Brief Isolation Changes Nociceptive Behaviors and Compromises Drug Tests in Mice

Rafael Taeho Han, Hyunkyoung Lee, Jae Hee Lee, Sat Byol Lee, Hee Jin Kim, Seung Keun Back, Heung Sik Na

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)749-757
Number of pages9
JournalPain Practice
Issue number6
Publication statusPublished - 2016 Jul 1

Bibliographical note

Publisher Copyright:
© 2015 World Institute of Pain


  • analgesics
  • animal models
  • drug testing
  • isolation
  • pain assessment
  • pain behaviors
  • rodent

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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