A review on hydrogen sulfide: Is it pro-nociceptive or anti-nociceptive?

Year 2022, Volume: 52 Issue: 1, 101 - 107, 28.04.2022

Hazal Eken , Nurcan Bektaş Türkmen , Rana Arslan

https://doi.org/10.26650/IstanbulJPharm.2022.913936

Abstract

Pain is sensed by the activation of painful nociceptors in the periphery or by pain mediators, such as bradykinin, serotonin, histamine, and prostaglandin, released from the damaged tissue, afferent transmission to the medulla spinalis, and by trans- mission stages to the high centers over the dorsal horn. Pain, which was seen as only a warning sign in the past, is now ac- cepted as a phenomenon in itself that needs to be treated and the search for new, stronger active substances with fewer side effects in the treatment of pain is in demand. Hydrogen sulfide (H2S) is a modulator of T-type Ca+2 channels, especially in Cav3.2, which are known to play a critical role in the processing of pain. H2S can also show an anti-nociceptive effect by open- ing K+ channels and blocking nociceptors. Exciting preclinical data has demonstrated that H2S-derived Non-steroidal anti- inflammatory drugs (NSAIDs) and analgesic agents can be used to treat various types of pain. H2S increases the resistance of gastric mucosa against injury occurred by drugs used for pain relief and accelerates its repair, so it provides an advantage to derivatized drugs. In addition, H2S donors have also been shown to induce analgesia through μ-opioid receptors. Based on the studies, it is thought that the combination of H2S with opioid receptor agonists may provide an additive or even synergistic analgesic effect. It is estimated that the modification of H2S, with currently used analgesic drugs to prevent various side ef- fects and increase analgesic effects, is a promising and wise approach.

Keywords

Hydrogen sulfide, Pain, Analgesic effect

References

• Aydın, O. N. (2002). Ağrı ve ağrı mekanizmalarına güncel bakış [Current inspect to pain and the pain mechanism]. ADÜ Tıp Fakül- tesi Dergisi, 3(2), 37-48.
• Batallé, G., Cabarga, L., & Pol, O. (2020). The inhibitory effects of slow-releasing hydrogen sulfide donors in the mechanical allo- dynia, grip strength deficits, and depressive-like behaviors associ- ated with chronic osteoarthritis pain. Antioxidants, 9(1), 31.
• Cabarga, L., Batallé, G., & Pol, O. (2020). Treatment with slow- releasing hydrogen sulfide donors inhibits the nociceptive and depressive-like behaviours accompanying chronic neuropathic pain: Endogenous antioxidant system activation. Journal of Psy- chopharmacology, 34(7), 737-749.
• Caliendo, G., Cirino, G., Santagada, V., & Wallace, J. L. (2010). Syn-thesis and biological effects of hydrogen sulfide (H2S): develop- ment of H2S-releasing drugs as pharmaceuticals. Journal of Me- dicinal Chemistry, 53(17), 6275-6286.
• Cenac, N., Castro, M., Desormeaux, C., Colin, P., Sie, M., Ranger, M., & Vergnolle, N. (2016). A novel orally administered trimebutine compound (GIC‐1001) is anti‐nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide‐releasing ca- pacity in mice. European Journal of Pain, 20(5), 723-730.
• Cetin, Z., Gunduz, O., Topuz, R. D., Dokmeci, D., Karadag, H. C., & Ulugol, A. (2021). The Role of Hydrogen Sulfide in the Develop- ment of Tolerance and Dependence to Morphine in Mice. Neuro- psychobiology, 80(3), 264-270.
• Cunha, T. M., Dal-Secco, D., Verri Jr, W. A., Guerrero, A. T., Souza,G. R., Vieira, S. M., ... & Cunha, F. Q. (2008). Dual role of hydrogen sulfide in mechanical inflammatory hypernociception. Euro- pean journal Journal of pharmacologyPharmacology, 590(1-3), 127-135.
• Cury, Y., Picolo, G., Gutierrez, V. P., & Ferreira, S. H. (2011). Pain and analgesia: The dual effect of nitric oxide in the nociceptive sys- tem. Nitric oxide, 25(3), 243-254.
• De Cicco, P., Panza, E., Ercolano, G., Armogida, C., Sessa, G., Pirozzi, G., ... & Ianaro, A. (2016). ATB-346, a novel hydrogen sulfide-releas- ing anti-inflammatory drug, induces apoptosis of human mela- noma cells and inhibits melanoma development in vivo. Pharma- cological research, 114, 67-73.
• Distrutti, E. (2011). Hydrogen sulphide and pain. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy)(Discontinued), 10(2), 123-132.
• Distrutti, E., Sediari, L., Mencarelli, A., Renga, B., Orlandi, S., An- tonelli, E., ... & Fiorucci, S. (2006). Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by acti- vating KATP channels. Journal of Pharmacology and Experimental Therapeutics, 316(1), 325-335.
• Donatti, A. F., Araujo, R. M., Soriano, R. N., Azevedo, L. U., Leite- Panissi, C. A., & Branco, L. G. (2014). Role of hydrogen sulfide in the formalin-induced orofacial pain in rats. European journal of pharmacology, 738, 49-56.
• Elies, J., Scragg, J. L., Boyle, J. P., Gamper, N., & Peers, C. (2016). Reg- ulation of the T‐type Ca2+ channel Cav3. 2 by hydrogen sulfide: emerging controversies concerning the role of H2S in nocicep- tion. The Journal of physiology, 594(15), 4119-4129.
• Erol, K., ÜNELÜnel, Ç. Ç., Ayaz, M., Yeşiltuna, E., Demir, E., Dalçınar, H., & Özcan, B. Dipiron’un Analjezik Aktivitesi Üzerine H2S’in Et- kilerinin Sıçanlarda Araştırılması [The Effects of H2S on the Anal- gesic Activity of Dipyrone in Rats]. Türk Tıp Öğrencileri Araştırma Dergisi, 2(2), 90-96.
• Fonseca, M. D., Cunha, F. Q., Kashfi, K., & Cunha, T. M. (2015). NOSH‐aspirin (NBS‐1120), a dual nitric oxide and hydrogen sul- fide‐releasing hybrid, reduces inflammatory pain. Pharmacology research & perspectives, 3(3).
• Fukami, K., Sekiguchi, F., & Kawabata, A. (2017). Hydrogen sulfide and T-type Ca2+ channels in pain processing, neuronal differ- entiation and neuroendocrine secretion. Pharmacology, 99(3-4), 196-203.
• Gomes, F. I. F., Cunha, F. Q., & Cunha, T. M. (2020). Peripheral nitric oxide signaling directly blocks inflammatory pain. Biochemical pharmacology, 176, 113862.
• Guo, J., Li, G., & Yang, L. (2020). Role of H2S in pain: Growing evidences of mystification. European Journal of Pharmacology, 173322.
• Gyöngyösi, A., Verner, V., Bereczki, I., Kiss-Szikszai, A., Zilinyi, R., Tó- saki, Á., ... & Lekli, I. (2021). Basic Pharmacological Characteriza- tion of EV-34, a New H2S-Releasing Ibuprofen Derivative. Mol- ecules, 26(3), 599.
• Huang, C. W., & Moore, P. K. (2015). H 2 S synthesizing enzymes: biochemistry and molecular aspects. Chemistry, biochemistry and pharmacology of hydrogen sulfide, 3-25.
• Kashfi, K., Chattopadhyay, M., & Kodela, R. (2015). NOSH-sulindac (AVT-18A) is a novel nitric oxide-and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflamma- tory, analgesic, antipyretic, anti-platelet, and anti-cancer proper- ties. Redox biologyBiology, 6, 287-296.
• Kida, K., Marutani, E., Nguyen, R. K., & Ichinose, F. (2015). Inhaled hydrogen sulfide prevents neuropathic pain after peripheral nerve injury in mice. Nitric Oxide, 46, 87-92.
• Kimura, H. (2019). Signaling by hydrogen sulfide (H2S) and poly- sulfides (H2Sn) in the central nervous system. Neurochemistry In- ternational, 126, 118-125.
• Kimura, H., (2011). Hydrogen sulfide: its production and functions.Experimental Physiology, 96, 833-835.
• Kolluru, G. K., Shen, X., & Kevil, C. G. (2013). A tale of two gases: NO and H2S, foes or friends for life?. Redox Biology, 1(1), 313-318.
• Koroleva, K., Ermakova, E., Mustafina, A., Giniatullina, R., Giniatullin, R., & Sitdikova, G. (2020). Protective effects of hydrogen sulfide against the atp-induced meningeal nociception. Frontiers in cel- lular Cellular neuroscienceNeuroscience, 14, 266.
• Koroleva, K., Mustafina, A., Yakovlev, A., Hermann, A., Giniatullin, R., & Sitdikova, G. (2017). Receptor mechanisms mediating the pro- nociceptive action of hydrogen sulfide in rat trigeminal neurons and meningeal afferents. Frontiers in cellular neuroscience, 11, 226.
• Li, H., Liu, S., Wang, Z., Zhang, Y., & Wang, K. (2020). Hydrogen sul- fide attenuates diabetic neuropathic pain through NO/cGMP/ PKG pathway and μ-opioid receptor. Experimental Biology and Medicine, 245(9), 823-834.
• Lucarini, E., Micheli, L., Trallori, E., Citi, V., Martelli, A., Testai, L., ... & Di Cesare Mannelli, L. (2018). Effect of glucoraphanin and sul- foraphane against chemotherapy‐induced neuropathic pain: Kv7 potassium channels modulation by H2S release in vivo. Phyto- therapy Research, 32(11), 2226-2234.
• Mannelli, L. D. C., Lucarini, E., Micheli, L., Mosca, I., Ambrosino, P., Soldovieri, M. V., ... & Ghelardini, C. (2017). Effects of natural and synthetic isothiocyanate-based H2S-releasers against chemo- therapy-induced neuropathic pain: Role of Kv7 potassium chan- nels. Neuropharmacology, 121, 49-59.
• Matsui, K., Tsubota, M., Fukushi, S., Koike, N., Masuda, H., Kasanami, Y., ... & Kawabata, A. (2019). Genetic deletion of Cav3. 2 T-type cal- cium channels abolishes H2S-dependent somatic and visceral pain signaling in C57BL/6 mice. Journal of Pharmacological Sci- ences, 140(3), 310-312.
• Matsunami, M., Miki, T., Nishiura, K., Hayashi, Y., Okawa, Y., Nishika- wa, H., ... & Kawabata, A. (2012). Involvement of the endogenous hydrogen sulfide/Cav3. 2 T‐type Ca2+ channel pathway in cys- titis‐related bladder pain in mice. British Journal of Pharmacol- ogy, 167(4), 917-928.
• Melo, I. S., Rodrigues, F. F., Costa, S. O., Braga, A. V., Morais, M. Í., Vaz, J. A., ... & Machado, R. R. (2019). 4-Methylbenzenecarbothio- amide, a hydrogen sulfide donor, inhibits tumor necrosis factor-α and CXCL1 production and exhibits activity in models of pain and inflammation. European Journal of Pharmacology, 856, 172404.
• Miclescu, A., & Gordh, T. (2009). Nitric oxide and pain:‘Something old, something new’. Acta Anaesthesiologica Scandinavica, 53(9), 1107-1120.
• Ocaña, M., Cendán, C. M., Cobos, E. J., Entrena, J. M., & Baeyens,J. M. (2004). Potassium channels and pain: present realities and future opportunities. European Journal of Pharmacology, 500(1-3), 203-219.
• Oguma, N., Takahashi, K., Okabe, S., & Ohta, T. (2021). Inhibitory effect of polysulfide, an endogenous sulfur compound, on oxi-dative stress-induced TRPA1 activation. Neuroscience Letters, 757, 135982.
• Okamoto, M., Yamaoka, M., Ando, T., Takei, M., Taniguchi, S., Tera- bayashi, T., ... & Kimura, T. (2014). P52 Endogenous hydrogen sul- fide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabe- tes. Nitric Oxide, 39, S31-S32.
• Orr, P. M., Shank, B. C., & Black, A. C. (2017). The role of pain clas- sification systems in pain management. Critical Care Nursing Clin- ics, 29(4), 407-418.
• Pozsgai, G., Bátai, I. Z., & Pintér, E. (2019). Effects of sulfide and polysulfides transmitted by direct or signal transduction‐medi- ated activation of TRPA1 channels. British Journal of Pharmacol- ogy, 176(4), 628-645.
• Predmore, B. L., Lefer, D. J., & Gojon, G. (2012). Hydrogen sulfide in bio- chemistry and medicine. Antioxidants & Redox Signaling, 17(1), 119-140.
• Przewłocki, R., & Przewłocka, B. (2001). Opioids in chronic pain. Eu- ropean Journal of Pharmacology, 429(1-3), 79-91.
• Qabazard, B., Masocha, W., Khajah, M., & Phillips, O. A. (2020). H2S donor GYY4137 ameliorates paclitaxel-induced neuropathic pain in mice. Biomedicine & Pharmacotherapy, 127, 110210.
• Roa-Coria, J. E., Pineda-Farias, J. B., Barragán-Iglesias, P., Quiñonez- Bastidas, G. N., Zúñiga-Romero, Á., Huerta-Cruz, J. C., ... & Rocha- González, H. I. (2019). Possible involvement of peripheral TRP channels in the hydrogen sulfide-induced hyperalgesia in dia- betic rats. BMC Neuroscience, 20(1), 1-17
• Rose, P., Moore, P. K., & Zhu, Y. Z. (2017). H 2 S biosynthesis and catabolism: new insights from molecular studies. Cellular and Mo- lecular Life Sciences, 74(8), 1391-1412.
• Schmidtko, A., Tegeder, I., & Geisslinger, G. (2009). No NO, no pain? The role of nitric oxide and cGMP in spinal pain processing. Trends in Neurosciences, 32(6), 339-346.
• Shefa, U., Yeo, S. G., Kim, M. S., Song, I. O., Jung, J., Jeong, N. Y., & Huh, Y. (2017). Role of gasotransmitters in oxidative stresses, neu- roinflammation, and neuronal repair. BioMed research Research International, 2017, 1-15.
• Tang, G., Wu, L., & Wang, R. (2010). Interaction of hydrogen sulfide with ion channels. Clinical and Experimental Pharmacology and Physiology, 37(7), 753-763.
• Tsantoulas, C., & McMahon, S. B. (2014). Opening paths to novel analgesics: the role of potassium channels in chronic pain. Trends in Neurosciences, 37(3), 146-158.
• Tsubota, M., & Kawabata, A. (2019). Regulation of Cav3. 2-medi- ated pain signals by hydrogen sulfide. Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 154(3), 128-132.
• Verma, R., Akhtar, Y., & Singh, S. (2017). A review of patents on therapeutic potential and delivery of hydrogen sulfide. Recent Patents on Drug Delivery & Formulation, 11(2), 114-123.
• Wallace, J. L. (2007). Hydrogen sulfide-releasing anti-inflammato- ry drugs. Trends in Pharmacological Sciences, 28(10), 501-505.
• Wallace, J. L., Vaughan, D., Dicay, M., MacNaughton, W. K., & de Nucci, G. (2018). Hydrogen sulfide-releasing therapeutics: transla- tion to the clinic. Antioxidants & redox signaling, 28(16), 1533-1540.
• Wang, R. U. I. (2002). Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter?. The FASEB jour- nal, 16(13), 1792-1798.
• Xu, X., Li, S., Shi, Y., Tang, Y., Lu, W., Han, T., ... & Liu, C. (2019). Hydro- gen sulfide downregulates colonic afferent sensitivity by a nitric oxide synthase‐dependent mechanism in mice. Neurogastroen- terology & Motility, 31(1), e13471.
• Yang, H. Y., Wu, Z. Y., Wood, M., Whiteman, M., & Bian, J. S. (2014). Hydrogen sulfide attenuates opioid dependence by suppression of adenylate cyclase/cAMP pathway. Antioxidants & Redox Signal- ing, 20(1), 31-41.
• Zheng, Y., Liao, F., Lin, X., Zheng, F., Fan, J., Cui, Q., ... & Cai, J. (2017). Cystathionine γ-Lyase–Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby increasing osteo- blast activity to promote bone fracture healing. Antioxidants & Redox Signaling, 27(11), 742-753.
• Zhuang, L., Li, K., Wang, G., Shou, T., Gao, C., Mao, Y., ... & Zhao, M. (2018). Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gam- ma/p38/Jun N-terminal kinase pathway. Experimental Biology and Medicine, 243(1), 57-65.