Chronic pain causes a persistent anxiety state leading to increased ethanol intake in CD1 mice

J Psychopharmacol. 2016 Feb;30(2):188-203. doi: 10.1177/0269881115622238. Epub 2015 Dec 17.

Abstract

Mood disorders and chronic pain are closely linked, but limited progress has been made in understanding the role of chronic and neuropathic pain in the aetiopathogenesis of depression. To explore the pathological mechanisms that mediate the association between pain and depressive-like behaviours, we studied the time-dependent effect of neuropathic pain on the development of anxiety-like and despair behaviours in CD1 mice. We analysed behavioural data, neuroinflammation reactions and changes in neurotransmitter (glutamate and serotonin) levels in the mouse prefrontal cortex. Sciatic-operated mice displayed long-lasting anxiety-like and despair behaviours, starting 5 and 20 days after partial sciatic nerve ligation, respectively. Glutamatergic neurotransmission and IL-1β cytokine expression were enhanced in the prefrontal cortex of mice with neuropathic pain. We found no change in serotonin metabolism, cytokine IL-6 or brain-derived neurotrophic factor levels. While sciatic-operated mice exposed to intermittent ethanol intake (20% v/v) using the drinking in the dark procedure consumed higher amounts of ethanol than sham-operated mice, thermal allodynia and despair behaviour were not attenuated by ethanol consumption. Our findings reveal an association between glutamatergic neurotransmission and pain-induced mood disorders, and indicate that moderate ethanol consumption does not relieve nociceptive and depressive behaviours associated with chronic pain in mice.

Keywords: DID test; Neuropathic pain; ethanol intake; glutamate; mood disorders; thermal allodynia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / epidemiology*
  • Animals
  • Anxiety / etiology*
  • Anxiety / psychology
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / metabolism
  • Chronic Pain / complications*
  • Chronic Pain / psychology
  • Depression / etiology
  • Depression / psychology
  • Disease Models, Animal
  • Ethanol / administration & dosage*
  • Glutamic Acid / metabolism
  • Hyperalgesia / complications
  • Hyperalgesia / psychology
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Prefrontal Cortex / metabolism
  • Serotonin / metabolism
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • Interleukin-6
  • Serotonin
  • Ethanol
  • Glutamic Acid