PMID- 26141984
OWN - NLM
STAT- MEDLINE
DCOM- 20151106
LR  - 20150824
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 136
DP  - 2015 Sep 1
TI  - Excitatory effect of Neurotropin((R)) on noradrenergic neurons in rat locus 
      coeruleus.
PG  - 79-86
LID - S0024-3205(15)00336-7 [pii]
LID - 10.1016/j.lfs.2015.06.013 [doi]
AB  - AIMS: Although the clinical use of Neurotropin(R) as an analgesic for chronic pain 
      has been firmly established, its analgesic mechanism is still unclear. In this 
      study, we investigate the direct effects of Neurotropin using an 
      electrophysiological method. MAIN METHODS: Blind patch-clamp recordings were made 
      from rat locus coeruleus (LC) and periaqueductal gray (PAG) neurons in brainstem 
      slices of normal rats. The effects of intracerebroventricular (icv) injection of 
      Neurotropin on nociceptive transmission were recorded from spinal substantia 
      gelatinosa (SG) neurons in fifth lumbar spinal nerve-ligated (L5-SNL) rats using 
      an in vivo patch-clamp method. KEY FINDINGS: Neurotropin (0.2-1.0 NU/mL) 
      dose-dependently increased the firing rate in noradrenergic LC neurons of normal 
      rats. Under the voltage-clamp condition, Neurotropin induced an inward current in 
      90% of LC neurons thatwas not affected by tetrodotoxin or an injection of GDP-beta-S 
      (G protein inhibitor) through recording pipettes. In contrast, Neurotropin had no 
      effects on all PAG neurons tested. Using in vivo patch-clamp recordings, the icv 
      injection of Neurotropin inhibited both frequency and amplitude of pinch-evoked 
      excitatory postsynaptic currents of SG neurons in L5-SNL rats. These results 
      suggest that Neurotropin directly excites the descending noradrenergic LC neurons 
      and inhibits nociceptive transmission in the spinal dorsal horn. SIGNIFICANCE: 
      This study is the first direct demonstration that Neurotropin activates the 
      noradrenergic descending pain inhibitory systems, and this would reinforce the 
      usefulness of Neurotropin in the treatment of human neuropathic pain.
FAU - Okai, Hisashi
AU  - Okai H
AD  - Department of Pharmacological Research, Institute of Bio-Active Science, Nippon 
      Zoki Pharmaceutical Co., Ltd., 442-1, Kinashi, Kato, Hyogo 673-1461, Japan. 
      Electronic address: h-okai@nippon-zoki.co.jp.
FAU - Okazaki, Ryohei
AU  - Okazaki R
AD  - Department of Pharmacological Research, Institute of Bio-Active Science, Nippon 
      Zoki Pharmaceutical Co., Ltd., 442-1, Kinashi, Kato, Hyogo 673-1461, Japan.
FAU - Kawamura, Minoru
AU  - Kawamura M
AD  - Department of Pharmacological Research, Institute of Bio-Active Science, Nippon 
      Zoki Pharmaceutical Co., Ltd., 442-1, Kinashi, Kato, Hyogo 673-1461, Japan.
FAU - Yoshimura, Megumu
AU  - Yoshimura M
AD  - Graduate School of Health Sciences, Kumamoto Health Science University, Kumamoto 
      861-5598, Japan.
LA  - eng
PT  - Journal Article
DEP - 20150702
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Analgesics)
RN  - 0 (Polysaccharides)
RN  - 57657-35-9 (neurotropin)
SB  - IM
MH  - Adrenergic Neurons/drug effects/*physiology
MH  - Analgesics/*administration & dosage
MH  - Animals
MH  - Drug Evaluation, Preclinical
MH  - Injections, Intraventricular
MH  - Locus Coeruleus/cytology/*drug effects
MH  - Male
MH  - Neuralgia/drug therapy
MH  - Nociception/drug effects
MH  - Patch-Clamp Techniques
MH  - Periaqueductal Gray/cytology/drug effects
MH  - Polysaccharides/*administration & dosage
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Descending pain inhibitory system
OT  - In vivo patch clamp
OT  - Locus coeruleus
OT  - Neuropathic pain
OT  - Neurotropin
OT  - Noradrenaline
EDAT- 2015/07/05 06:00
MHDA- 2015/11/07 06:00
CRDT- 2015/07/05 06:00
PHST- 2014/12/19 00:00 [received]
PHST- 2015/05/14 00:00 [revised]
PHST- 2015/06/04 00:00 [accepted]
PHST- 2015/07/05 06:00 [entrez]
PHST- 2015/07/05 06:00 [pubmed]
PHST- 2015/11/07 06:00 [medline]
AID - S0024-3205(15)00336-7 [pii]
AID - 10.1016/j.lfs.2015.06.013 [doi]
PST - ppublish
SO  - Life Sci. 2015 Sep 1;136:79-86. doi: 10.1016/j.lfs.2015.06.013. Epub 2015 Jul 2.