PMID- 22198556
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20211021
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 32
IP  - 6
DP  - 2012 Aug
TI  - Intracerebroventricular 4-methylcatechol (4-MC) ameliorates chronic pain 
      associated with depression-like behavior via induction of brain-derived 
      neurotrophic factor (BDNF).
PG  - 971-7
LID - 10.1007/s10571-011-9782-2 [doi]
AB  - Neuropathic pain concurrent with mood disorder from peripheral nerve injury is a 
      serious clinical problem that significantly affects quality of life. Recent 
      studies have suggested that a lack of brain-derived neurotrophic factor (BDNF) in 
      the limbic system may cause this pain-emotion. BDNF is induced in cultured 
      neurons by 4-methylcatechol (4-MC), but the role of 4-MC-induced BDNF in 
      pain-emotion is poorly understood. Thus, we assessed the possible involvement of 
      BDNF in brain in depression-like behavior during chronic pain following 
      peripheral nerve injury. In addition, we examined whether intracerebroventricular 
      (i.c.v.) 4-MC prevents chronic pain in rats and produces an antidepressant 
      effect. Sprague-Dawley rats implanted intracerebroventricularly with a PE-10 tube 
      were subjected to chronic constriction injury (CCI). Pain was assessed by a 
      reduction in paw withdrawal latency (PWL) to heat stimuli after CCI. We also used 
      a forced swimming testing (FST; time of immobility, in seconds) from day 14 to 
      day 21 after CCI. Modulation of pain and emotional behavior was performed by 
      injection of PD0325901 (a MEK1/2 inhibitor). 4-MC (100 nM) was continuously 
      administered i.c.v. for 3 days during the period from day 14 to day 21 after CCI. 
      To block analgesic and antidepressant effects, anti-BDNF antibody or K252a (a 
      TrkB receptor inhibitor) was injected in combination with 4-MC. Naloxone was also 
      coadministered to confirm the analgesic effect of 4-MC. During the chronic stage 
      after CCI, the rats showed a sustained decrease in PWL (thermal hyperalgesia) 
      associated with extension of the time of immobility (depression-like behavior). 
      PD0325901 significantly reduced the decrease in PWL and the increased time of 
      immobility after CCI. The decreased PWL and increased time of immobility were 
      also reduced by 4-MC and by treatment with an ERK1/2 inhibitor. These effects of 
      4-MC i.c.v. were reversed by anti-BDNF and K252a. The analgesic effect of 4-MC 
      i.c.v. was also antagonized by naloxone. Based on these results, we suggest that 
      a lack of BDNF and activation of ERK1/2 in the pain-emotion network in the CNS 
      may be involved in depression-like behavior during chronic pain. 4-MC i.c.v. 
      ameliorates chronic pain and depression-like behavior by producing of BDNF and 
      normalization of ERK1/2 activation. Therefore, enhancement of BDNF may be a new 
      treatment strategy for chronic pain associated with depression.
FAU - Fukuhara, Kayoko
AU  - Fukuhara K
AD  - Division of Neurosciences, Yamaguchi University Graduate School of Medicine, Ube, 
      Yamaguchi, Japan.
FAU - Ishikawa, Kozo
AU  - Ishikawa K
FAU - Yasuda, Seiko
AU  - Yasuda S
FAU - Kishishita, Yusuke
AU  - Kishishita Y
FAU - Kim, Hae-Kyu
AU  - Kim HK
FAU - Kakeda, Takahiro
AU  - Kakeda T
FAU - Yamamoto, Misa
AU  - Yamamoto M
FAU - Norii, Takafumi
AU  - Norii T
FAU - Ishikawa, Toshizo
AU  - Ishikawa T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111225
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Analgesics)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Benzamides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Catechols)
RN  - 12GLI7JGB3 (4-methylcatechol)
RN  - 86K0J5AK6M (mirdametinib)
RN  - 9N3CBB0BIQ (Diphenylamine)
SB  - IM
MH  - Analgesics/administration & dosage/pharmacology/therapeutic use
MH  - Animals
MH  - Antidepressive Agents/pharmacology/therapeutic use
MH  - *Behavior, Animal/drug effects
MH  - Benzamides/pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Catechols/*administration & dosage/pharmacology/*therapeutic use
MH  - Chronic Pain/*complications/*drug therapy
MH  - Depression/complications/*drug therapy
MH  - Diphenylamine/analogs & derivatives/pharmacology
MH  - Injections, Intraventricular
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reaction Time/drug effects
MH  - Restraint, Physical
EDAT- 2011/12/27 06:00
MHDA- 2012/11/14 06:00
CRDT- 2011/12/27 06:00
PHST- 2011/10/18 00:00 [received]
PHST- 2011/12/06 00:00 [accepted]
PHST- 2011/12/27 06:00 [entrez]
PHST- 2011/12/27 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
AID - 10.1007/s10571-011-9782-2 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2012 Aug;32(6):971-7. doi: 10.1007/s10571-011-9782-2. Epub 
      2011 Dec 25.