2. Academic Validation
  3. The BDNF-TrkB signaling pathway in the rostral anterior cingulate cortex is involved in the development of pain aversion in rats with bone cancer via NR2B and ERK-CREB signaling

The BDNF-TrkB signaling pathway in the rostral anterior cingulate cortex is involved in the development of pain aversion in rats with bone cancer via NR2B and ERK-CREB signaling

  • Brain Res Bull. 2022 Jul;185:18-27. doi: 10.1016/j.brainresbull.2022.04.001.
Jingjing Li 1,  Xu Wang 1,  Hong Wang 2,  Ruiwei Wang 1,  Yanjing Guo 1,  Lichi Xu 1,  Guangfen Zhang 1,  Jiangnan Wu 3,  Gongming Wang 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
  • 2 Department of Nephrology, Tai' an Central Hospital, Taian, Shandong 271000, China.
  • 3 Department of Anesthesiology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong 250021, China.
  • 4 Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China. Electronic address: [email protected].
PMID: 35398541 DOI: 10.1016/j.brainresbull.2022.04.001
Abstract

Patients with bone Cancer pain (BCP) are more prone to aversion. which not only causes mental distress but also aggravates BCP. However, the mechanism of BCP-related aversion is still unclear. Previous studies have demonstrated that the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway of the rostral anterior cingulate cortex (rACC) plays an important role in the regulation of emotions related to chronic pain, such as neuropathic pain or inflammatory pain; however, few studies have investigated the role of this pathway in Cancer pain. This study explored the role of BDNF in Cancer pain-related aversion in the rACC and to determine whether N-methyl D-aspartate receptor subtype 2B (NR2B) and extracellular signal-regulated kinase (ERK)-cAMP response element-binding (CREB) signaling are involved in Cancer pain-related aversion. A Sprague-Dawley rat model of BCP (one of the classic BCP models) was established, and the changes in pain aversion were detected by mechanical stimulation-induced conditioned place avoidance. Our findings confirmed that rats with BCP exhibited intense pain aversion accompanied by the up-regulated BDNF expression in the rACC. Additionally, the pain aversion of BCP rats was reduced while blocking the BDNF-TrkB. Furthermore, the expression of NR2B and phosphorylated ERK (PERK)/phosphorylated CREB (pCREB) were up-regulated with the development of pain aversion, whereas the use of NR2B blocker Ro25-6981, or ERK Inhibitor U0126 could reduce the pain aversion. The expression of NR2B and PERK/pCREB were up-regulated after exogenous BDNF was injected into the rACC, whereas the expression levels of NR2B and PERK/pCREB were down-regulated after blocking the BDNF-TrkB signaling. In conclusion, the BDNF-TrkB signaling in the rACC mediates the generation of aversion in rats with BCP, which requires the involvement of NR2B and the ERK-CREB signaling pathway.

Keywords

Brain-derived neurotrophic factor; CAMP response element binding; Cancer pain-related aversion; Extracellular signal-regulated kinase; N-methyl D-aspartate receptor subtype 2B; Rostral anterior cingulate cortex.

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