title: Stress Increases the Negative Effects of Chronic Pain on Hippocampal Neurogenesis.
abstract: BACKGROUND
  Patients with chronic pain often suffer from affective disorders and cognitive decline, which significantly impairs their quality of life. In addition, many of these patients also experience stress unrelated to their illness, which can aggravate their symptoms. These nociceptive inputs are received by the hippocampus, in which maladaptive neuroplastic changes may occur in the conditions of chronic pain. The hippocampus is a structure involved in emotionality, learning, and memory, and the proliferating cells in the granular layer of the hippocampal dentate gyrus respond to chronic pain by slowing their turnover. However, whether the maturation, survival, and integration of newborn cells in the hippocampus are affected by chronic pain remains unclear. In addition, it is unknown whether an added stress may increase this effect.
  
  
  METHODS
  We have evaluated the proliferation, differentiation, and survival of newborn hippocampal cells in a rat model of neuropathic pain (chronic constriction injury), with or without stress (chronic immobilization), by assessing the incorporation of bromodeoxyuridine into proliferating cells and immunostaining.
  
  
  RESULTS
  The data obtained indicated that there was a decrease in the number of proliferating cells 8 days after nerve injury in animals subjected to neuropathic pain, an effect that was exacerbated by stress. Moreover, 4 weeks after nerve injury, neuropathic pain was associated with a loss of neuroblasts and the reduced survival of new mature neurons in the hippocampal granular layer, phenomena that also were increased by stress. By contrast, the rate of differentiation was not affected in this paradigm.
  
  
  CONCLUSIONS
  Neuropathic pain negatively influences hippocampal neurogenesis (proliferation and survival), and this effect is exacerbated by stress. These neuroplastic changes may account for the affective and cognitive impairment seen in patients with chronic pain.
authors.affiliation: From the Department of Neuroscience, University of Cádiz, Cádiz, Spain; CIBER of Mental Health (CIBERSAM), ISCIII, Madrid, Spain; Nursing Faculty "Salus Infirmorum," University of Cádiz, Cádiz, Spain; Department of Psychology, University of Cádiz, Cádiz, Spain; Faculty Medicine, Department of Neuroscience (Pharmacology and Psychiatry), University of Cádiz, Cádiz, Spain; Faculty Medicine, Department of Pharmacology, University Complutense; and IIS Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero-Grimaldi
authors.forename: Esther
authors.initials: E
authors.lastname: Berrocoso
authors.forename: Cristina
authors.initials: C
authors.lastname: Alba-Delgado
authors.forename: Jose Luis M
authors.initials: JLM
authors.lastname: Madrigal
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Perez-Nievas
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Leza
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Mico
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D059350:Chronic Pain / Q000473:pathology* / Q000523:psychology; D006624:Hippocampus / Q000166:cytology* / Q000473:pathology*; D008297:Male; D055495:Neurogenesis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000473:pathology* / Q000523:psychology