Involvement of Endogenous Opioid System in Swim Stress-Induced Pain Modulation During the Interphase of the Formalin Test

Introduction: Some evidence demonstrates endogenous inhibitory pathways of pain involved in the interphase (phase between early and later phase) of the formalin test. We previously showed that swimming stress modulates the pain-related behaviors during the interphase of the formalin test. In this study, we evaluated the role of the endogenous opioid system in modulating nociceptive responses of the formalin test. Methods: Swim stress was performed in different heights of water (5, 25, 50 cm) in a swimming tank. The mean nociceptive scores were measured during phase 1 (1-7 min), interphase (8-14 min), and phase 2 (15-90 min) of the formalin test. Opioid receptor antagonist, naloxone (3 mg/kg; IP) was injected immediately before swim stress. Results: Swim stress attenuated nociceptive behaviors in the first phase and increased the duration of interphase in the formalin test in a water-height-dependent manner, compared to the control group. Naloxone significantly increased nociceptive behaviors in the first phase, interphase, and the second phase of the formalin test, compared to the control group. Conclusion: Stress could affect the nociceptive response. Swim stress in different heights of water could have different effects on the nociception in different phases of the formalin test. In addition, the involvement of the endogenous opioid system is further demonstrated in the swim stress-induced modulation of pain behaviors in phase 1, phase 2, as well as interphase of formalin test in rats.