Persistent pain induces mood problems and memory loss by the involvement of cytokines, growth factors, and supraspinal glial cells

Morgana D da Silva; Giselle Guginski; Karina L Sato; Luciana Sayuri Sanada; Kathleen A Sluka; Adair R.S Santos

doi:10.1016/j.bbih.2020.100118

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Persistent pain induces mood problems and memory loss by the involvement of cytokines, growth factors, and supraspinal glial cells

Journal article

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Persistent pain induces mood problems and memory loss by the involvement of cytokines, growth factors, and supraspinal glial cells

Morgana D da Silva, Giselle Guginski, Karina L Sato, Luciana Sayuri Sanada, Kathleen A Sluka and Adair R.S Santos

Brain, behavior, & immunity. Health, Vol.7, p.100118

08/2020

DOI: 10.1016/j.bbih.2020.100118

PMCID: PMC8474185

PMID: 34589875

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Abstract

Lesions of peripheral nerves lead to pain, hyperalgesia, and psychological comorbidities. However, the relationship between mood disorders and neuropathic pain is unclear, as well as the underlying mechanisms related to these disorders. Therefore, we investigated if nerve injury induces depression, anxiety, and cognitive impairment and if there were changes in cytokines, growth factors, and glial cell activation in cortical sites involved in processing pain and mood in animals with nerve injury. Nerve injury was induced by partial sciatic nerve ligation (PSNL) in male Swiss mice and compared to sham-operated animals. Nociceptive behavioral tests to mechanical and thermal (heat and cold) stimuli confirmed the development of hyperalgesia. We further examined mood disorders and memory behaviors. We show nerve injury induces a decrease in mechanical withdrawal thresholds and thermal latency to heat and cold. We also show that nerve injury causes depressive-like and anxiety-like behaviors as well as impairment in short-term memory in mice. There were increases in proinflammatory cytokines as well as Brain-Derived Neurotrophic Factor (BDNF) in the injured nerve. In the spinal cord, there were increases in both pro and anti-inflammatory cytokines, as well as of BDNF and Nerve Growth Factor (NGF). Further, in our data was a decrease in the density of microglia and astrocytes in the hippocampus and increased microglial density in the prefrontal cortex, areas associated with neuropathic pain conditions. [Display omitted] •Partial sciatic nerve ligation induces hypersensitivity in mice.•Nerve injury induces depressant-like and anxiolytic-like behavior and memory loss.•The nerve and spinal cord showed an increase in cytokines and neurotrophins.•Nerve injury decreases density of microglia and astrocytes in the hippocampus.•Also, injury increases microglial density in the prefrontal cortex. Supraspinal astrocytes and microglia are involved in the pathogenesis of PSNL-induced painful neuropathy and mood disorders, as well as the increase of inflammatory factors in the spinal cord and nerve. This measure could potentially help clinicians to develop better treatment for chronic pain problems.

Mood disorders

Glial activation

Inflammatory cytokines

Neurotrophic factors

Neuropathic pain

Details

Title: Subtitle: Persistent pain induces mood problems and memory loss by the involvement of cytokines, growth factors, and supraspinal glial cells
Creators: Morgana D da Silva - Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center for Biological Sciences, Federal University of Santa Catarina, University Campus, Trindade, Florianópolis, SC, 88040-900, Brazil
Giselle Guginski - Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, University Campus, Trindade, Florianópolis, SC, 88040-900, Brazil
Karina L Sato - Department of Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, #1-252 MEB, Iowa City, IA, 52241, USA
Luciana Sayuri Sanada - Department of Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, #1-252 MEB, Iowa City, IA, 52241, USA
Kathleen A Sluka - Department of Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, #1-252 MEB, Iowa City, IA, 52241, USA
Adair R.S Santos - Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center for Biological Sciences, Federal University of Santa Catarina, University Campus, Trindade, Florianópolis, SC, 88040-900, Brazil
Resource Type: Journal article
Publication Details: Brain, behavior, & immunity. Health, Vol.7, p.100118
DOI: 10.1016/j.bbih.2020.100118
PMID: 34589875
PMCID: PMC8474185
NLM abbreviation: Brain Behav Immun
ISSN: 0889-1591
eISSN: 1090-2139
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/501100003593, name: Conselho Nacional de Desenvolvimento Científico e Tecnológico; DOI: 10.13039/501100005667, name: Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina; DOI: 10.13039/501100002322, name: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; name: Programa INCT-INOVAMED, award: 465430/2014-7; DOI: 10.13039/501100002322, name: CAPES, award: AR061371; DOI: 10.13039/501100003593, name: CNPq
Language: English
Date published: 08/2020
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984072093702771

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