title: Enhancement of nerve-injury-induced thermal and mechanical hypersensitivity in adult male and female mice following early life stress.
abstract: OBJECTIVE
  Early life stress contributes to the pathogenesis of psychiatric disorders and chronic pain in adult patients. However, information about the effect of early life stress on chronic pain in mice is limited. In the present study, we evaluated the effect of early life stress on baseline pain sensitivity and thermal or mechanical hypersensitivity induced by nerve injury in male and female mice.
  
  
  METHODS
  Early life stress was induced by maternal separation and social isolation (MSSI). Mice were separated from dam and littermates for 6h/day during postnatal days 15-21 and then were housed individually until the end of the study. At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Thermal and mechanical sensitivity were measured by plantar and von Frey tests.
  
  
  RESULTS
  At 7 weeks of age, MSSI induced depression-like behaviors in both male and female mice, but induced anxiety-like behaviors only in female mice. MSSI had no effect on thermal and mechanical sensitivity before nerve injury. However, MSSI enhanced nerve-injury-induced thermal and mechanical hypersensitivity in both male and female mice.
  
  
  CONCLUSIONS
  MSSI exacerbated neuropathic pain in adult male and female mice. Overall, this model may be useful for understanding the molecular mechanisms underlying the reciprocal relationship between early life stress and chronic pain.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishinaka
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamoto
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. Electronic address: stoku@pharm.kobegakuin.ac.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology; D001010:Anxiety, Separation / Q000473:pathology; D001835:Body Weight / Q000502:physiology; D005260:Female; D005518:Food Preferences; D006358:Hot Temperature; D006930:Hyperalgesia / Q000473:pathology* / Q000523:psychology*; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000473:pathology* / Q000523:psychology*; D010147:Pain Measurement; D010812:Physical Stimulation; D011247:Pregnancy; D012934:Social Isolation / Q000523:psychology; D013315:Stress, Psychological / Q000473:pathology* / Q000523:psychology*
keywords: Anxiety; Depression; Early life stress; Gender difference; Maternal separation; Neuropathic pain