Suppression of Pain in the Late Phase of Chronic Trigeminal Neuropathic Pain Failed to Rescue the Decision-Making Deficits in Rats

Abstract

Trigeminal neuropathic pain (TNP) led to vital cognitive functional deficits such as impaired decision-making abilities in a rat gambling task. Chronic TNP caused hypomyelination in the anterior cingulate cortex (ACC) associated with decreased synchronization between ACC spikes and basal lateral amygdala (BLA) theta oscillations. The aim of this study was to investigate the effect of pain suppression on cognitive impairment in the early or late phases of TNP. Blocking afferent signals with a tetrodotoxin (TTX)-ELVAX implanted immediately following nerve lesion suppressed the allodynia and rescued decision-making deficits. In contrast, the TTX used at a later phase could not suppress the allodynia nor rescue decision-making deficits. Intra-ACC administration of riluzole reduced the ACC neural sensitization but failed to restore ACC-BLA spike-field phase synchrony during the late stages of chronic neuropathic pain. Riluzole suppressed allodynia but failed to rescue the decision-making deficits during the late phase of TNP, suggesting that early pain relief is important for recovering from pain-related cognitive impairments. The functional disturbances in ACC neural circuitry may be relevant causes for the deficits in decision making in the chronic TNP state.

Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats

“…Although there is evidence of impaired myelination in human subjects with chronic visceral pain 6 and animal models of trigeminal neuropathic pain, 22 animal studies of myelin plasticity in chronic visceral hypersensitivity still lacking. We examined MBP, a biomarker for myelin basic protein, through immunohistochemistry.…”

“…The elevated levels of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, have been reported in patients suffering from chronic pain 20 and animal models of neuropathy pain. 22 To examine the neuroinflammatory reaction in response to chronic visceral hypersensitivity in our VH model, we performed immunohistochemistry to determine the relative expression of inflammatory cells (CD68 + cells, a biomarker for reactive microglia) and inflammatory cytokines (IL1β, a biomarker for inflammatory cytokine, interleukin 1) in the ACC ( Figure 3 A). A significant increase in the population of ameboid shaped CD68 + cells were observed in the ACC of VH rats, indicating an inflammatory reaction in the ACC of VH rats.…”

“… 19 The results of a recent study have shown increases in microglial activity and cytokine expression in chronic trigeminal neuropathy. 22 Microglia play a crucial role in neurodevelopment by interacting with neuronal cells such as OLs for wiring and neural circuit regulation. 23 Given that cumulative evidence of elevated levels of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, have been reported in patients suffering from chronic pain 20 , 24 and experimental animal models with pain, 17 , 21 and that oligodendroglia are markedly susceptible to inflammation-induced excitotoxicity in both rodents and humans, 25 , 26 in this study, we assess cytokines and microglial activity associated with hypomyelination in chronic visceral hypersensitivity rats.…”

Chemogenetic Activation of Astrocytes in the Basolateral Amygdala Contributes to Fear Memory Formation by Modulating the Amygdala–Prefrontal Cortex Communication

“…Data analyses, including spike sorting, spike-field coherence analysis, and analysis of phase locking of a single neuron to the theta oscillation were performed using a combination of tools in Matlab, Neuroexplorer, and Off-line Spike Sorter. Detailed procedures of multiple-channel recording of data and analyses have been described in our recent publications [ 10 , 27 , 28 , 29 ].…”

The cAMP Response Element- Binding Protein/Brain-Derived Neurotrophic Factor Pathway in Anterior Cingulate Cortex Regulates Neuropathic Pain and Anxiodepression Like Behaviors in Rats

“…Neuropathic pain results from damage or disease to the somatosensory nervous system, characterized by allodynia, hyperalgesia, and spontaneous pain ( Xu et al, 2021 ). At the same time, the transmission of long-term nociceptive signals induces plasticity changes in the structure and function of some brain regions such as the medial prefrontal cortex (mPFC) ( Mecca et al, 2021 ), ACC ( Smith et al, 2021 ), amygdala ( Murugappan et al, 2021 ), and hippocampus ( Toledo et al, 2021 ), which are also involved in the regulation of emotion and cognitive functions, so that nociceptive signals not only include pain components but also cover emotion-related components in the brain ( De Ridder et al, 2021 ). Clinical studies also point out that patients with neuropathic pain are often comorbid with disorders of emotional function ( Fonseca-Rodrigues et al, 2021 ), and patients with anxiety and depression often have allodynia and hyperalgesia ( Corlier et al, 2021 ), which exacerbates the vicious circle between pain and psychiatric disorders.…”