Methylene blue induces an analgesic effect by significantly decreasing neural firing rates and improves pain behaviors in rats

Lee, Seung Won; Moon, Sangook; Park, Jin-Sung; Suh, Hye Rim; Han, Hee Chul

doi:10.1016/j.bbrc.2021.01.008

Cited by 4 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ultimately, MB improved pain behaviors in rodents. These results demonstrate that MB abates pain by markedly suppressing neural excitability (Lee et al, 2021).…”

Section: Mb and Sodium Current Reduction Early Studies For Mb And I Namentioning

confidence: 60%

“…Ultimately, these anti-inflammatory responses contribute to restoring inflamed tissues and lessening pain (Table 1; Vutskits et al, 2008;Dinc et al, 2015;Ahn et al, 2017;Li et al, 2018;Zheng and Li, 2019). In addition, MB reduces the amplitude of I NA , accelerates the I NA inactivation, delays the shift from inactivation to recovery state in neurons, and importantly decreases neural firing rates, which can therefore alleviate pain by impeding VGSC-mediated neuronal excitability (Zhang et al, 2010;Lee et al, 2021). Lastly, MB is involved in denervation.…”

Section: Discussionmentioning

confidence: 99%

“…In general, voltage-gated sodium channels (VGSCs) play an important role in evoking action potentials (APs) and, when activated, they consequently contribute to exciting neurons and thus facilitating communication with other ones. Interestingly, MB decreased significantly I NA (voltage-gated sodium currents) in hippocampal CA1 neurons and, more importantly, attenuated markedly neural firing rates in the afferent nerve fibers (Zhang et al, 2010;Lee et al, 2021), which implies that MB may impede pain transmission by dampening neuronal excitability elicited by VGSCs.…”

Section: Introductionmentioning

confidence: 94%

“…Importantly, Lee et al (2021) performed the first in vivo experiments to investigate the link between MB-mediated neural firing patterns and pain reduction in rats using in vivo single nerve recordings and behavioral studies. This study showed dramatic results that neural firing rates significantly decreased in a dose-dependent manner after MB administration and, notably, this event lasted longer than that of lidocaine, showing anestheticlike firing patterns.…”

Section: Mb and Sodium Current Reduction Early Studies For Mb And I Namentioning

confidence: 99%

“…Accordingly, it is natural to postulate that VGSCs and AP generation play a crucial role even in pain transmission (Dubin and Patapoutian, 2010;Bennett et al, 2019). Interestingly, multiple evidence demonstrates that MB silences excitable cells (or nerves) by significantly attenuating I NA and AP production, which ultimately leads to pain relief (Armstrong and Croop, 1982;Starkus et al, 1984Starkus et al, , 1993Zhang et al, 2010;Lee et al, 2021). Therefore, these two crucial electrophysiological activities, weakened sodium currents and decreased neural firing rates, are possible causes that can elucidate how MB contributes to pain relief.…”

Section: Silenced Excitable Neurons As a Critical Cause Of Pain Reliefmentioning

confidence: 99%

See 4 more Smart Citations

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

Lee

Han

2021

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

Methylene blue (MB) is a cationic thiazine dye, widely used as a biological stain and chemical indicator. Growing evidence have revealed that MB functions to restore abnormal vasodilation and notably it is implicated even in pain relief. Physicians began to inject MB into degenerated disks to relieve pain in patients with chronic discogenic low back pain (CDLBP), and some of them achieved remarkable outcomes. For osteoarthritis and colitis, MB abates inflammation by suppressing nitric oxide production, and ultimately relieves pain. However, despite this clinical efficacy, MB has not attracted much public attention in terms of pain relief. Accordingly, this review focuses on how MB lessens pain, noting three major actions of this dye: anti-inflammation, sodium current reduction, and denervation. Moreover, we showed controversies over the efficacy of MB on CDLBP and raised also toxicity issues to look into the limitation of MB application. This analysis is the first attempt to illustrate its analgesic effects, which may offer a novel insight into MB as a pain-relief dye.

show abstract

“…Ultimately, MB improved pain behaviors in rodents. These results demonstrate that MB abates pain by markedly suppressing neural excitability (Lee et al, 2021).…”

Section: Mb and Sodium Current Reduction Early Studies For Mb And I Namentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Mb and Sodium Current Reduction Early Studies For Mb And I Namentioning

confidence: 99%

Section: Silenced Excitable Neurons As a Critical Cause Of Pain Reliefmentioning

confidence: 99%

See 3 more Smart Citations

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

Lee

Han

2021

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

Application of methylene blue combined with ropivacaine intercostal nerve block in postoperative analgesia of autologous costal cartilage augmentation rhinoplasty

2022

View full text Add to dashboard Cite

Objective To observe the effect of methylene blue combined with ropivacaine intercostal nerve block on postoperative analgesia after autologous costal cartilage augmentation rhinoplasty. Methods In this study 100 female patients who underwent autologous costal cartilage comprehensive augmentation rhinoplasty in Chongqing Huamei Plastic Surgery Hospital from April to November 2021 were randomly divided into an experimental group and a control group, with 50 cases in each group. In the experimental group methylene blue was combined with ropivacaine intercostal nerve block as patient controlled intravenous analgesia (PCIA), and the control group was ropivacaine intercostal nerve block combined with PCIA. The visual analogue scale (VAS) scores of resting and coughing at 6 h (T1), 24 h (T2), 48 h (T3), 72 h (T4) after surgery were recorded and evaluated. At the same time, the number and times of oral analgesics were recorded as well as nausea, vomiting, burning pain and paresthesia. Results The VAS scores of the experimental group were lower than those of the control group at all time points. At 6 h, 24 h and 48 h after surgery, the VAS score of the experimental group was lower than that in the control group, but the difference was not statistically significant (P > 0.05). The VAS score of calm 72 h after surgery in the experimental group was significantly lower than that in the control group (P < 0.05). The analgesic effect of the two groups was better when they coughed after surgery. At 6 h after surgery, the VAS score of coughing in the experimental group was lower than that in the control group, but the difference was not statistically significant (P > 0.05); At 24 h, 48 h and 72 h after surgery, the VAS score of the coughing state in the experimental group was significantly lower than that in the control group (P < 0.05). Conclusion Intercostal nerve block with methylene blue combined with ropivacaine can achieve good postoperative analgesic effects in augmentation rhinoplasty with autologous costal cartilage

show abstract

Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model

Banik,

Sia,

Johns

et al. 2024

Mol Pain

View full text Add to dashboard Cite

Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1β and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1β, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.

show abstract

Methylene blue induces an analgesic effect by significantly decreasing neural firing rates and improves pain behaviors in rats

Cited by 4 publications

References 29 publications

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

Application of methylene blue combined with ropivacaine intercostal nerve block in postoperative analgesia of autologous costal cartilage augmentation rhinoplasty

Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model

Contact Info

Product

Resources

About