title: Spinal 5-HT1A, not the 5-HT1B or 5-HT3 receptors, mediates descending serotonergic inhibition for late-phase mechanical allodynia of carrageenan-induced peripheral inflammation.
abstract: Previous electrophysiological studies demonstrated a limited role of 5-hydroxytryptamine 3 receptor (5-HT3R), but facilitatory role of 5-HT1AR and 5-HT1BR in spinal nociceptive processing of carrageenan-induced inflammatory pain. The release of spinal 5-HT was shown to peak in early-phase and return to baseline in late-phase of carrageenan inflammation. We examined the role of the descending serotonergic projections involving 5-HT1AR, 5-HT1BR, and 5-HT3R in mechanical allodynia of early- (first 4h) and late-phase (24h after) carrageenan-induced inflammation. Intrathecal administration of 5-HT produced a significant anti-allodynic effect in late-phase, but not in early-phase. Similarly, intrathecal 5-HT1AR agonist (8-OH-DPAT) attenuated the intensity of late-phase allodynia in a dose dependent fashion which was antagonized by 5-HT1AR antagonist (WAY-100635), but produced no effect on the early-phase allodynia. However, other agonists or antagonists of 5-HT1BR (CP-93129, SB-224289) and 5-HT3R (m-CPBG, ondansetron) did not produce any anti- or pro-allodynic effect in both early- and late- phase allodynia. These results suggest that spinal 5-HT1A, but not 5-HT1B or 5-HT3 receptors mediate descending serotonergic inhibition on nociceptive processing of late-phase mechanical allodynia in carrageenan-induced inflammation.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea.
authors.forename: Joung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea.
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Jeong
authors.affiliation: Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea.
authors.forename: Seong Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Woon Mo
authors.initials: WM
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea.
authors.forename: Seongtae
authors.initials: S
authors.lastname: Jeong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hong Beom
authors.initials: HB
authors.lastname: Bae
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, Republic of Korea; Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address: jichoi@jnu.ac.kr.
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
mesh_terms: D000818:Animals; D002351:Carrageenan; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014110:Touch
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D002351:Carrageenan
keywords: 5-Hydroxytryptamine 1A receptor; Allodynia; Carrageenan; Serotonergic projection; Spinal cord