Substance P Mediates Estrogen Modulation Proinflammatory Cytokines Release in Intervertebral Disc
- PDF / 1,513,537 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 9 Downloads / 157 Views
ORIGINAL ARTICLE
Substance P Mediates Estrogen Modulation Proinflammatory Cytokines Release in Intervertebral Disc Xiao-Xing Song,1 Lin-Yu Jin,2 Xin-Feng Li ,3,4 Yan Luo,1 and Bu-Wei Yu1,4 Received 8 May 2020; accepted 16 September 2020
Intervertebral disc degeneration (IDD) is a main contributor to low back pain. A close relationship exists between inflammation and pain. Estrogen can affect inflammation and may play a crucial role in IDD and pain. Substance P (SP) can also regulate the expression of pro-inflammatory cytokines in intervertebral disc (IVD). This study aimed to investigate the potential role of SP in estrogen regulation of IDD. Nine-week-old C57BL/6 female mice were divided into four groups as follows: sham surgery (sham), ovariectomy (OVX), ovariectomy plus estrogen replacement therapy (ERT) group (OVX+E2), and ovariectomy, ERT plus neurokinin 1 receptor (NK1R) agonist (OVX+E2+G). Serum E2, body, and uterus weight were recorded. Immunohistochemistry study and quantitative real-time PCR were used for SP, NK1R, IL-1β, IL-6, and TNF-α examination and comparison in IVD at protein and gene levels. After OVX, the gene and protein expression of TNF-α, IL-1β, IL-6, SP, and NK1R in NP cells significantly increased compared with the sham group. ERT can reverse these impacts. ERT plays anti-inflammatory and anti-hyperalgesic roles in IDD of OVX mice. The estrogen-induced changes of the pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, are significantly inhibited by NK1R agonists. SP may be a mediator of estrogen regulating pro-inflammatory factors in IDD. Estrogen may affect IVD inflammation through two ways: one is to directly affect the level of pro-inflammatory cytokines and the other is by means of modulation of SP. Abstract—
KEY WORDS: discogenic pain; estrogen; inflammation; intervertebral disk; ovariectomy; substance P.
Xiao-Xing Song and Lin-Yu Jin are co-first authors 1
Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Lu, Shanghai, 200025, China 2 Department of Spinal Surgery, Peking University People’s Hospital, Peking University, Beijing, 100044, China 3 Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630, Dongfang Rd, Shanghai, 200127, People’s Republic of China 4 To whom correspondence should be addressed to Xin-Feng Li at Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630, Dongfang Rd, Shanghai, 200127, People’s Republic of China. E-mail: [email protected]; and ; [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Song, Jin, Li, Luo, and Yu INTRODUCTION Chronic low back pain is the most common chronic pain in the world [2]. Intervertebral disc (IVD) degeneration (IDD) is a major cause of low back pain [10]. The pathogenesis of discogenic pain is a complex pathological process regulated by many factors [10]. Estrogen may play a crucial effect in IDD and pain, as w
Data Loading...
