PMID- 20079735
OWN - NLM
STAT- MEDLINE
DCOM- 20100326
LR  - 20181201
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 222
IP  - 2
DP  - 2010 Apr
TI  - Depletion of spinal 5-HT accelerates mechanosensory recovery in the deafferented 
      rat spinal cord.
PG  - 277-84
LID - 10.1016/j.expneurol.2010.01.005 [doi]
AB  - Dorsal root injuries (DRIs), resulting in the permanent disconnection of nerve 
      roots from the spinal cord, lead to sensory impairments, including both the loss 
      of sensation and the development of neuropathic pain in the affected limb. DRI 
      results in axonal sprouting of intraspinal serotonergic fibers, but the 
      functional consequences of this response to spinal deafferentation remains 
      unclear. Here we aimed to clarify the role of descending serotonergic projections 
      in both mechanosensation and pain following DRI. By ablating serotonergic input 
      to the spinal cord via 5,7-dihydroxytryptamine (5,7-DHT) prior to DRI in rats, we 
      found that serotonergic input to the dorsal horn normally inhibits the recovery 
      of mechanosensation but has no effect on the development or resolution of cold 
      pain. Endogenous brain-derived neurotrophic factor (BDNF) is upregulated by 
      activated microglia, is required for sprouting of serotonergic axons and 
      neuropeptide tyrosine (NPY)-positive interneurons, and suppresses mechanosensory 
      recovery following DRI. Intriguingly, we found that the density of activated 
      microglia, the amount of BDNF protein, and density of NPY-positive processes were 
      all significantly reduced in 5,7-DHT-treated rats, suggesting that serotonergic 
      input to the deafferented dorsal horn is required for all of these consequences 
      of spinal deafferentation. These results indicate that BDNF-dependent 
      serotonergic and/or increases in NPY-positive fiber density slows, and ultimately 
      halts, mechanosensory recovery following DRI.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Cragg, J J
AU  - Cragg JJ
AD  - ICORD (International Collaboration on Repair Discoveries), Blusson Spinal Cord 
      Centre, Vancouver, BC, Canada V5Z 1M9.
FAU - Scott, A L
AU  - Scott AL
FAU - Ramer, M S
AU  - Ramer MS
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100115
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Lectins)
RN  - 0 (Neuropeptide Y)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc17a7 protein, mouse)
RN  - 0 (Vesicular Glutamate Transport Protein 1)
RN  - 31363-74-3 (5,7-Dihydroxytryptamine)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - 5,7-Dihydroxytryptamine/pharmacology
MH  - Animals
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Calcitonin Gene-Related Peptide/metabolism
MH  - Disease Models, Animal
MH  - Hyperalgesia/physiopathology
MH  - Hypesthesia/etiology/*physiopathology
MH  - Lectins/metabolism
MH  - Male
MH  - Microglia/metabolism
MH  - Neuropeptide Y/metabolism
MH  - Pain Threshold/drug effects/physiology
MH  - Peripheral Nervous System Diseases/complications/pathology
MH  - Physical Stimulation/methods
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function/*physiology
MH  - Rhizotomy/methods
MH  - Serotonin/*deficiency
MH  - Serotonin Agents/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Spinal Cord/*metabolism/pathology
MH  - Spinal Nerve Roots/injuries/metabolism/*physiopathology
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Up-Regulation/drug effects
MH  - Vesicular Glutamate Transport Protein 1/metabolism
EDAT- 2010/01/19 06:00
MHDA- 2010/03/27 06:00
CRDT- 2010/01/19 06:00
PHST- 2009/08/14 00:00 [received]
PHST- 2009/12/17 00:00 [revised]
PHST- 2010/01/07 00:00 [accepted]
PHST- 2010/01/19 06:00 [entrez]
PHST- 2010/01/19 06:00 [pubmed]
PHST- 2010/03/27 06:00 [medline]
AID - S0014-4886(10)00010-5 [pii]
AID - 10.1016/j.expneurol.2010.01.005 [doi]
PST - ppublish
SO  - Exp Neurol. 2010 Apr;222(2):277-84. doi: 10.1016/j.expneurol.2010.01.005. Epub 
      2010 Jan 15.