PMID- 29523370
OWN - NLM
STAT- MEDLINE
DCOM- 20200422
LR  - 20240201
IS  - 1879-1271 (Electronic)
IS  - 0268-0033 (Print)
IS  - 0268-0033 (Linking)
VI  - 64
DP  - 2019 Apr
TI  - Physiologic facet capsule stretch can induce pain & upregulate matrix 
      metalloproteinase-3 in the dorsal root ganglia when preceded by a physiological 
      mechanical or nonpainful chemical exposure.
PG  - 122-130
LID - S0268-0033(18)30028-7 [pii]
LID - 10.1016/j.clinbiomech.2018.01.009 [doi]
AB  - BACKGROUND: Neck pain from cervical facet loading is common and induces 
      inflammation and upregulation of nerve growth factor (NGF) that can sensitize the 
      joint afferents. Yet, the mechanisms by which these occur and whether afferents 
      can be pre-conditioned by certain nonpainful stimuli are unknown. This study 
      tested the hypothesis that a nonpainful mechanical or chemical insult predisposes 
      a facet joint to generate pain after a later exposure to typically nonpainful 
      distraction. METHODS: Rats were exposed to either a nonpainful distraction or an 
      intra-articular subthreshold dose of NGF followed by a nonpainful distraction two 
      days later. Mechanical hyperalgesia was measured daily and C6 dorsal root ganglia 
      (DRG) tissue was assayed for NGF and matrix metalloproteinase-3 (MMP-3) 
      expression on day 7. FINDINGS: The second distraction increased joint 
      displacement and strains compared to its first application (p = 0.0011). None of 
      the initial exposures altered behavioral sensitivity in either of the groups 
      being pre-conditioned or in controls; but, sensitivity was established in both 
      groups receiving a second distraction within one day that lasted until day 7 
      (p < 0.024). NGF expression in the DRG was increased in both groups undergoing a 
      pre-conditioning exposure (p < 0.0232). Similar findings were observed for MMP-3 
      expression, with a pre-conditioning exposure increasing levels after an otherwise 
      nonpainful facet distraction. INTERPRETATION: These findings suggest that 
      nonpainful insults to the facet joint, when combined, can generate painful 
      outcomes, possibly mediated by upregulation of MMP-3 and mature NGF.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Singh, Sagar
AU  - Singh S
AD  - Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 
      Skirkanich Hall, Philadelphia, PA 19104, USA.
FAU - Kartha, Sonia
AU  - Kartha S
AD  - Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 
      Skirkanich Hall, Philadelphia, PA 19104, USA.
FAU - Bulka, Ben A
AU  - Bulka BA
AD  - Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 
      Skirkanich Hall, Philadelphia, PA 19104, USA.
FAU - Stiansen, Nicholas S
AU  - Stiansen NS
AD  - Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 
      Skirkanich Hall, Philadelphia, PA 19104, USA.
FAU - Winkelstein, Beth A
AU  - Winkelstein BA
AD  - Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 
      Skirkanich Hall, Philadelphia, PA 19104, USA; Department of Neurosurgery, 
      University of Pennsylvania, 210 S. 33rd Street, 240 Skirkanich Hall, 
      Philadelphia, PA 19104, USA. Electronic address: winkelst@seas.upenn.edu.
LA  - eng
GR  - R01 AR056288/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180131
PL  - England
TA  - Clin Biomech (Bristol, Avon)
JT  - Clinical biomechanics (Bristol, Avon)
JID - 8611877
RN  - 0 (Ngf protein, rat)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Ganglia, Spinal/*metabolism
MH  - Gene Expression Regulation, Enzymologic
MH  - Hyperalgesia/metabolism/*physiopathology
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Nerve Growth Factor/*metabolism
MH  - Pain
MH  - Pain Measurement
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Up-Regulation
MH  - Zygapophyseal Joint/physiopathology
PMC - PMC6067996
MID - NIHMS948838
OTO - NOTNLM
OT  - Biomechanics
OT  - Facet joint
OT  - Injury
OT  - Matrix metalloproteinase
OT  - Neck pain
OT  - Nerve growth factor
COIS- Conflicts of Interest: The authors have no financial relationships to disclose.
EDAT- 2018/03/11 06:00
MHDA- 2020/04/23 06:00
PMCR- 2020/04/01
CRDT- 2018/03/11 06:00
PHST- 2017/09/12 00:00 [received]
PHST- 2017/12/22 00:00 [revised]
PHST- 2018/01/15 00:00 [accepted]
PHST- 2018/03/11 06:00 [pubmed]
PHST- 2020/04/23 06:00 [medline]
PHST- 2018/03/11 06:00 [entrez]
PHST- 2020/04/01 00:00 [pmc-release]
AID - S0268-0033(18)30028-7 [pii]
AID - 10.1016/j.clinbiomech.2018.01.009 [doi]
PST - ppublish
SO  - Clin Biomech (Bristol, Avon). 2019 Apr;64:122-130. doi: 
      10.1016/j.clinbiomech.2018.01.009. Epub 2018 Jan 31.