PMID- 32331300
OWN - NLM
STAT- MEDLINE
DCOM- 20210125
LR  - 20210125
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 8
DP  - 2020 Apr 22
TI  - Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an 
      Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization.
LID - 10.3390/ijms21082938 [doi]
LID - 2938
AB  - A large percentage of primary sensory neurons in the trigeminal ganglia (TG) 
      contain neuropeptides such as tachykinins or calcitonin gene-related peptide. 
      Neuropeptides released from the central terminals of primary afferents sensitize 
      the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but 
      also activate glial cells contributing to neuroinflammation and consequent 
      sensitization in chronic orofacial pain and migraine. In the present study, we 
      investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) 
      encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to 
      participate in inflammation and hyperalgesia in various models, but its role has 
      not been investigated in orofacial pain or headache. In the complete Freund's 
      adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 
      expression increased in the TG in response to inflammation. Duration-dependent 
      Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 
      was detected in both TG neurons and satellite glial cells (SGC) by the 
      ultrasensitive RNAscope in situ hybridization. We also compared gene expression 
      changes of selected neuronal and glial sensitization and neuroinflammation 
      markers between wild-type and Tac4-deficient (Tac4(-/-)) mice. Expression of the 
      SGC/astrocyte marker in the TG and TNC was significantly lower in intact and 
      saline/CFA-treated Tac4(-/-) mice. The procedural stress-related increase of the 
      SGC/astrocyte marker was also strongly attenuated in Tac4(-/)(-) mice. Analysis 
      of TG samples with a mouse neuroinflammation panel of 770 genes revealed that 
      regulation of microglia and cytotoxic cell-related genes were significantly 
      different in saline-treated Tac4(-/-) mice compared to their wild-types. It is 
      concluded that HK-1 may participate in neuron-glia interactions both under 
      physiological and inflammatory conditions and mediate pain in the trigeminal 
      system.
FAU - Aczel, Timea
AU  - Aczel T
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
FAU - Kecskes, Angela
AU  - Kecskes A
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
FAU - Kun, Jozsef
AU  - Kun J
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
AD  - Szentagothai Research Centre, Bioinformatics Research Group, Genomics and 
      Bioinformatics Core Facility, University of Pecs, H-7624 Pecs, Hungary.
FAU - Szenthe, Kalman
AU  - Szenthe K
AD  - Carlsbad Research Organization Ltd, H-9244 Ujronafo, Hungary.
FAU - Banati, Ferenc
AU  - Banati F
AUID- ORCID: 0000-0002-8999-523X
AD  - RT-Europe Ltd, H-9200 Mosonmagyarovar, Hungary.
FAU - Szathmary, Susan
AU  - Szathmary S
AD  - Galenbio Ltd, H-9200 Mosonmagyarovar, Hungary.
FAU - Herczeg, Robert
AU  - Herczeg R
AD  - Szentagothai Research Centre, Bioinformatics Research Group, Genomics and 
      Bioinformatics Core Facility, University of Pecs, H-7624 Pecs, Hungary.
FAU - Urban, Peter
AU  - Urban P
AD  - Szentagothai Research Centre, Bioinformatics Research Group, Genomics and 
      Bioinformatics Core Facility, University of Pecs, H-7624 Pecs, Hungary.
FAU - Gyenesei, Attila
AU  - Gyenesei A
AD  - Szentagothai Research Centre, Bioinformatics Research Group, Genomics and 
      Bioinformatics Core Facility, University of Pecs, H-7624 Pecs, Hungary.
FAU - Gaszner, Balazs
AU  - Gaszner B
AUID- ORCID: 0000-0003-2830-2732
AD  - Department of Anatomy, University of Pecs Medical School, H-7624 Pecs, Hungary.
FAU - Helyes, Zsuzsanna
AU  - Helyes Z
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
AD  - PharmInVivo Ltd., H-7629 Pecs, Hungary.
FAU - Bolcskei, Kata
AU  - Bolcskei K
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
LA  - eng
GR  - National Brain Research Program 2017-1.2.1-NKP-2017-00002/Government of Hungary/
GR  - GINOP-2.3.2-15-2016-00050/Government of Hungary/
GR  - EFOP 3.6.2-17-2017-00008/Government of Hungary/
GR  - EFOP-3.6.1-16-2016-00004/Government of Hungary/
GR  - NTP-NFTO-18-B-0455/Goverment of Hungary/
GR  - OTKA FK132587/National Research, Development and Innovation Office of Hungary/
PT  - Journal Article
DEP - 20200422
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (Tachykinins)
RN  - 0 (hemokinin-1)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Facial Pain/*etiology/metabolism/physiopathology
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Hyperalgesia
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neuroglia/metabolism
MH  - Sensory Receptor Cells/metabolism
MH  - Tachykinins/*genetics/metabolism
MH  - Trigeminal Ganglion/*metabolism
MH  - Trigeminal Neuralgia/etiology/metabolism
PMC - PMC7215309
OTO - NOTNLM
OT  - complete Freund's adjuvant
OT  - hemokinin-1
OT  - macrophages
OT  - neuroinflammation
OT  - orofacial pain
OT  - satellite glial cells
OT  - trigeminal ganglia
COIS- Kalman Szenthe is the head of laboratory of Carlsbad Research Organization Ltd. 
      The company participated in the study within the frame of a cooperation, there is 
      no conflict of interest and financial relationship with the present work. Ferenc 
      Banati is the head of laboratory of the RT-Europe Ltd. The company participated 
      in the study within the frame of a cooperation, there is no conflict of interest 
      and financial relationship with the present work. Susan Szathmary is the 
      scientific director of the Galenbio Ltd. The company participated in the study 
      within the frame of a cooperation, there is no conflict of interest and financial 
      relationship with the present work. Zsuzsanna Helyes is the scientific director 
      and shareholder of PharmInVivo, there is no conflict of interest and financial 
      relationship with the present work; the company did not play any role in the 
      paper.
EDAT- 2020/04/26 06:00
MHDA- 2021/01/26 06:00
PMCR- 2020/04/01
CRDT- 2020/04/26 06:00
PHST- 2020/03/27 00:00 [received]
PHST- 2020/04/12 00:00 [revised]
PHST- 2020/04/19 00:00 [accepted]
PHST- 2020/04/26 06:00 [entrez]
PHST- 2020/04/26 06:00 [pubmed]
PHST- 2021/01/26 06:00 [medline]
PHST- 2020/04/01 00:00 [pmc-release]
AID - ijms21082938 [pii]
AID - ijms-21-02938 [pii]
AID - 10.3390/ijms21082938 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Apr 22;21(8):2938. doi: 10.3390/ijms21082938.