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: Kozo Ishikawa, Seiko Yasuda, Kayoko Fukuhara, Yasutake Iwanaga, Yuika Ida, Junko Ishikawa, Hirotaka Yamagata, Midori Ono, Takahiro Kakeda, Toshizo Ishikawa
• Journal: Neuroreport (Neuroreport) Vol. 25 Issue 4 Pg. 226-32 (Mar 05 2014) ISSN: 1473-558X [Electronic] England
• PMID: 24518228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Antidepressive Agents
• Brain-Derived Neurotrophic Factor
• Catechols
• RNA, Messenger
• 4-methylcatechol
• Receptor, trkB
• Extracellular Signal-Regulated MAP Kinases

Topics

• Analgesics (therapeutic use)
• Animals
• Antidepressive Agents (therapeutic use)
• Brain (drug effects, metabolism)
• Brain-Derived Neurotrophic Factor (metabolism)
• Catechols (therapeutic use)
• Chronic Pain (complications, drug therapy, metabolism)
• Depression (complications, drug therapy, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gyrus Cinguli (drug effects, metabolism)
• Hot Temperature
• Hyperalgesia (complications, drug therapy, metabolism)
• Nerve Compression Syndromes
• Neuropsychological Tests
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptor, trkB (antagonists & inhibitors, metabolism)
• Sciatic Nerve
• Signal Transduction (drug effects)