Next Article in Journal
Plastidial Expression of 3β-Hydroxysteroid Dehydrogenase and Progesterone 5β-Reductase Genes Confer Enhanced Salt Tolerance in Tobacco
Next Article in Special Issue
Synaptamide Improves Cognitive Functions and Neuronal Plasticity in Neuropathic Pain
Previous Article in Journal
Signal Transduction of Mineralocorticoid and Angiotensin II Receptors in the Central Control of Sodium Appetite: A Narrative Review
Previous Article in Special Issue
Inhibition of Spinal TRPV1 Reduces NMDA Receptor 2B Phosphorylation and Produces Anti-Nociceptive Effects in Mice with Inflammatory Pain
 
 
Article

The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats

1
Department of Physiology, Institute for Medical Science, Jeonbuk National University Medical School, Jeonju 54907, Korea
2
Department of Anesthesiology and Pain Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea
3
Department of Pet Animal, Division of Health and Life Science, Daejeon Institute of Science and Technology, Daejeon 35408, Korea
4
Department of Pharmacology, Institute for Medical Science, Jeonbuk National University Medical School, Jeonju 54907, Korea
*
Author to whom correspondence should be addressed.
These authors each contributed equally.
Academic Editors: Hee Young Kim, Bae Hwan Lee and Hee Kee Kim
Int. J. Mol. Sci. 2021, 22(21), 11730; https://doi.org/10.3390/ijms222111730
Received: 27 September 2021 / Revised: 25 October 2021 / Accepted: 28 October 2021 / Published: 29 October 2021
(This article belongs to the Special Issue Neuro-Plastic Mechanisms of Pain and Addiction)
Our recent study demonstrated that the CC-chemokine ligand 2 (CCL2) present in primary afferent fibers (PAFs) plays an important role in the microglia-dependent neuronal activation associated with zymosan-induced inflammatory pain. The present study was aimed to evaluate whether BD1047 (a prototypical sigma-1 receptor (Sig-1R) antagonist) is capable of modifying elevated levels of inflammation-evoked CCL2 as a peripheral antinociceptive mechanism. In DRG primary culture, zymosan dose-dependently increased CCL2 release from isolectin B4 (IB4)-positive DRG neurons, a process that was inhibited by co-culture with BD1047. Single treatment of BD1047 before intraplantar injection of zymosan in rats significantly reduced thermal hyperalgesia and mechanical hyperalgesia, as well as CCL2 expression in DRG neurons and microglia activation in the spinal dorsal horn. In the Complete Freund’s adjuvant (CFA)-induced inflammation model, repeated administration of BD1047 dramatically attenuated thermal hyperalgesia and mechanical hyperalgesia, and significantly diminished CCL2 immunoreactivity and microglia activation. Notably, CFA-induced inflammation significantly increased Sig-1R immunoreactivity in DRG neurons, which was co-localized with CCL2 and IB4, respectively. Taken together, our results suggest that BD1047′s anti-nociceptive property was substantially mediated by the inhibition of CCL2 release in unmyelinated PAFs and that this may, in turn, have attenuated the spinal microglia activation that is associated with inflammatory pain. View Full-Text
Keywords: CCL2; Complete Freund’s adjuvant; hyperalgesia; microglia; sigma-1 receptor CCL2; Complete Freund’s adjuvant; hyperalgesia; microglia; sigma-1 receptor
Show Figures

Figure 1

MDPI and ACS Style

Chun, S.; Lee, J.-H.; Yoon, S.-Y.; Kwon, Y.-B. The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats. Int. J. Mol. Sci. 2021, 22, 11730. https://doi.org/10.3390/ijms222111730

AMA Style

Chun S, Lee J-H, Yoon S-Y, Kwon Y-B. The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats. International Journal of Molecular Sciences. 2021; 22(21):11730. https://doi.org/10.3390/ijms222111730

Chicago/Turabian Style

Chun, Sungkun, Jun-Ho Lee, Seo-Yeon Yoon, and Young-Bae Kwon. 2021. "The Peripheral Role of CCL2 in the Anti-Nociceptive Effect of Sigma-1 Receptor Antagonist BD1047 on Inflammatory Hyperalgesia in Rats" International Journal of Molecular Sciences 22, no. 21: 11730. https://doi.org/10.3390/ijms222111730

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop