVM to cause a lesion. For permanent lesion of RVM, R-SKF38393 was injected into the RVM. Forced swim stress in water was employed in adult male rats. Nociceptive responses were measured by formalin test (50µl injection of formalin 2% subcutaneously into hind paw) and pain related behaviors were monitored for 90 min. In the unstressed rats, permanent lesion of the RVM by R-SKF38393 decreased formalin-induced nociceptive behaviors in phase 1, while in stressed rats, injection of R-SKF38393 into the RVM potentiated swim stress-induced antinociception in phase 1 and interphase, phase 2A of formalin test. Furthermore, R-SKF38393 had pronociceptive effects in phase2B whereas injections of R-SKF38393 resulted in significant difference in nociceptive bahaviours in all phases of formalin test (P<0.05). The result of the present study demonstrated that permanent inactivation of RVM can potentiate stress-induced analgesia in formalin test.