Genetic Enhancement of Neuropathic and Inflammatory Pain by Forebrain Upregulation of CREB-mediated Transcription
Overview
Affiliations
CREB has been reported to be activated by injury and is commonly used as marker for pain-related plasticity changes in somatosensory pathways, including spinal dorsal horn neurons and the anterior cingulate cortex (ACC). However no evidence has been reported to support the direct role of activated CREB in injury-related behavioral sensitization (or allodynia). Here we report that genetic enhancement of CREB-mediated transcription selectively in forebrain areas enhanced behavioral responses to non-noxious stimuli after chronic inflammation (CFA model) or nerve injury. In contrast, behavioral acute responses to peripheral subcutaneous injection of formalin did not show any significant difference. Furthermore, acute pain responses to noxious thermal stimuli were also not affected. Our results thus provide direct evidence that cortical CREB-mediated transcription contributes to behavioral allodynia in animal models of chronic inflammatory or neuropathic pain.
Zaheer F, Levine G, Simal A, Fatemi Tabatabaei S, Martino T, Descalzi G eNeuro. 2025; 12(2).
PMID: 39809538 PMC: 11794969. DOI: 10.1523/ENEURO.0244-24.2024.
Enhanced long-term potentiation in the anterior cingulate cortex of tree shrew.
Song Q, Li X, Lu J, Chen Q, Liu R, Zhou S Philos Trans R Soc Lond B Biol Sci. 2024; 379(1906):20230240.
PMID: 38853555 PMC: 11343311. DOI: 10.1098/rstb.2023.0240.
Wang Q, Qin F, Wang H, Yang H, Liu Q, Li Z Front Neurosci. 2021; 15:698967.
PMID: 34512242 PMC: 8431970. DOI: 10.3389/fnins.2021.698967.
Reactive Astrocytes: Critical Players in the Development of Chronic Pain.
Tang J, Bair M, Descalzi G Front Psychiatry. 2021; 12:682056.
PMID: 34122194 PMC: 8192827. DOI: 10.3389/fpsyt.2021.682056.
RGS4 Maintains Chronic Pain Symptoms in Rodent Models.
Avrampou K, Pryce K, Ramakrishnan A, Sakloth F, Gaspari S, Serafini R J Neurosci. 2019; 39(42):8291-8304.
PMID: 31308097 PMC: 6794935. DOI: 10.1523/JNEUROSCI.3154-18.2019.