SKF96365 impedes spinal glutamatergic transmission-mediated neuropathic allodynia
Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Store-operated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic pla...
Saved in:
Published in | The Korean journal of physiology & pharmacology Vol. 27; no. 1; pp. 39 - 48 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English Korean |
Published |
Korea (South)
The Korean Physiological Society and The Korean Society of Pharmacology
01.01.2023
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Store-operated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED
of 18 μg. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 KISTI1.1003/JNL.JAKO202313737932879 Author contributions: Q.W. and Y.Z. were conducted in data interpretation, and manuscript writing. Q.D. and X.Z. were involved in the idea and data analysis. W.W., Q.Z., and M.X. were the principal author who contributed to the manuscript. |
ISSN: | 1226-4512 2093-3827 |
DOI: | 10.4196/kjpp.2023.27.1.39 |