title: Antinociceptive effects of endomorphin-2: suppression of substance P release in the inflammatory pain model rat.
abstract: Endomorphin-2 (EM2) and Substance P (SP) exert suppressive and facilitative influences upon nociception, respectively. Although EM2 and SP were often co-expressed in single neurons in dorsal root ganglion (DRG), it is still unknown if and how the nociception-suppressive influences of EM2 might be exerted upon nociception-facilitative effects of SP in the DRG neurons. We examined these issues in the inflammatory pain model rats produced by subcutaneous injection of the complete Freund's adjuvant into the hind paw. The paw withdrawal threshold for mechanical allodynia was measured. Changes of EM2 and SP release were estimated by measuring intrathecal levels of EM2 and SP through in vivo microdialysis analysis of cerebrospinal fluid. The mechanical allodynia was dose-dependently attenuated by intrathecal injection of EM2 or a neurokinin-1 receptor antagonist, and facilitated by intrathecal injection of SP or a mu-opioid receptor (MOR) antagonist. Importantly, intrathecal level of SP was found to be lowered by intrathecal injection of EM2. Morphologically, colocalization of EM2-, MOR- and SP-immunoreactivity in single DRG neurons was observed by immunofluorescent histochemistry, and co-expression of EM2 and SP in large, dense-cored presynaptic vesicles in primary afferents, as well as localization of MOR on pre- and postsynaptic membrane in spinal dorsal horn, was also confirmed electron miscroscopically. Thus, the results indicated that analgesic influences of EM2 upon inflammatory pain might be exerted through suppression of SP release, supporting the assumptions that binding of EM2 to presynaptic MOR might induce such effects.
authors: Department of Neurology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China; Department of Neurology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors: Xiao-Na
authors: XN
authors: Wu
authors: Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors: Tao
authors: T
authors: Zhang
authors: Department of Oncology Unit 2, PLA General Hospital, Beijing 100853, China.
authors: Nian-Song
authors: NS
authors: Qian
authors: Department of Neurosurgery, The 153th Hospital of PLA, Zhengzhou 450042, China.
authors: Xiao-Dong
authors: XD
authors: Guo
authors: Department of Neurology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors: Hong-Jun
authors: HJ
authors: Yang
authors: Department of Neurology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
authors: Kai-Bin
authors: KB
authors: Huang
authors: Department of Neurology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors: Gao-Quan
authors: GQ
authors: Luo
authors: Department of Neurology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China; Department of Neurology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors: Wei
authors: W
authors: Xiang
authors: Department of Neurology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
authors: Wen-Ting
authors: WT
authors: Deng
authors: Department of Oncology Unit 2, PLA General Hospital, Beijing 100853, China. Electronic address: daigh60@sohu.com.
authors: Guang-Hai
authors: GH
authors: Dai
authors: Department of Neurology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. Electronic address: 13889902718@139.com.
authors: Kai-Run
authors: KR
authors: Peng
authors: Department of Neurology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China. Electronic address: fimmuneurologypsy@163.com.
authors: Su-Yue
authors: SY
authors: Pan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D059350:Chronic Pain / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000503:physiopathology; D006930:Hyperalgesia / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D017551:Microdialysis; D008854:Microscopy, Electron; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology; D059225:Nociception / Q000502:physiology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology; D017661:Receptors, Presynaptic / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000503:physiopathology* / Q000648:ultrastructure; D066148:Spinal Cord Dorsal Horn / Q000503:physiopathology; D013314:Stress, Mechanical; D013373:Substance P / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D017661:Receptors, Presynaptic; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D013373:Substance P; C105294:endomorphin 2; D014364:Tryptophan
keywords: Analgesia; Electron microscopy; Microdialysis; Neuropeptide; Spinal cord