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

2021 ◽  
Vol 22 (21) ◽  
pp. 11730
Author(s):  
Sungkun Chun ◽  
Jun-Ho Lee ◽  
Seo-Yeon Yoon ◽  
Young-Bae Kwon
Keyword(s):  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Repeated Administration ◽  
Microglia Activation ◽  
Mechanical Hyperalgesia ◽  
Drg Neurons ◽  
Intraplantar Injection ◽  
Sigma 1 Receptor ◽  
Sigma 1 ◽  
Isolectin B4

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.

scholarly journals Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chun-Ping Huang ◽  
Hsiang-Ni Chen ◽  
Hong-Lin Su ◽  
Ching-Liang Hsieh ◽  
Wei-Hsin Chen ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Dorsal Root Ganglia ◽  
Inflammatory Pain ◽  
Dorsal Root ◽  
Low Frequency ◽  
Thermal Hyperalgesia ◽  
Nerve Fibers ◽  
Drg Neurons ◽  
Plantar Surface ◽  
Voltage Gated Sodium Channels

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

Antihypernociceptive and antioxidant effects of Petersianthus macrocarpus stem bark extracts in rats with complete Freund’s adjuvant-induced persistent inflammatory pain

2017 ◽  
Vol 14 (2) ◽  
Author(s):  
Francis Desire Tatsinkou Bomba ◽  
Bibiane Aimée Wandji ◽  
Christian Kuete Fofié ◽  
Albert Kamanyi ◽  
Télesphore Benoit Nguelefack
Keyword(s):  
Spinal Cord ◽  
Inflammatory Pain ◽  
Folk Medicine ◽  
Antioxidant Properties ◽  
Stem Bark ◽  
Oral Route ◽  
Mechanical Hyperalgesia ◽  
Intraplantar Injection ◽  
Field Device ◽  
The Brain

AbstractBackground(P. Beauv.) Liben (Lecythidaceae) is a plant used in Cameroonian folk medicine to cure ailments such as inflammation and pain. Previous work showed that aqueous (AEPM) and methanol (MEPM) extracts from the stem bark ofMethodsInflammatory pain was induced by intraplantar injection of CFA into the left hind paw of Wistar rats. AEPM and MEPM were administered either acutely or chronically by the oral route at the doses of 100 and 200 mg/kg/day. The mechanical hyperalgesia was tested using an analgesimeter, while the locomotion activity at the end of experiment was evaluated with an open-field device. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) contents were assayed in the brain and spinal cord of rats subjected to 14 days chronic treatment.ResultsAEPM and MEPM at both doses significantly (p<0.001) inhibited the acute and chronic mechanical hyperalgesia induced by CFA. Although not significant, both extracts increased the mobility of CFA-injected animals. AEPM significantly (p<0.01) reduced the level of nitrate at 100 mg/kg, MDA at 200 mg/kg and significantly (p<0.05) increased the SOD in the spinal cord. MEPM significantly increased the SOD content and reduced the MDA concentration in the brain but had no effect on the nitrate.ConclusionsAEPM and MEPM exhibit acute and chronic antihyperalgesic activities. In addition, both extracts possess antioxidant properties that might strengthen their chronic antihyperalgesic effects.

Antinociceptive, anti-inflammatory and antioxidant effects of Boerhavia coccinea extracts and fractions on acute and persistent inflammatory pain models

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Basile Nganmegne Piegang ◽  
Fabrice Sterlin Tchantchou Ndjateu ◽  
Mathieu Tene ◽  
Francis Désiré Tatsinkou Bomba ◽  
Pius Pum Tseuguem ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Inflammatory Pain ◽  
Chronic Treatment ◽  
Antinociceptive Effect ◽  
Repeated Administration ◽  
No Production ◽  
Herbaceous Plant ◽  
Intraplantar Injection ◽  
Anti Inflammatory ◽  
Antioxidant Effects

AbstractBackgroundBoerhavia coccinea (Nyctaginaceae) is an herbaceous plant used for the treatment of pain. The aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of the aqueous (AEBC) and ethanol (EEBC) extracts of Boerhavia coccinea as well as the major fractions (F1, F2 and F3) from EEBC.MethodsThe antinociceptive effect of the extracts and fractions was evaluated using formalin test. AEBC, EEBC and F1 were selected and further evaluated acutely (24 h) and chronically (16 days) in Complete Freund’s Adjuvant (CFA)-induced persistent inflammatory pain for their antihyperalgesic and anti-inflammatory effects. They were administered orally (100 and 200 mg/kg/day) from 48 h following the intraplantar injection of 100 µL of CFA. After the 16 days of chronic treatment, rats’ spinal cord and brain were collected for the evaluation of oxidative stress parameters namely nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT).ResultsAEBC, EEBC and F1 significantly inhibited the first and second phases of the formalin-induced pain. They significantly reduced the hyperalgesia both in acute and chronic treatments. These extracts showed no acute anti-inflammatory effect. AEBC and EEBC exhibited anti-inflammatory activities after repeated administration. AEBC, EEBC and F1 significantly reduced MDA level and significantly increased SOD and catalase activities, mainly in the spinal cord. AEBC and EEBC also reduced the NO production in the spinal cord.ConclusionsBoerhavia coccinea extracts and F1 possess potent antinociceptive activity which is not related to their anti-inflammatory properties. Their antioxidant effects may contribute to these activities in chronic treatment.

scholarly journals Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain

2021 ◽  
Vol 22 (4) ◽  
pp. 1967
Author(s):  
Alessio Ardizzone ◽  
Roberta Fusco ◽  
Giovanna Casili ◽  
Marika Lanza ◽  
Daniela Impellizzeri ◽  
...  
Keyword(s):  
Oral Administration ◽  
Inflammatory Pain ◽  
Acid Amide ◽  
Thermal Hyperalgesia ◽  
Inflammatory Cells ◽  
Intraplantar Injection ◽  
Metabotropic Glutamate ◽  
Rate Of Dissolution ◽  
Anti Inflammatory ◽  
Rat Paw

Palmitoylethanolamide (PEA), a fatty acid amide, has been widely investigated for its analgesic and anti-inflammatory properties. The ultra-micronized formulation of PEA (um-PEA), that has an enhanced rate of dissolution, is extensively used. Acetyl-l-carnitine (LAC), employed for the treatment of neuropathic pain in humans, is able to cause analgesia by up-regulating type-2 metabotropic glutamate (mGlu2) receptors. In the present study, we tested different associations of um-PEA, LAC and non-micronized PEA (non-m-PEA) in a rat model of carrageenan (CAR)-induced paw edema. Intraplantar injection of CAR into the hind paw of animals caused edema, thermal hyperalgesia, accumulation of infiltrating inflammatory cells and augmented myeloperoxidase (MPO) activity. All these parameters were decreased in a significantly manner by oral administration of a compound constituted by a mixture of um-PEA and LAC in relation 1:1 (5 mg/kg), but not with the association of single compounds administered one after the other. These findings showed the superior anti-inflammatory and anti-nociceptive action displayed by oral administration of um-PEA and LAC versus LAC plus, separate but consecutive, um-PEA in the rat paw CAR model of inflammatory pain.

scholarly journals Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Catia C. F. Bernardy ◽  
Ana C. Zarpelon ◽  
Felipe A. Pinho-Ribeiro ◽  
Cássia Calixto-Campos ◽  
Thacyana T. Carvalho ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Superoxide Dismutase ◽  
Mrna Expression ◽  
Inflammatory Pain ◽  
Superoxide Anion ◽  
Thermal Hyperalgesia ◽  
Mechanical Hyperalgesia ◽  
Antioxidant Defenses ◽  
Paw Edema ◽  
Anti Inflammatory

The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10–100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91phox, Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO2-induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.

scholarly journals Persistent pain model reveals sex difference in morphine potency

2006 ◽  
Vol 291 (2) ◽  
pp. R300-R306 ◽  
Author(s):  
Xiaoya Wang ◽  
Richard J. Traub ◽  
Anne Z. Murphy
Keyword(s):  
Inflammatory Pain ◽  
Opiate Receptors ◽  
Thermal Hyperalgesia ◽  
Tail Flick ◽  
Significant Shift ◽  
Sprague Dawley ◽  
Intraplantar Injection ◽  
Intact Male ◽  
Hot Plate Test ◽  
Before And After

Central or systemic administration of agonists directed at the μ or δ opiate receptors generally produce a greater degree of analgesia in males than in females. To date, most studies examining sex-based differences in opioid analgesia have used acute noxious stimuli (i.e., tail-flick and hot plate test); thus the potential dimorphic response of centrally acting opiates in the alleviation of persistent inflammatory pain is not well established. In the present study, right hind paw withdrawal latency (PWL) to radiant thermal stimuli was measured in intact male and cycling female Sprague-Dawley rats before and after unilateral hind paw injection of the inflammatory agent complete Freund's adjuvant (CFA). Control animals received intraplantar injection of saline. Twenty four hours after CFA or saline injection, animals received either saline or morphine bisulfate (0.5–15 mg/kg sc). Separate groups of control or inflamed animals were tested on their responsiveness to morphine at 7, 14, and 21 days post-CFA or saline. No sex differences were noted for baseline PWLs, and females displayed slightly less thermal hyperalgesia at 24 h post-CFA. At all morphine doses administered, both the antihyperalgesic effects of morphine in the inflamed animals and the antinociceptive effects of morphine in control animals were significantly greater in males compared with females. Similarly, in males, the antihyperalgesic effects of morphine increased significantly at 7–21 days post-CFA; no significant shift in morphine potency was noted for females. These studies demonstrate sex-based differences in the effects of morphine on thermal hyperalgesia in a model of persistent inflammatory pain.

scholarly journals Sigma‐1 Receptor Expression in DRG Neurons During a Carrageenan‐Provoked Inflammation

2019 ◽  
Vol 302 (9) ◽  
pp. 1620-1627 ◽  
Author(s):  
Leo Jerčić ◽  
Sandra Kostić ◽  
Marija Vitlov Uljević ◽  
Tanja Vukušić Pušić ◽  
Katarina Vukojević ◽  
...  
Keyword(s):  
Receptor Expression ◽  
Drg Neurons ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals Inhibition of Spinal TRPV1 Reduces NMDA Receptor 2B Phosphorylation and Produces Anti-Nociceptive Effects in Mice with Inflammatory Pain

2021 ◽  
Vol 22 (20) ◽  
pp. 11177
Author(s):  
Suk-Yun Kang ◽  
Su Yeon Seo ◽  
Se Kyun Bang ◽  
Seong Jin Cho ◽  
Kwang-Ho Choi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Intraplantar Injection ◽  
Analgesic Effects

Transient receptor potential vanilloid 1 (TRPV1) has been implicated in peripheral inflammation and is a mediator of the inflammatory response to various noxious stimuli. However, the interaction between TRPV1 and N-methyl-D-aspartate (NMDA) receptors in the regulation of inflammatory pain remains poorly understood. This study aimed to investigate the analgesic effects of intrathecal administration of capsazepine, a TRPV1 antagonist, on carrageenan-induced inflammatory pain in mice and to identify its interactions with NMDA receptors. Inflammatory pain was induced by intraplantar injection of 2% carrageenan in male ICR mice. To investigate the analgesic effects of capsazepine, pain-related behaviors were evaluated using von Frey filaments and a thermal stimulator placed on the hind paw. TRPV1 expression and NMDA receptor phosphorylation in the spinal cord and glutamate concentration in the spinal cord and serum were measured. Intrathecal treatment with capsazepine significantly attenuated carrageenan-induced mechanical allodynia and thermal hyperalgesia. Moreover, carrageenan-enhanced glutamate and phosphorylation of NMDA receptor subunit 2B in the spinal cord were suppressed by capsazepine administration. These results indicate that TRPV1 and NMDA receptors in the spinal cord are associated with inflammatory pain transmission, and inhibition of TRPV1 may reduce inflammatory pain via NMDA receptors.

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