title: Synergistic antinociceptive effects of N-methyl-D-aspartate receptor antagonist and electroacupuncture in the complete Freund's adjuvant-induced pain model.
abstract: This study examined the synergistic antinociceptive effects associated with signaling pathway proteins of the spinal cord in a complete Freund's adjuvant (CFA)-induced pain model when electroacupuncture (EA) and a N-methyl-D-aspartate receptor (NMDAR) antagonist were administered in combination. EA stimulation (2 Hz, 1 mA) was needle-delivered for 20 min once daily at acupoints corresponding to Zusanli and Sanyinjiao with intrathecal injection of the NMDAR antagonist dizocilpine (MK801). Thermal sensitivity of the hindpaw induced by CFA was strongly inhibited by dizocilpine injection and EA stimulation. Co-treatment with EA and dizocilpine showed a synergistic antinociceptive effect against inflammatory pain. On day two of the experiment, we examined the phosphorylation of the NMDAR NR2B subunit, of the extracellular signal-regulated kinase (ERK), p38 and of the cAMP response element-binding protein (CREB) in the ipsilateral dorsal horn of L4-5 segments by Western blot analysis. Phosphorylation of the NMDAR NR2B subunit induced by CFA was markedly inhibited by co-treatment with dizocilpine and EA, but not by dizocilpine or EA treatment alone. CFA-induced phosphorylation of the ERK was inhibited by both dizocilpine and EA, but that of p38 was inhibited by EA only. CFA-induced phosphorylation of CREB was inhibited by dizocilpine, but did not show marked changes. Immunohistochemical analyses confirmed that there was a significant difference in the NMDAR NR2B subunit and ERK phosphorylation. It is possible that the combined treatment with EA and the NMDAR antagonist dizocilpine resulted in synergistic antinociceptive effects in an inflammatory pain model via the inactivation of both the NMDAR NR2B subunit and ERK of the spinal cord.
authors.affiliation: Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Jang
authors.forename: Ha-Neui
authors.initials: HN
authors.lastname: Kim
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Koo
authors.forename: Hwa-Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Eun-Sang
authors.initials: ES
authors.lastname: Choe
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D015671:Electroacupuncture; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005620:Freund's Adjuvant / Q000009:adverse effects*; D007150:Immunohistochemistry; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D005620:Freund's Adjuvant; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases