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

Seung Won Lee, Hee Chul Han, Seung Won Lee, Hee Chul Han

Abstract

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.

Keywords: anti-inflammation; denervation; methylene blue; pain; sodium current.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Lee and Han.

Figures

FIGURE 1
FIGURE 1
MB is involved in anti-inflammation by suppressing iNOS/NO-NF-κB pathway. (A) Basically, MB downregulates both eNOS and sGC that are major factors converting GTP to cGMP, ultimately leading to vasoconstriction. (B) Upon tissue injury, iNOS functions as a strong inflammatory mediator in different types of cells. It inhibits Sirt1 activation by NO-mediated S-nitrosylation, which in turn activates NF-κB and p53 to facilitate inflammatory cytokine expression and apoptosis, respectively. Of note, NF-κB activation intensifies these events by activating iNOS/NO-NF-κB pathway. Conversely, MB directly abates iNOS expression and moreover decreases the binding of NF-κB to iNOS promoter, which consequently interrupts this inflammatory signaling. (C) Meanwhile, NMDA receptors are activated during nerve injury and induces Ca2+ influx, which then results in the excessive expression of nNOS and markedly activates nNOS/NO signaling. The increased NO production stimulates NMDA receptors and triggers NO/cGMP/PKG cascade, which promotes the subsequent BNDF upregulation and neurotransmitter release and ultimately induces long-term hyperexcitability and central sensitization. Notably, BDNF and peroxynitrite potentiate NMDA receptors, which stimulate nNOS expression again. However, MB weakens these responses by inhibiting nNOS and sGC activation, thus may prevent the development of persistent pain.LTH, long-term hyperexcitability; STZ, sensitization; NT, neurotransmitter; CP, chronic pain.
FIGURE 2
FIGURE 2
MB significantly attenuates sodium currents by blocking VGSCs. (A) In general, VGSCs allow sodium ions to flow into the cell in the activated state. (B) However, early researchers found that the gate and sodium currents of the channels were markedly suppressed post-MB treatment. And notably, this event was maintained even after pronase treatment. Thus, they interpreted this event as MB functions as a pore blocker rather than an inactivation enhancer.
FIGURE 3
FIGURE 3
MB contributes to pain reduction via three major routes. (A) First of all, MB is deeply involved in anti-inflammation. MB application blocks iNOS/NO signaling by downregulating iNOS, and suppresses P2 × 3R and lncRNA expression, NF-κB activation, and inflammasome formation, which thereby decreases inflammatory cytokine levels. These events are ultimately followed by pain reduction with the prevention of tissue degradation and swelling. (B) In addition, MB application attenuates neuronal excitability by decreasing INA and firing rates. These altered electrophysiological properties may contribute to pain relief by blocking synaptic transmission. (C) Lastly, MB application improved chronic PA and LBP. An electron microscopic experiment demonstrated that such efficacy was due to the death of nerve endings.

References

    1. Ahn H., Kang S. G., Yoon S. I., Ko H. J., Kim P. H., Hong E. J., et al. (2017). Methylene blue inhibits NLRP3, NLRC4, AIM2, and non-canonical inflammasome activation. Sci. Rep. 7:12409.
    1. Al-Najjim M., Shah R., Rahuma M., Gabbar O. A. (2018). Lumbar facet joint injection in treating low back pain: radiofrequency denervation versus SHAM procedure. Systematic review. J. Orthop. 15 1–8. 10.1016/j.jor.2017.10.001
    1. Armstrong C. M., Croop R. S. (1982). Simulation of Na channel inactivation by thiazine dyes. J Gen Physiol 80 641–662. 10.1085/jgp.80.5.641
    1. Aubrey B. J., Kelly G. L., Janic A., Herold M. J., Strasser A. (2018). How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 25 104–113. 10.1038/cdd.2017.169
    1. Bach K. K., Lindsay F. W., Berg L. S., Howard R. S. (2004). Prolonged postoperative disorientation after methylene blue infusion during parathyroidectomy. Anesth Analg 99 1573–1574. 10.1213/
    1. Bennett D. L., Clark A. J., Huang J., Waxman S. G., Dib-Hajj S. D. (2019). The role of voltage-gated sodium channels in pain signaling. Physiol. Rev, 99 1079–1151. 10.1152/physrev.00052.2017
    1. Bernier L. P., Ase A. R., Seguela P. (2018). P2X receptor channels in chronic pain pathways. Br. J. Pharmacol. 175 2219–2230. 10.1111/bph.13957
    1. Bogduk N. (2010). A cure for back pain? Pain 149 7–8. 10.1016/j.pain.2009.05.022
    1. Bouillaud J. (1836). Essai sur la Philosophie Médicale et sur les Généralités de la Clinique Médicale. Oxford: Université d’Oxford. De Just Rouvier et E. Le Bouvier.
    1. Boyer E. W., Shannon M. (2005). The serotonin syndrome. N. Engl. J. Med. 352 1112–1120.
    1. Cabanis P. J. G. (1803). Du Degré de Certitude de la Médecine. Paris: Crapelet.
    1. Chen J., Ao L., Yang J. (2019). Long non-coding RNAs in diseases related to inflammation and immunity. Ann. Transl. Med. 7:494. 10.21037/atm.2019.08.37
    1. Chen W., Walwyn W., Ennes H. S., Kim H., Mcroberts J. A., Marvizón J. C. (2014). BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals. Eur. J. Neurosci. 39 1439–1454. 10.1111/ejn.12516
    1. Chu Y.-C., Guan Y., Skinner J., Raja S. N., Johns R. A., Tao Y.-X. (2005). Effect of genetic knockout or pharmacologic inhibition of neuronal nitric oxide synthase on complete Freund’s adjuvant-induced persistent pain. Pain 119 113–123. 10.1016/j.pain.2005.09.024
    1. Cohen N., Robinson D., Ben-Ezzer J., Hemo Y., Hasharoni A., Wolmann Y., et al. (2000). Reduced NO accumulation in arthrotic cartilage by exposure to methylene blue. Acta Orthop. Scand. 71 630–636. 10.1080/000164700317362299
    1. Demir I. E., Heinrich T., Carty D. G., Saricaoglu ØC., Klauss S., Teller S., et al. (2019). Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis. EBioMedicine 46 431–443. 10.1016/j.ebiom.2019.07.055
    1. Deng M., Huang H., Ma Y. G., Zhou Y., Chen Q., Xie P. (2021). Intradiskal injection of methylene blue for discogenic back pain: a meta-analysis of randomized controlled trials. J. Neurol. Surg. A Cent Eur. Neurosurg. 82 161–165. 10.1055/s-0040-1721015
    1. Deng S., Yu K., Zhang B., Yao Y., Wang Z., Zhang J., et al. (2015). Toll-like receptor 4 promotes NO synthesis by upregulating GCHI expression under oxidative stress conditions in sheep Monocytes/Macrophages. Oxid. Med. Cell.Longev. 2015:359315.
    1. Dinc S., Caydere M., Akgul G., Yenidogan E., Hucumenoglu S., Rajesh M. (2015). Methylene Blue inhibits the inflammatory process of the acetic acid-induced colitis in the rat colonic mucosa. Int. Surg. 100 1364–1374. 10.9738/intsurg-d-15-00118.1
    1. Dubin A. E., Patapoutian A. (2010). Nociceptors: the sensors of the pain pathway. J. Clin. Invest. 120 3760–3772. 10.1172/jci42843
    1. Etter L., Myers S. A. (2002). Pruritus in systemic disease: mechanisms and management. Dermatol. Clin. 20 459–472. 10.1016/s0733-8635(02)00011-6
    1. Eusebio E. B., Graham J., Mody N. (1990). Treatment of intractable pruritus ani. Dis Colon Rectum. 33 770–772. 10.1007/bf02052324
    1. Floris G., Cadeddu R., Bortolato M. (2020). “The effects of serotonin degradation on psychopathology: role of monoamine oxidase,” in Handbook of the Behavioral Neurobiology of Serotonin, eds Müller C. P., Cunningham K. A. (Cambridge, MA: Academic Press; ), 267–278. 10.1016/b978-0-444-64125-0.00014-1
    1. Funakoshi A., Tatsuno K., Shimauchi T., Fujiyama T., Ito T., Tokura Y. (2019). Cholecystokinin downregulates psoriatic inflammation by its possible self-regulatory effect on epidermal keratinocytes. J. Immunol. 202:2609. 10.4049/jimmunol.1801426
    1. Gillman P. K. (2011). CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity. J. Psychopharmacol. 25 429–436. 10.1177/0269881109359098
    1. Gupta G., Radhakrishna M., Chankowsky J., Asenjo J. F. (2012). Methylene blue in the treatment of discogenic low back pain. Pain Physician 15 333–338. 10.36076/ppj.2012/15/333
    1. Harth M., Nielson W. R. (2019). Pain and affective distress in arthritis: relationship to immunity and inflammation. Expert Rev. Clin. Immunol. 15 541–552. 10.1080/1744666x.2019.1573675
    1. Huang C., Tong L., Lu X., Wang J., Yao W., Jiang B., et al. (2015). Methylene blue attenuates iNOS induction through suppression of transcriptional factor binding amid iNOS mRNA transcription. J. Cell Biochem. 116 1730–1740. 10.1002/jcb.25132
    1. Jiang M., Wang H., Liu Z., Lin L., Wang L., Xie M., et al. (2020). Endoplasmic reticulum stress-dependent activation of iNOS/NO-NF-κB signaling and NLRP3 inflammasome contributes to endothelial inflammation and apoptosis associated with microgravity. FASEB J. 34 10835–10849. 10.1096/fj.202000734r
    1. Kallewaard J. W., Wintraecken V. M., Geurts J. W., Willems P. C., Van Santbrink H., Terwiel C. T. M., et al. (2019). A multicenter randomized controlled trial on the efficacy of intradiscal methylene blue injection for chronic discogenic low back pain: the IMBI study. Pain 160 945–953. 10.1097/j.pain.0000000000001475
    1. Kanneganti T. D. (2015). The inflammasome: firing up innate immunity. Immunol. Rev. 265 1–5. 10.1111/imr.12297
    1. Kapadia K., Cheung F., Lee W., Thalappillil R., Florence F. B., Kim J. (2016). Methylene blue causing serotonin syndrome following cystocele repair. Urol. Case Rep. 9 15–17. 10.1016/j.eucr.2016.07.012
    1. Kaski S. W., White A. N., Gross J. D., Siderovski D. P. (2021). Potential for kappa-opioid receptor agonists to engineer nonaddictive analgesics: a narrative review. Anesth. Anal. 132 406–419. 10.1213/ane.0000000000005309
    1. Keppel Hesselink J. M. (2020). Rediscovery of ceruletide, a CCK agonist, as an analgesic drug. J. Pain Res. 13 123–130. 10.2147/jpr.s232714
    1. Khan M. A., North A. P., Chadwick D. R. (2007). Prolonged postoperative altered mental status after methylene blue infusion during parathyroidectomy: a case report and review of the literature. Ann. R. Coll. Surg. Engl. 89 W9–W11.
    1. Kim J. H., Kim D. H., Lee Y. P. (2019). Long-term follow-up of intradermal injection of methylene blue for intractable, idiopathic pruritus ani. Tech. Coloproctol. 23 143–149. 10.1007/s10151-019-01934-x
    1. Kim K. H., Kim J. I., Han J. A., Choe M. A., Ahn J. H. (2011). Upregulation of neuronal nitric oxide synthase in the periphery promotes pain hypersensitivity after peripheral nerve injury. Neuroscience 190 367–378. 10.1016/j.neuroscience.2011.05.064
    1. Kim S. H., Ahn S. H., Cho Y. W., Lee D. G. (2012). Effect of intradiscal methylene blue injection for the chronic discogenic low back pain: one year prospective follow-up study. Ann. Rehabil. Med. 36 657–664. 10.5535/arm.2012.36.5.657
    1. Kõks S., Fernandes C., Kurrikoff K., Vasar E., Schalkwyk L. C. (2008). Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor deficient mice. Behav. Brain Res. 188 62–70. 10.1016/j.bbr.2007.10.020
    1. Kourosh-Arami M., Hosseini N., Mohsenzadegan M., Komaki A., Joghataei M. T. (2020). Neurophysiologic implications of neuronal nitric oxide synthase. Rev. Neurosci. 31 617–636. 10.1515/revneuro-2019-0111
    1. Kruger L. C., Isom L. L. (2016). Voltage-Gated Na+ Channels: not just for conduction. Cold Spring Harbor Perspect. Biol. 8:a029264. 10.1101/cshperspect.a029264
    1. Lacagnina M. J., Watkins L. R., Grace P. M. (2018). Toll-like receptors and their role in persistent pain. Pharmacol. Ther. 184 145–158. 10.1016/j.pharmthera.2017.10.006
    1. Leclaire R., Fortin L., Lambert R., Bergeron Y. M., Rossignol M. (2001). Radiofrequency facet joint denervation in the treatment of low back pain: a placebo-controlled clinical trial to assess efficacy. Spine 26 1411–1416. discussion 1417, 10.1097/00007632-200107010-00003
    1. Lee S. W., Moon S. W., Park J. S., Suh H. R., Han H. C. (2021). Methylene blue induces an analgesic effect by significantly decreasing neural firing rates and improves pain behaviors in rats. Biochem. Biophys. Res. Commun. 541 36–42. 10.1016/j.bbrc.2021.01.008
    1. Leiper J., Nandi M. (2011). The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis. Nat. Rev. Drug Discov. 10 277–291. 10.1038/nrd3358
    1. Levi D. S., Horn S., Walko E. (2014). Intradiskal methylene blue treatment for diskogenic low back pain. PM R 6 1030–1037. 10.1016/j.pmrj.2014.04.008
    1. Levine R., Richeimer S. H. (2011). Spinal methylene blue is hazardous. PAIN 152 952–953. 10.1016/j.pain.2011.01.009
    1. Lewin M. R., Walters E. T. (1999). Cyclic GMP pathway is critical for inducing long–term sensitization of nociceptive sensory neurons. Nat. Neurosci. 2 18–23. 10.1038/4520
    1. Li G., Jiang H., Zheng C., Zhu G., Xu Y., Sheng X., et al. (2017). Long noncoding RNA MRAK009713 is a novel regulator of neuropathic pain in rats. PAIN 158 2042–2052. 10.1097/j.pain.0000000000001013
    1. Li H., Liu S., Wang Z., Zhang Y., Wang K. (2020). Hydrogen sulfide attenuates diabetic neuropathic pain through NO/cGMP/PKG pathway and μ-opioid receptor. Exp. Biol. Med. 245 823–834. 10.1177/1535370220918193
    1. Li X., Tang C., Wang J., Guo P., Wang C., Wang Y., et al. (2018). Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3. Exp. Ther. Med. 15 3856–3864.
    1. Lin Z. H., Wang S. Y., Chen L. L., Zhuang J. Y., Ke Q. F., Xiao D. R., et al. (2017). Methylene blue mitigates acute neuroinflammation after spinal cord injury through inhibiting nlrp3 inflammasome activation in microglia. Front. Cell Neurosci. 11:391. 10.3389/fncel.2017.00391
    1. Lundberg J. O., Weitzberg E., Gladwin M. T. (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat. Rev. Drug Discov. 7 156–167. 10.1038/nrd2466
    1. Luo Z. D., Cizkova D. (2000). The role of nitric oxide in nociception. Curr. Rev. Pain 4 459–466. 10.1007/s11916-000-0070-y
    1. Maas E. T., Ostelo R. W., Niemisto L., Jousimaa J., Hurri H., Malmivaara A., et al. (2015). Radiofrequency denervation for chronic low back pain. Cochrane Database Syst. Rev. CD008572.
    1. Machelska H., Labuz D., Przewłocki R., Przewłocka B. (1997). Inhibition of nitric oxide synthase enhances antinociception mediated by mu, delta and kappa opioid receptors in acute and prolonged pain in the rat spinal cord. J. Pharmacol. Exp. Ther. 282 977–984.
    1. Majithia A., Stearns M. P. (2006). Methylene blue toxicity following infusion to localize parathyroid adenoma. J. Laryngol. Otol. 120 138–140. 10.1017/s0022215105005098
    1. Martindale S. J., Stedeford J. C. (2003). Neurological sequelae following methylene blue injection for parathyroidectomy. Anaesthesia 58 1041–1042. 10.1046/j.1365-2044.2003.03415_23.x
    1. Mathew S., Linhartova L., Raghuraman G. (2006). Hyperpyrexia and prolonged postoperative disorientation following methylene blue infusion during parathyroidectomy. Anaesthesia 61 580–583. 10.1111/j.1365-2044.2006.04619.x
    1. Matsuda M., Huh Y., Ji R. R. (2019). Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain. J. Anesth. 33 131–139. 10.1007/s00540-018-2579-4
    1. MHRA, (2009). Methylthioninium Chloride (methylene blue): Update on Central Nervous System (CNS) Toxicity. London: Medicines and Healthcare products Regulatory Agency, 2.
    1. Miclescu A. A., Svahn M., Gordh T. E. (2015). Evaluation of the protein biomarkers and the analgesic response to systemic methylene blue in patients with refractory neuropathic pain: a double-blind, controlled study. J. Pain Res. 8 387–397. 10.2147/jpr.s84685
    1. Mihai R., Mitchell E. W., Warwick J. (2007). Dose-response and postoperative confusion following methylene blue infusion during parathyroidectomy. Can. J. Anaesth. 54 79–81. 10.1007/bf03021907
    1. Mukherjee P., Cinelli M. A., Kang S., Silverman R. B. (2014). Development of nitric oxide synthase inhibitors for neurodegeneration and neuropathic pain. Chem. Soc. Rev. 43 6814–6838. 10.1039/c3cs60467e
    1. Nakazawa H., Chang K., Shinozaki S., Yasukawa T., Ishimaru K., Yasuhara S., et al. (2017). iNOS as a driver of inflammation and apoptosis in mouse skeletal muscle after burn injury: possible involvement of sirt1 s-nitrosylation-mediated acetylation of p65 NF-κB and p53. PLoS One 12:e0170391. 10.1371/journal.pone.0170391
    1. Nath S., Nath C. A., Pettersson K. (2008). Percutaneous lumbar zygapophysial (Facet) joint neurotomy using radiofrequency current, in the management of chronic low back pain: a randomized double-blind trial. Spine 33 1291–1297. 10.1097/brs.0b013e31817329f0
    1. Ng B. K. W., Cameron A. J. D. (2010). The role of methylene blue in serotonin syndrome: a systematic review. Psychosomatics 51 194–200. 10.1016/s0033-3182(10)70685-x
    1. Ng B. K. W., Cameron A. J. D., Liang R., Rahman H. (2008). Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review. Can. J. Anesth. 55 36–41. 10.1007/bf03017595
    1. North R. A. (2004). P2X3 receptors and peripheral pain mechanisms. J. Physiol. 554 301–308.
    1. Osmanlıoğlu H. Ø, Yıldırım M. K., Akyuva Y., Yıldızhan K., Nazıroğlu M. (2020). Morphine induces apoptosis, inflammation, and mitochondrial oxidative stress via activation of TRPM2 Channel and nitric oxide signaling pathways in the hippocampus. Mol. Neurobiol. 57 3376–3389. 10.1007/s12035-020-01975-6
    1. Pall M. L. (2002). NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity. Faseb J. 16 1407–1417. 10.1096/fj.01-0861hyp
    1. Pan P. F., Wang Y., Li X. P., Yang C. B., Zhong H., Du X. X., et al. (2019). Effects of methylene blue on the nitric oxide-soluble guanylate cyclase-cyclic guanylyl monophosphate pathway and cytokine levels in rats with sepsis. Int. J. Clin. Exp. Med. 12 12203–12211.
    1. Peng B., Pang X., Wu Y., Zhao C., Song X. (2010). A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back pain. Pain 149 124–129. 10.1016/j.pain.2010.01.021
    1. Peng B., Zhang Y., Hou S., Wu W., Fu X. (2007). Intradiscal methylene blue injection for the treatment of chronic discogenic low back pain. Eur. Spine J. 16 33–38. 10.1007/s00586-006-0076-1
    1. Peter C., Hongwan D., Küpfer A., Lauterburg B. H. (2000). Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur. J. Clin. Pharmacol. 56 247–250. 10.1007/s002280000124
    1. Pollack G., Pollack A., Delfiner J., Fernandez J. (2009). Parathyroid surgery and methylene blue: a review with guidelines for safe intraoperative use. Laryngosc. 119 1941–1946. 10.1002/lary.20581
    1. Polydefkis M., Hauer P., Sheth S., Sirdofsky M., Griffin J. W., Mcarthur J. C. (2004). The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain 127 1606–1615. 10.1093/brain/awh175
    1. Quirion B., Bergeron F., Blais V., Gendron L. (2020). The delta-opioid receptor; a target for the treatment of pain. Front. Mol. Neurosci. 13:52. 10.3389/fnmol.2020.00052
    1. Rathinam V. A., Fitzgerald K. A. (2016). Inflammasome complexes: emerging mechanisms and effector functions. Cell 165 792–800. 10.1016/j.cell.2016.03.046
    1. Rey-Funes M., Larrayoz I. M., Fernández J. C., Contartese D. S., Rolón F., Inserra P. I. F., et al. (2016). Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy. Am. J. Physiol. Regul. Integr. Comp. Physiol. 310 R1011–R1019.
    1. Roca-Lapirot O., Fossat P., Ma S., Egron K., Trigilio G., López-González M. J., et al. (2019). Acquisition of analgesic properties by the cholecystokinin (CCK)/CCK2 receptor system within the amygdala in a persistent inflammatory pain condition. Pain 160 345–357. 10.1097/j.pain.0000000000001408
    1. Rocha P. A., Ferreira A. F. B., Da Silva J. T., Alves A. S., Martins D. O., Britto L. R. G., et al. (2020). Effects of selective inhibition of nNOS and iNOS on neuropathic pain in rats. Mol. Cell. Neurosci. 105:103497. 10.1016/j.mcn.2020.103497
    1. Roldan C. J., Nouri K., Chai T., Huh B. (2017). Methylene blue for the treatment of intractable pain associated with oral mucositis. Pain Pract. 17 1115–1121. 10.1111/papr.12566
    1. Rowley M., Riutort K., Shapiro D., Casler J., Festic E., Freeman W. D. (2009). Methylene blue-associated serotonin syndrome: a ‘Green’ encephalopathy after parathyroidectomy. Neurocrit. Care 11 88–93. 10.1007/s12028-009-9206-z
    1. Rygick A. N. (1968). Atlas of the Operations on the Rectum and Colon. Moscow: Meduch Posovie.
    1. Saia R. S., Ribeiro A. B., Giusti H. (2020). Cholecystokinin modulates the mucosal inflammatory response and prevents the lipopolysaccharide-induced intestinal epithelial barrier dysfunction. Shock 53 242–251. 10.1097/shk.0000000000001355
    1. Schiltenwolf M., Fischer C., Kunz P. (2011). How perfect studies may be? Comment on Peng et al. A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back pain. Pain 2010;149:124-9. Pain 152:954. author reply 954-955, 10.1016/j.pain.2011.01.008
    1. Schirmer R. H., Coulibaly B., Stich A., Scheiwein M., Merkle H., Eubel J., et al. (2003). Methylene blue as an antimalarial agent. Redox Rep. 8 272–275. 10.1179/135100003225002899
    1. Schirmer R. H., Adler H., Pickhardt M., Mandelkow E. (2011). Lest we forget you–methylene blue. Neurobiol. Aging 32:2325.e7–16. 10.1016/j.neurobiolaging.2010.12.012
    1. Schmid R., Evans R. J. (2019). ATP-Gated P2X receptor channels: molecular insights into functional roles. Annu. Rev. Physiol. 81 43–62. 10.1146/annurev-physiol-020518-114259
    1. Schwiebert C., Irving C., Gillman P. K. (2009). Small doses of methylene blue, previously considered safe, can precipitate serotonin toxicity. Anaesthesia 64 924–924. 10.1111/j.1365-2044.2009.06029.x
    1. Shanmugam G., Kent B., Alsaiwadi T., Baskett R. (2008). Serotonin syndrome following cardiac surgery. Interact. Cardiovasc. Thorac. Surg. 7 656–657. 10.1510/icvts.2007.173104
    1. Starkus J. G., Heggeness S. T., Rayner M. D. (1984). Kinetic analysis of sodium channel block by internal methylene blue in pronased crayfish giant axons. Biophys. J. 46 205–218. 10.1016/s0006-3495(84)84014-x
    1. Starkus J. G., Rayner M. D., Fleig A., Ruben P. C. (1993). Fast and slow inactivation of sodium channels: effects of photodynamic modification by methylene blue. Biophys. J. 65 715–726. 10.1016/s0006-3495(93)81098-1
    1. Stephan G., Huang L., Tang Y., Vilotti S., Fabbretti E., Yu Y., et al. (2018). The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel. Nat. Commun. 9:1354.
    1. Sun J., Chen S.-R., Pan H.-L. (2020). μ-Opioid receptors in primary sensory neurons are involved in supraspinal opioid analgesia. Brain Res. 1729:146623. 10.1016/j.brainres.2019.146623
    1. Sung Y.-J., Sofoluke N., Nkamany M., Deng S., Xie Y., Greenwood J., et al. (2017). A novel inhibitor of active protein kinase G attenuates chronic inflammatory and osteoarthritic pain. Pain 158 822–832. 10.1097/j.pain.0000000000000832
    1. Surprenant A., North R. A. (2009). Signaling at purinergic P2X receptors. Annu. Rev. Physiol. 71 333–359. 10.1146/annurev.physiol.70.113006.100630
    1. Swanson K. V., Deng M., Ting J. P. (2019). The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19 477–489. 10.1038/s41577-019-0165-0
    1. Tanga F. Y., Nutile-Mcmenemy N., Deleo J. A. (2005). The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc. Natl. Acad. Sci. U.S.A. 102 5856–5861. 10.1073/pnas.0501634102
    1. Top W. M., Gillman P. K., De Langen C. J., Kooy A. (2014). Fatal methylene blue associated serotonin toxicity. Neth. J. Med. 72 179–181.
    1. Torres-López J. E., Juárez-Rojop I. E., Granados-Soto V., Diaz-Zagoya J. C., Flores-Murrieta F. J., Ortíz-López J. U., et al. (2007). Peripheral participation of cholecystokinin in the morphine-induced peripheral antinociceptive effect in non-diabetic and diabetic rats. Neuropharmacology 52 788–795. 10.1016/j.neuropharm.2006.09.015
    1. Vutskits L., Briner A., Klauser P., Gascon E., Dayer A. G., Kiss J. Z., et al. (2008). Adverse effects of methylene blue on the central nervous system. Anesthesiology 108 684–692. 10.1097/aln.0b013e3181684be4
    1. Wainwright M., Crossley K. B. (2002). Methylene Blue–a therapeutic dye for all seasons? J. Chemother. 14 431–443. 10.1179/joc.2002.14.5.431
    1. Wang F., Ma S.-B., Tian Z.-C., Cui Y.-T., Cong X.-Y., Wu W.-B., et al. (2021). Nociceptor-localized cGMP-dependent protein kinase I is a critical generator for central sensitization and neuropathic pain. PAIN 162 135–151. 10.1097/j.pain.0000000000002013
    1. Wang J., Ou S.-W., Wang Y.-J. (2017). Distribution and function of voltage-gated sodium channels in the nervous system. Channels 11 534–554. 10.1080/19336950.2017.1380758
    1. Wang R., Ma C., Han Y., Tan M., Lu L. (2019). Effectiveness of denervation therapy on pain and joint function for patients with refractory knee osteoarthritis: a systematic review and meta-analysis. Pain Physician 22 341–352. 10.36076/ppj/2019.22.341
    1. Wang X., Zhang S., Xie Z., Chen L., Yang B., Wu X. (2019). deleterious effects of methylene blue on rat nucleus pulposus cell in vitro: changes in cell viability and secretory phenotype in exposed cells. J. Neurol. Surg. A Cent. Eur. Neurosurg. 80 174–179. 10.1055/s-0038-1670638
    1. Wolin M. S., Cherry P. D., Rodenburg J. M., Messina E. J., Kaley G. (1990). Methylene blue inhibits vasodilation of skeletal muscle arterioles to acetylcholine and nitric oxide via the extracellular generation of superoxide anion. J. Pharmacol. Exp. Ther. 254 872–876.
    1. Wolvetang T., Janse R., Ter Horst M. (2016). Serotonin syndrome after methylene blue administration during cardiac surgery: a case report and review. J. Cardiothorac. Vasc. Anesth. 30 1042–1045. 10.1053/j.jvca.2015.11.019
    1. Yadav S., Surolia A. (2019). Lysozyme elicits pain during nerve injury by neuronal Toll-like receptor 4 activation and has therapeutic potential in neuropathic pain. Sci. Transl. Med. 11:eaav4176. 10.1126/scitranslmed.aav4176
    1. Yang Y., Li Q., He Q.-H., Han J.-S., Su L., Wan Y. (2018). Heteromerization of μ-opioid receptor and cholecystokinin B receptor through the third transmembrane domain of the μ-opioid receptor contributes to the anti-opioid effects of cholecystokinin octapeptide. Exp. Mol. Med. 50 1–16. 10.1038/s12276-018-0090-5
    1. Yang Y., Wang H., Kouadir M., Song H., Shi F. (2019). Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 10:128.
    1. Ye Y., Wang Y., Yang Y., Tao L. (2020). Aloperine suppresses LPS-induced macrophage activation through inhibiting the TLR4/NF-κB pathway. Inflammation Res. 69 375–383. 10.1007/s00011-019-01313-0
    1. Yeung A. W. K., Georgieva M. G., Atanasov A. G., Tzvetkov N. T. (2019). Monoamine oxidases (MAOs) as privileged molecular targets in neuroscience: research literature analysis. Front. Mol. Neurosci. 12:143. 10.3389/fnmol.2019.00143
    1. Zhang H., Li F., Li W. W., Stary C., Clark J. D., Xu S., et al. (2016). The inflammasome as a target for pain therapy. Br. J. Anaesth. 117 693–707. 10.1093/bja/aew376
    1. Zhang X., Hao J., Hu Z., Yang H. (2016). Clinical evaluation and magnetic resonance imaging assessment of intradiscal methylene blue injection for the treatment of discogenic low back pain. Pain Physician 19 E1189–E1195.
    1. Zhang L., Liu Y., Huang Z., Nan L., Wang F., Zhou S., et al. (2019). Toxicity effects of methylene blue on rat intervertebral disc annulus fibrosus cells. Pain Physician 22 155–164. 10.36076/ppj/2019.22.155
    1. Zhang Y., Zhao J., Zhang T., Yang Z. (2010). In vitro assessment of the effect of methylene blue on voltage-gated sodium channels and action potentials in rat hippocampal CA1 pyramidal neurons. Neurotoxicology 31 724–729. 10.1016/j.neuro.2010.07.001
    1. Zhao X., Tang Z., Zhang H., Atianjoh F. E., Zhao J.-Y., Liang L., et al. (2013). A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons. Nat. Neurosci. 16 1024–1031. 10.1038/nn.3438
    1. Zheng J., Li Q. (2019). Methylene blue regulates inflammatory response in osteoarthritis by noncoding long chain RNA CILinc02. J. Cell Biochem. 120 3331–3338. 10.1002/jcb.27602
    1. Zuschlag Z. D., Warren M. W., Schultz S. K. (2018). Serotonin toxicity and urinary analgesics: a case report and systematic literature review of methylene blue-induced serotonin syndrome. Psychosomatics 59 539–546. 10.1016/j.psym.2018.06.012

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