title: 4-Methylcatechol prevents derangements of brain-derived neurotrophic factor and TrkB-related signaling in anterior cingulate cortex in chronic pain with depression-like behavior.
abstract: Chronic pain with mood disorder, resulting from a peripheral nerve injury, is a serious clinical problem affecting the quality of life. A lack of brain-derived neurotrophic factor (BDNF) and abnormal intercellular signaling in the brain can mediate this symptom. BDNF is induced in cultured neurons by 4-methylcatechol (4-MC), but little is known about its role in pain-emotion. Thus, we characterized the actions of 4-MC on TrkB receptor-related pERK and BDNF mRNA in discreet brain regions related to pain-emotion after chronic pain in rat. Rats implanted with a stainless steel cannula into the lateral ventricular were subjected to chronic constriction injury (CCI). Pain was assessed by changes in paw withdrawal latency (PWL) to heat stimuli after CCI. Immobility time during the forced swimming testing was measured for depression-like behavior. Analgesic and antidepression modulations with 4-MC were examined by an anti-BDNF antibody (K252a, a TrkB receptor inhibitor). The animals were perfused and fixed (4% paraformaldehyde) for immunohistochemistry analysis (c-FOS/pERK). BDNF mRNA expression (anterior cingulate cortex) was determined using reverse transcription-PCR. Rats showed a sustained decrease in PWL, associated with a prolonged immobility time after CCI. 4-MC reduced decreases in PWL and increased immobility time. 4-MC reduced increases in pERK immunoreactivity and decreases in BDNF mRNA expression in regions related to pain and the limbic system. Anti-BDNF blocked effects induced by 4-MC. We suggest that a lack of BDNF associated with activated extracellular signal-regulated kinase in the pain-emotion network may be involved in depression-like behavior during chronic pain. 4-MC ameliorates pain-emotion symptoms by inducing BDNF and normalizing pERK activities.
authors: aDepartment of Laboratory Sciences, Division of Neurosciences Departments of bNeurosciences cPsychology, Yamaguchi University Graduate School of Medicine dDepartment of Food and Nutrition, Ube Frontier College, Yamaguchi eDepartment of 2nd Anatomy, Sapporo Medical University, Sapporo fDepartment of Nursing, Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Japan.
authors: Kozo
authors: K
authors: Ishikawa
authors: Seiko
authors: S
authors: Yasuda
authors: Kayoko
authors: K
authors: Fukuhara
authors: Yasutake
authors: Y
authors: Iwanaga
authors: Yuika
authors: Y
authors: Ida
authors: Junko
authors: J
authors: Ishikawa
authors: Hirotaka
authors: H
authors: Yamagata
authors: Midori
authors: M
authors: Ono
authors: Takahiro
authors: T
authors: Kakeda
authors: Toshizo
authors: T
authors: Ishikawa
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002396:Catechols / Q000627:therapeutic use*; D059350:Chronic Pain / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D009408:Nerve Compression Syndromes; D009483:Neuropsychological Tests; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D012584:Sciatic Nerve; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000700:Analgesics; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002396:Catechols; D012333:RNA, Messenger; C018599:4-methylcatechol; D020813:Receptor, trkB; D048049:Extracellular Signal-Regulated MAP Kinases