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

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.

Kinin B1 and B2 Receptors Contribute to Cisplatin-Induced Painful Peripheral Neuropathy in Male Mice

“…These discrepancies between the results may be due to the different administration schedules, doses of cisplatin, or differences between the animal strains tested [ 74 , 75 , 76 ]. Thus, it is important to better elucidate such conditions underlying chemotherapeutic treatment, as well as cognitive impairment and mood disorders, in experimental models, since they can influence or be influenced by chronic pain states [ 71 , 77 ].…”

The effect of gabapentin and pregabalin administration on memory in clinical and preclinical studies: a meta-analysis and systematic review

“…Pain and chronic pain are a company by several cognitive disruptions, leading to problems in attention, spatial memory, recognition memory, and decision-making [72,73]. Porta et al reported the presence of neuropathic pain mice was associated with increased anxiety-and depressive-like behaviors, and reduced memory functions, chronic PGB treatment improved the nociceptive, anxiety-like, as well as memory deficit, but did not modify the depressive-like behavior [56].…”

Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain

“…For post-PNI chronic pain-evoked cognitive deficit, memory dysfunction, anxiety, and depression, NIF and neurogenic changes in the hippocampus, the key structure to process memory, learning, and emotion, have been identified as primary operators [ 112 – 115 ]. Yet, no published data has been available concerning associations between lower thoracic SCI, NP, and alterations of hippocampal NIF and neurogenesis.…”