title: Acute single dose of ketamine relieves mechanical allodynia and consequent depression-like behaviors in a rat model.
abstract: Both chronic pain and depression are debilitating diseases, which often coexist in clinic. However, current analgesics and antidepressants exhibit limited efficacy for this comorbidity. The present study aimed to investigate the effect of ketamine on the comorbidity of inflammatory pain and consequent depression-like behaviors in a rat model established by intraplantar administration of complete Freunds adjuvant (CFA). The mechanical withdrawal threshold, thermal withdrawal latency, open field test, forced swimming test, and sucrose preference test were evaluated after the CFA injection and ketamine treatment. The hippocampus was harvested to determine the levels of interleukin (IL)-6, IL-1β, indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), 5-hydroxytryptamine (5-HT), and tryptophan (TRP). The inflammatory pain-induced depression-like behaviors presented on 7days and lasted to at least 14days after the CFA injection. Single dose of ketamine at 20mg/kg relieved both the mechanical allodynia and the associated depression-like behaviors as demonstrated by the attenuated mechanical withdrawal threshold, reduced immobility time in the forced swim test, and increased sucrose preference after ketamine treatment. The total distance had no significant change after the CFA injection or ketamine treatment in the open field test. Simultaneously, ketamine reduced the levels of IL-6, IL-1β, IDO, and KYN/TRP ratio and increased the 5-HT/TRP ratio in the hippocampus. In conclusion, acute single dose of ketamine can rapidly attenuate mechanical allodynia and consequent depression-like behaviors and down-regulate hippocampal proinflammatory responses and IDO/KYN signal pathway in rats.
authors: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors: Guang-Fen
authors: GF
authors: Zhang
authors: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China; Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors: Jing
authors: J
authors: Wang
authors: Jiangsu Province Key Laboratory of Anesthesiology, College of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
authors: Jin-Feng
authors: JF
authors: Han
authors: Department of Anesthesiology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, China.
authors: Jie
authors: J
authors: Guo
authors: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Jiangsu Province Key Laboratory of Anesthesiology, College of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
authors: Ze-Min
authors: ZM
authors: Xie
authors: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China; Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors: Wei
authors: W
authors: Pan
authors: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Jiangsu Province Key Laboratory of Anesthesiology, College of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
authors: Jian-Jun
authors: JJ
authors: Yang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, China. Electronic address: sunkangjiannw@163.com.
authors: Kang-Jian
authors: KJ
authors: Sun
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000150:complications / Q000517:prevention & control*; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D006624:Hippocampus / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007649:Ketamine / Q000008:administration & dosage*; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D059225:Nociception / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053583:Interleukin-1beta; D015850:Interleukin-6; D012701:Serotonin; D007737:Kynurenine; D007649:Ketamine; D014364:Tryptophan; D005620:Freund's Adjuvant
keywords: Cytokine; Depression-like behavior; Indoleamine 2, 3-dioxygenase; Ketamine; Pain