잠시만 기다려 주세요. 로딩중입니다.

Systemically administered neurotensin receptor agonist produces antinociception through activation of spinally projecting serotonergic neurons in the rostral ventromedial medulla

Korean Journal of Pain 2021년 34권 1호 p.58 ~ 65
Li Yaqun, 강동호, 김웅모, 이형곤, 김승훈, 유현응, 최정일, 윤명하,
소속 상세정보
 ( Li Yaqun ) - Chonnam National University Medical School Chonnam National University Hospital Department of Anesthesiology and Pain Medicine
강동호 ( Kang Dong-Ho ) - Chonnam National University Medical School Chonnam National University Hospital Department of Anesthesiology and Pain Medicine
김웅모 ( Kim Woong-Mo ) - Chonnam National University Medical School Chonnam National University Hospital Department of Anesthesiology and Pain Medicine
이형곤 ( Lee Hyung-Gon ) - Chonnam National University Medical School Chonnam National University Hospital Department of Anesthesiology and Pain Medicine
김승훈 ( Kim Seung-Hoon ) - Chonnam National University Medical School Chonnam National University Hospital Department of Anesthesiology and Pain Medicine
유현응 ( You Hyun-Eung ) - Chonnam National University Hwasun Hospital Department of Anesthesiology and Pain Medicine
최정일 ( Choi Jeong-Il ) - Chonnam National University Medical School Chonnam National University Hospital Department of Anesthesiology and Pain Medicine
윤명하 ( Yoon Myung-Ha ) - Chonnam National University Medical School Chonnam National University Hospital Department of Anesthesiology and Pain Medicine

Abstract


Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism.

Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague?Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed.

Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine.

Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

키워드

Analgesia; Central Nervous System; Microdialysis; Neuralgia; Neurotensin; Rats; Receptors, Neurotensin; Serotonin; Spinal Cord

원문 및 링크아웃 정보

 

등재저널 정보