Brief Isolation Changes Nociceptive Behaviors and Compromises Drug Tests in Mice

Abstract

Herding with a litter is known to comfort rodents, whereas isolation and grouping with noncagemates provoke stress. The effects of stress induced by isolation and grouping with noncagemates on pain responses, and their underlying mechanisms remain elusive. We assessed the effect of isolation, a common condition during behavioral tests, and of grouping on defecation and pain behaviors of mice. Fecal pellets were counted 2 hours after exposure to the test chamber. It is significantly more in the isolated mice than in the grouped mice. Hindpaw withdrawal threshold and withdrawal latency were adopted as the indicatives of mechanical and thermal pain sensitivities, respectively. Interestingly, isolated mice showed higher pain thresholds than mice grouping with cagemates, and even those with noncagemates, indicating analgesic effects. Such effects were reduced by intrathecal injection of 0.01 mg/kg of naloxone (opioid receptor antagonist), atosiban (oxytocin and vasopressin receptor antagonist), and ketanserin (5-HT receptor antagonist). Intraperitoneal delivery of 1 mg/kg of naloxone and atosiban, but not ketanserin, also alleviated the isolation-induced analgesic effects. In contrast, these drugs at the same dose had no significant effect on the mice grouping with cagemates. In addition, the effect of morphine on thermal pain was more robust in the mice grouping with cagemates than in the isolated mice. These data demonstrated that brief isolation caused analgesia, mediated by endogenous opioidergic, oxytocinergic, and serotonergic pathways. These results indicate that isolation during pain behavioral tests can affect pain responses and the efficacy of drugs; thus, nociception tests should be conducted in grouping.

Long-Term Isolation Elicits Depression and Anxiety-Related Behaviors by Reducing Oxytocin-Induced GABAergic Transmission in Central Amygdala

“…Social isolation was reported to be associated with down-regulation of hypothalamic OXTR mRNA transcription ( Pournajafi-Nazarloo et al, 2013 ). Moreover, deprivation of social interactions and chronic stress produced by isolation are involved with not only decrease but also increase in the secretion of OXT ( Pournajafi-Nazarloo et al, 2013 ; Han et al, 2016b ). Thus, our observation that the mRNA transcription of OXTR, but not that of V1aRA, was reduced in the CeA after the 5-week isolation ( Figures 4A,B ) may be attributed to two possible scenarios.…”

“…OXT has attracted attention for its role in mediating social stress and modulating the activity of the amygdala ( Huber et al, 2005 ; Viviani et al, 2011 ; Olff et al, 2013 ). OXT was reported to mediate isolation-induced behavioral changes and elevate social interactions in experimental animals and human studies ( Han et al, 2016b ; Yatawara et al, 2016 ). In addition, recent studies have implicated the potential roles of OXT in anxiolysis and shown therapeutic benefits of OXT for subsets of patients with depressive disorders ( Slattery and Neumann, 2010b ).…”

Effect of Acute Brief Social Isolation on Visceral Pain

“…The number of fecal bolus deposited in the cage was counted for 2 hours. 14 The number of fecal bolus deposited in the cage of group rearing rats was monitored via video recording.…”

Effects of exogenous oxytocin and atosiban antagonist on GABA in different region of brain

“…OT 0.0116 mg/kg and OTA 1 mg/kg was prepared in 0.89% normal saline. The dose of OT and OTA was finalized after reviewing various previous studies and confirmed through experimental investigation (Han et al, 2016; Mizuno et al, 2015; Teng et al, 2016).…”