Abstract
Pain is the most common symptom reported by patients with rheumatoid arthritis (RA) even after the resolution of chronic joint inflammation. It is believed that RA-associated pain is not solely due to inflammation, but could also be attributed to aberrant modifications to the central nervous system. The P2X4 receptor (P2X4R) is an ATP-activated purinergic receptor that plays a significant role in the transmission of information in the nervous system and pain. The involvement of P2X4R during the pathogenesis of chronic inflammatory pain and neuropathic pain is well-established. The attenuation of this receptor alleviates disease pathogenesis and related symptoms, including hyperalgesia and allodynia. Although some studies have revealed the contribution of P2X4R in promoting joint inflammation in RA, how it implicates pain associated with RA at peripheral and central nervous systems is still lacking. In this review, the possible contributions of P2X4R in the nervous system and how it implicates pain transmission and responses were examined.
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Abbreviations
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor
- ASC:
-
PYD- and CARD-domain containing caspase-1
- ASIC:
-
Acid-sensing channel
- ADP:
-
Adenosine diphosphate
- ATP:
-
Adenosine triphosphate
- BDNF:
-
Brain-derived neurotrophin factor
- BDNF-TrKB:
-
BDNF-tyrosine kinase B
- BX430:
-
1-(2,6-Dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea
- Ca2+ :
-
Calcium ion
- CCI:
-
Chronic constriction injury
- CCL2:
-
Chemokine ligand 2
- CFA:
-
Complete Freund’s adjuvant
- CNS:
-
Central nervous system
- CORM-2:
-
Tricarbonyldichlororuthenium (II) dimer
- COX-2:
-
Cyclooxygenase-2
- CST:
-
Catestatin
- CXCL25:
-
ATP-mediated C-X-C motif chemokine-5
- DMARDs:
-
Disease-modifying anti-rheumatic drugs
- DRG:
-
Dorsal root ganglion
- ENaC:
-
Epithelial Na+ channel
- EPSPs:
-
Excitatory postsynaptic potentials
- ERK 1/2 :
-
Extracellular signal-regulated kinase 1/2
- GABAA :
-
ɣ-Aminobutyric acid A receptor
- GABAergic:
-
ɣ-Aminobutyric acidergic
- IFN-ɣ:
-
Interferon-ɣ
- IL-6:
-
Interleukin-6
- IL-17:
-
Interleukin-17
- IL-1β:
-
Interleukin-1β
- IRF5:
-
Interferon regulatory factor-5
- KCC2:
-
Potassium-chloride cotransporter
- K+ :
-
Potassium ion
- LTD:
-
Long-term depression
- LTP:
-
Long-term potentiation
- MMP-9:
-
Matrix metallopeptidase-9
- Na+ :
-
Sodium ion
- NLRP1:
-
Pyrin domain containing 1 of activated NLR family
- NMDAR:
-
N-Methyl-d-aspartate receptor
- NP-1815-PX:
-
(5-[3-(5-Thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1, 2-b][1,4]diazepine-2,4(3H,5H)-dione)
- PGs:
-
Prostaglandins
- PNI:
-
Peripheral nerve injury
- PPADs:
-
Pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid)
- P2X4R:
-
P2X4 receptor
- P2X7R:
-
P2X7 receptor
- P13K/Akt:
-
Phosphatidylinositol 3-kinase-protein kinase B
- p38 MAPK:
-
p38 Mitogen-activated protein kinase
- RA:
-
Rheumatoid arthritis
- TGF-β2:
-
Transforming growth factor-β2
- Th1:
-
T-helper cell 1
- TNF-α:
-
Tumor necrosis factor-α
- 5-BDBD:
-
5-(3-Bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one
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This study was funded by the Ministry of Higher Education, Malaysia and Universiti Sains Malaysia under Fundamental Research Grant Scheme (203.PPSP.6171238) and Short Term Grant (304/PPSP/6315333).
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Khir NAM and Ismail CAN developed the contents and wrote the manuscript, Noh ASM prepared illustrations and did the search strings and Shafin N proofread and ensured the relevant flow of the manuscript.
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Nurul Ajilah Mohamed Khir declares that she has no conflict of interest. Ain’ Sabreena Mohd Noh declares that she has no conflict of interest. Nazlahshaniza Shafin declares that she has no conflict of interest. Che Aishah Nazariah Ismail declares that she has no conflict of interest.
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Khir, N.A.M., Noh, A.S.M., Shafin, N. et al. Contribution of P2X4 receptor in pain associated with rheumatoid arthritis: a review. Purinergic Signalling 17, 201–213 (2021). https://doi.org/10.1007/s11302-021-09764-z
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DOI: https://doi.org/10.1007/s11302-021-09764-z