Hypothalamus Pituitary Adrenal axis and stimulatory G proteins signaling role in nociceptive changes induced by forced swim stress

Introduction: Different mechanisms are involved in stress induced analgesia (SIA) and hyperalgesia (SIH). Repeated stress induces development of tolerance to SIA. The role of HPA axis and Gs signaling pathway in these effects are investigated in the current study. Methods: Forced swim stress (5 min/day) in water (20±1 ºC) was employed to adult male Wistar rats (200-250 g). The nociceptive threshold was assessed using tail flick test. Adrenalectomized (ADX) rats were also subjected to stress tests. Oseltamivir was used to block Gs signaling pathway. Results: Stress produced analgesia for 1 h (p<0.001) and hyperalgesia during 3-24 h after its induction (p<0.05). Repeated administration of the stress caused tolerance development to SIA and increased SIH recorded at 24 h after each session (p<0.001). Oseltamivir couldn’t reverse the SIH. Dexamethasone produced hyperalgesia from 30 min (p<0.001) to 24 h after its administration (p<0.01). Repeated injection of dexamethasone increased the hyperalgesia recorded at 24 h after treatment (p<0.001). In ADX animals SIA continued for 24 h (p<0.01). Adrenalectomy attenuated the chronic stress-induced SIA tolerance and eliminated SIH. Conclusion: SIH is suggested to be related to adrenal activity which also has a role in SIA tolerance. Upper parts of HPA axis seems to be responsible for SIA. Oseltamivir could not reverse the SIH. Therefore, the Gs signaling pathway activation by opioid system may not be responsible for SIH.