PMID- 24389017
OWN - NLM
STAT- MEDLINE
DCOM- 20141121
LR  - 20211021
IS  - 1528-8447 (Electronic)
IS  - 1526-5900 (Print)
IS  - 1526-5900 (Linking)
VI  - 15
IP  - 4
DP  - 2014 Apr
TI  - Ablating spinal NK1-bearing neurons eliminates the development of pain and 
      reduces spinal neuronal hyperexcitability and inflammation from mechanical joint 
      injury in the rat.
PG  - 378-86
LID - S1526-5900(13)01435-1 [pii]
LID - 10.1016/j.jpain.2013.12.003 [doi]
AB  - The facet joint is a common source of pain, especially from mechanical injury. 
      Although chronic pain is associated with altered spinal glial and neuronal 
      responses, the contribution of specific spinal cells to joint pain is not 
      understood. This study used the neurotoxin [Sar(9),Met(O2)(11)]-substance 
      P-saporin (SSP-SAP) to selectively eliminate spinal cells expressing neurokinin-1 
      receptor (NK1R) in a rat model of painful facet joint injury to determine the 
      role of those spinal neurons in pain from facet injury. Following spinal 
      administration of SSP-SAP or its control (blank-SAP), a cervical facet injury was 
      imposed and behavioral sensitivity was assessed. Spinal extracellular recordings 
      were made on day 7 to classify neurons and quantify evoked firing. Spinal glial 
      activation and interleukin 1alphaalpha (IL1alpha) expression also were evaluated. SSP-SAP 
      prevented the development of mechanical hyperalgesia that is induced by joint 
      injury and reduced NK1R expression and mechanically evoked neuronal firing in the 
      dorsal horn. SSP-SAP also prevented a shift toward wide dynamic range neurons 
      that is seen after injury. Spinal astrocytic activation and interleukin 1alpha (IL1alpha) 
      expression were reduced to sham levels with SSP-SAP treatment. These results 
      suggest that spinal NK1R-bearing cells are critical in initiating spinal 
      nociception and inflammation associated with a painful mechanical joint injury. 
      PERSPECTIVE: Results demonstrate that cells expressing NK1R in the spinal cord 
      are critical for the development of joint pain, spinal neuroplasticity, and 
      inflammation after trauma to the joint. These findings have utility for 
      understanding mechanisms of joint pain and developing potential targets to treat 
      pain.
CI  - Copyright (c) 2014 American Pain Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Weisshaar, Christine L
AU  - Weisshaar CL
AD  - Department of Bioengineering, University of Pennsylvania, Philadelphia, 
      Pennsylvania.
FAU - Winkelstein, Beth A
AU  - Winkelstein BA
AD  - Department of Bioengineering, University of Pennsylvania, Philadelphia, 
      Pennsylvania; Department of Neurosurgery, University of Pennsylvania, 
      Philadelphia, Pennsylvania. Electronic address: winkelst@seas.upenn.edu.
LA  - eng
GR  - R01 AR056288/AR/NIAMS NIH HHS/United States
GR  - AR 056288/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140102
PL  - United States
TA  - J Pain
JT  - The journal of pain
JID - 100898657
RN  - 0 (Receptors, Neurokinin-1)
SB  - IM
MH  - Animals
MH  - Arthralgia/metabolism
MH  - Central Nervous System Sensitization/physiology
MH  - Disease Models, Animal
MH  - Electrophysiology
MH  - Immunohistochemistry
MH  - Inflammation/*metabolism
MH  - Male
MH  - Neuroglia/metabolism
MH  - Neuronal Plasticity/physiology
MH  - Neurons/*metabolism
MH  - Pain/*metabolism
MH  - Posterior Horn Cells/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Neurokinin-1/*metabolism
MH  - Zygapophyseal Joint/*injuries
PMC - PMC3972292
MID - NIHMS553119
OTO - NOTNLM
OT  - Pain
OT  - joint
OT  - saporin
OT  - spinal cord
OT  - substance P
COIS- The authors declare no competing financial interests.
EDAT- 2014/01/07 06:00
MHDA- 2014/12/15 06:00
PMCR- 2015/04/01
CRDT- 2014/01/07 06:00
PHST- 2013/07/25 00:00 [received]
PHST- 2013/11/20 00:00 [revised]
PHST- 2013/12/18 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - S1526-5900(13)01435-1 [pii]
AID - 10.1016/j.jpain.2013.12.003 [doi]
PST - ppublish
SO  - J Pain. 2014 Apr;15(4):378-86. doi: 10.1016/j.jpain.2013.12.003. Epub 2014 Jan 2.