Chronic Pain Produces Reversible Memory Deficits That Depend on Task Difficulty in Rats

J Pain. 2021 Nov;22(11):1467-1476. doi: 10.1016/j.jpain.2021.04.016. Epub 2021 May 20.

Abstract

Cognitive impairment associated with chronic pain remains relatively poorly understood. Use of analgesic drugs and often present co-morbidities in patients can preclude conclusions of causative relationships between chronic pain and cognitive deficits. Here, the impact of pain resulting from spinal nerve ligation (SNL) injury in rats on short and long-term memory was assessed in the novel object recognition task. To understand if chronic pain seizes the limited cognitive resources that are available at any given time, task difficulty was varied by using either very different (ie, easy task) or similar (ie, difficult task) pairs of objects. Nerve-injured, male rats exhibited no short or long-term memory deficits under easy task conditions. However, unlike sham-operated controls, injured rats showed deficits in both short and long-term memory by failing to differentiate similar objects in the difficult task version. In SNL rats, duloxetine produced anti-allodynic effects and ameliorated long-term memory deficits in the difficult task suggesting benefits of pain relief possibly complemented by noradrenergic mediated cognitive enhancement. Together these data suggest chronic pain reversibly takes up a significant amount of limited cognitive resources, leaving sufficient available for easy, but not difficult, tasks. PERSPECTIVE: Memory deficits in a rat model of chronic pain were only seen when the cognitive load was high, ie, in a difficult task. Acute treatment with duloxetine was sufficient to relieve memory deficits, suggesting chronic pain induces memory deficits by seizing limited cognitive resources to the detriment of task-related stimuli.

Keywords: Chronic pain; analgesia; cognition; limited cognitive resources; memory.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chronic Pain* / complications
  • Chronic Pain* / drug therapy
  • Chronic Pain* / physiopathology
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / physiopathology
  • Disease Models, Animal
  • Duloxetine Hydrochloride / administration & dosage
  • Duloxetine Hydrochloride / pharmacology*
  • Male
  • Neuralgia* / complications
  • Neuralgia* / drug therapy
  • Neuralgia* / physiopathology
  • Psychomotor Performance* / drug effects
  • Psychomotor Performance* / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recognition, Psychology* / drug effects
  • Recognition, Psychology* / physiology
  • Serotonin and Noradrenaline Reuptake Inhibitors / administration & dosage
  • Serotonin and Noradrenaline Reuptake Inhibitors / pharmacology*

Substances

  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Duloxetine Hydrochloride