Background: Lithium has been shown to relieve mania and induce antinociception. In the present study, SWIM STRESS at 8°C induced antinociception in both phases of the formalin test. Intraperitoneal administration of lithium chloride (LiCl) (0.05, 0.25, and 0.5 mg/kg) also induced antinociception in both phases of the formalin test. Methods: Antinociception was assessed by the formalin test method. SWIM STRESS was achieved in the 8°C water in a container 5 cm in diameter and 20 cm tall filled with water do a depth of 11 cm. Results: The drug (0.5 and 5 mg/kg) potentiated SWIM STRESS-induced antinociception in the second phase of the test. Repeated exposure to water SWIMming STRESS with a period of 40 sec, once daily for three days, in combination with lithium chloride did not alter STRESS-induced antinociception in either phases of the formalin test, when SWIM STRESS-induced antinociception was tested on the fourth day. Subchronic treatment with morphine (25 mg/kg), once daily for three days, in the presence or absence of lithium chloride (5 mg/kg) did not alter SWIM STRESS-induced antinociception, either, when SWIM STRESS-induced antinociception was tested on the fourth day. Conclusion: It may be concluded that lithium chloride potentiates SWIM STRESS-induced antinociception, but the drug has no influence on the response of subchronic administration SWIM STRESS or morphine.

Introduction: The formalin test is the most accepted chemical test for evaluation of nociception. It requires the injection of an adequate amount of formalin into the surface of the hindpaw. Formalin test consists of phase 1 (0-7 min) and phase 2 (15-60) in which the animal shows painful behaviors. These phases are separated with a quiet phase named interphase, in which the nociceptive responses are decreased or completely disappeared.Methods: The goal of the current study was to evaluate the effects of SWIM STRESS at different heights of water on different phases of the formalin test in male rats.Results: SWIM STRESS decreased nociceptive behaviors in first phase and prolonged interphase or delayed the start of second phase in a water height dependent manner. SWIM STRESS in 25 and 50cm completely abolished the nociceptive behaviors in phase 1.Discussion: The present results showed different pain modulation during different phases of the formalin test and elucidated the impact of SWIM STRESS on duration of interphase. Interphase considered as an inactive period, but a recent research has shown that active inhibitory mechanisms are involved in the modulation of pain during this period. Therefore, SWIM STRESS may be considered as a useful tool for study of the basic inhibitory mechanisms underlying attenuation of nociceptive behaviors between phase 1 and 2 of the formalin test.

STRESS and chronic pain have been shown to prevent the development of tolerance to morphine analgesia, which appears to be related to neuroendocrine activity and alternation in neurochemicals. Also the involvement of nitric oxide (NO) has been implicated in tolerance to morphine analgesia. In our pervious study, we showed that co-administration of SWIM STRESS (ss) with chronic morphine, prevents the development of morphine tolerance. In this study the probable interactions between SWIM STRESS and nitric oxide level on development of morphine tolerance were investigated. Adult male NMRI rats weighing 180-220 g were divided into control and experimental groups (N=8) that received morphine 20 mg/kg (i.p.) for 4 days, SWIM STRESS 4 minutes for 4 days at 20oC water and combination of both SWIM STRESS and morphine injection for 4 days. Nitric oxide was measured as indicator of NO by Griess methods. SWIM STRESS raised NO level (P<0.001). Combination of morphine injection and SWIM STRESS significantly decreased nitric oxide level compared to chronic morphine treated group (P<0.001). These data suggest that at least two parallel systems may be activated during STRESS: 1. inbibition of morphine tolerance may be mediated by STRESS via activation of HPA axis as described by other reports in case of pain STRESS, and HPA axis activation in tolerance prevention, and 2. suppression of nitric oxide synthase (NOS) activity.

Objective (s): 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.Materials and Methods: 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 (50ml injection of formalin 2% subcutaneously into hind paw) and pain related behaviors were monitored for 90 min.Results: 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).Conclusion: The result of the present study demonstrated that permanent inactivation of RVM can potentiate STRESS-induced analgesia in formalin test.