Neuropathic Pain Creates an Enduring Prefrontal Cortex Dysfunction Corrected by the Type II Diabetic Drug Metformin But Not by Gabapentin

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Stephanie ShiersTheodore Price

Abstract

Chronic pain patients suffer from pain-related cognitive deficits, even when taking commonly prescribed analgesics. These deficits are likely related to pain-related maladaptive plasticity in the frontal cortex. We sought to model cognitive deficits in mice with neuropathic pain to examine maladaptive morphological plasticity in the mPFC and to assess the effects of several therapeutics. We used an attentional set-shifting task in mice with spared nerve injury (SNI) who received either a single intrathecal injection of an analgesic dose of clonidine, 7 d of 100 mg/kg gabapentin, or 7 d of 200 mg/kg metformin. Male SNI mice were significantly more impaired in the set-shifting task than females. This deficit correlated with a loss of parvalbumin (PV) and reductions in axon initial segment (AIS) length in layers 5/6 of the infralimbic (IL) cortex. Acute pain relief with clonidine had no effect on set-shifting performance, whereas pain relief via 7 day treatment with gabapentin worsened the impairment in both SNI and sham mice. Gabapentin reversed the PV loss in the IL but had no effect on AIS length. Treatment with the AMPK-activator metformin completely reversed the pain-related cognitive impairment and restored AIS length in the...Continue Reading

Citations

Oct 8, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stephanie ShiersTheodore J Price
Aug 15, 2020·Science·Letizia MarvaldiMike Fainzilber
Jan 7, 2020·Behavioral and Brain Functions : BBF·Soonmi WonSung Joong Lee
May 18, 2020·International Journal of Molecular Sciences·Kai K KummerMichaela Kress
Nov 19, 2020·Pediatric Diabetes·Gulcin AkinciEva L Feldman
Nov 13, 2020·Frontiers in Pharmacology·Guadalupe Del Carmen Baeza-FloresVinicio Granados-Soto
Nov 19, 2020·Pharmacological Reviews·Muhammad Saad YousufTheodore J Price
Jan 30, 2021·Trends in Cognitive Sciences·Caroline E PhelpsFrank Porreca
Jan 5, 2021·Diabetes & Metabolism Journal·Jong Chul Won
Dec 15, 2020·Journal of Neuroscience Research·Blake A KimmeyGregory Corder
May 24, 2021·The Journal of Pain : Official Journal of the American Pain Society·Caroline E PhelpsFrank Porreca
Jun 16, 2021·Nature Reviews. Neuroscience·Linette Liqi Tan, Rohini Kuner
Jun 22, 2021·Applied Microbiology and Biotechnology·Qian ZhangZhangyong Song

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