Targeting Endothelin Receptors: A Promising Strategy for Alleviating Cancer-Related and Non-Cancer Pain in Animal Models | [Pakistan Veterinary Journal • 2024]

Author(s):

1. Muhammad Mohsin: Shantou University Medical College,Shantou, Guangdong Province 515041,China

2. Yusra Afzal: Government College Women University Faisalabad,,Pakistan

3. Bo-Ya Hu: Shantou University Medical College,Shantou, Guangdong Province 515041,China

4. Zuo-Jie Jiang: Shantou University Medical College,Shantou, Guangdong Province 515041,China

5. Peng-Bo Jing: Shantou University Medical College,Shantou, Guangdong Province 515041,China

6. Hao-Hao Chen: Shantou University Medical College,Shantou, Guangdong Province 515041,China

7. Muhammad Tahir Aleem: Shantou University Medical College,Shantou, Guangdong Province 515041,China

8. Ashiq Ali: Shantou University Medical College,Shantou, Guangdong Province 515041,China

9. Shahbaz Ul Haq: Shantou University Medical College,Shantou, Guangdong Province 515041,China

10. Shakeel Ahmed: Shantou University Medical College, Shantou, Guangdong Province 515041, China; Shaheed Benazir Bhutto University of Veterinary and Animal Sciences Sakrand, Sind, Pakistan

11. Mohsan Ullah Goraya: School of Medicine, Huaqiao University Quanzhou,Quanzhou,China

12. Bilal Murtaza: School of Bioengineering, Dalian University of Technology,Dalian,China

13. Asghar Abbas: Department of Veterinary and Animal Sciences, Muhammad Nawaz Sharif University of Agriculture Multan,,Pakistan

14. Kashif Hussain: Department of Veterinary and Animal Sciences, Muhammad Nawaz Sharif University of Agriculture Multan,,Pakistan

15. Fen-Fei Gao: Shantou University Medical College,Shantou, Guangdong Province 515041,China

16. Xing-Jun Liu: Shantou University Medical College, Shantou, Guangdong Province 515041, China; School of Pharmacy, Nantong University, Nantong, Jiangsu Province 226001, China

Abstract:

Endothelin is a potent vasoconstrictor known to play a role in various painful conditions. This study aims to explore the role of the endothelin system, including its receptors, isoforms, and converting enzymes, in the pathogenesis of cancerous and non-cancerous ailments. Additionally, it evaluates the efficacy of endothelin receptor antagonists in managing pain associated with these conditions. A review of recent studies was conducted to identify the fundamental activities of the endothelin system and the impact of antagonists targeting endothelin receptors on pain relief. The endothelin system has emerged as a crucial player in various painful conditions. Antagonists targeting endothelin receptors have shown promise in alleviating cancer pain, with endothelin secretion observed in cancer cells of diverse histologic types. Moreover, endothelin receptor antagonists have demonstrated potential in managing neuropathic and inflammatory pain syndromes. Therapies targeting the endothelin system, particularly endothelin receptor antagonists, hold significant promise for managing both cancer-related and non-cancer-related pain syndromes, highlighting the therapeutic potential of these agents in pain management.

Page(s): 555-562

DOI: 10.29261/pakvetj/2024.208

Published: Journal: Pakistan Veterinary Journal, Volume: 44, Issue: 3, Year: 2024

Keywords:

Cancer pain Endothelins ET1 Non cancer pain

References:

[1] Afzal Z,Javed MT,Mohsin M .2023 .The usefulness of glutaraldehyde coagulation test as a conjuncture test in the diagnosis of tuberculosis in humans and animals. Agrobiol Rec, 15 : 34-40.

[2] Aley KO,Reichling DB,Levine JD .1996 .Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans. Neuroscience, 73(1) : 259-65.

[3] Ali A,Manzoor MF,Ahmad N .2022 .The burden of cancer, government strategic policies, and challenges in Pakistan: A comprehensive review. Front Nutr, 22 : 940514.

[4] Angeli F,Verdecchia P,Reboldi G .2021 .Aprocitentan, a dual endothelin receptor antagonist under development for the treatment of resistant hypertension. Cardiol Ther, 10 : 397-406.

[5] Arndt PF,Turkowski K,Cekay MJ K .2024 .Endothelin and the tumor microenvironment: a finger in every pie. Clin Sci, 138(11) : 617-34.

[6] Baamonde A,Lastra A,Villazón M .2004 .Involvement of endogenous endothelins in thermal and mechanical inflammatory hyperalgesia in mice. Naunyn Schmiedebergs Arch Pharmacol, 369 : 245-251.

[7] Bae EH,Greenwald MK,Schwartz AG .2021 .Chemotherapyinduced peripheral neuropathy: mechanisms and therapeutic avenues. Neurotherapeutics, 1(4) : 2384-96.

[8] Banecki KM,Dora KA .2023 .. in Health and Disease. Int J Mol Sci, 24(14) : 11295.

[9] Bhalla S,Pais G,Tapia M .2015 .Endothelin ETA receptor antagonist reverses naloxone-precipitated opioid withdrawal in mice. Can J Physiol Pharmacol, 93(11) : 935-944.

[10] Bolli MH,Boss C,Binkert C .2012 .-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem, 55(17) : 7849-7861.

[11] Briyal S,Ranjan AK,Hornick MG .2019 .Anti-apoptotic activity of ETB receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia. Sci Rep, 9(1) : 10439.

[12] Cain DM,Wacnik PW,Turner M .2001 .Functional interactions between tumor and peripheral nerve: changes in excitability and morphology of primary afferent fibers in a murine model of cancer pain. J Neurosci, 21(23) : 9367-9376.

[13] Chen W,Liu P,Zhao YL .2022 .Clinico-pathological, immunohistochemical and in-situ Tunel assay observations of canine breast tumors. Pak Vet J, 42(1) : 131-1134.

[14] Chen HH,Mohsin M,Ge JY .2023 .Optogenetic Activation of Peripheral Somatosensory Neurons in Transgenic Mice as a Neuropathic Pain Model for Assessing the Therapeutic Efficacy of Analgesics. ACS Pharmacol Transl Sci, 13(1) : 236-48.

[15] D'Orléans-Juste P,Ndunge OB,Desbiens L .2019 .Endothelins in inflammatory neurological diseases. Pharmacol Therapeut, 194 : 145-160.

[16] Davenport A,Kuc R,Southan C .2018 .New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine. Physiol. Res, 2 : 67.

[17] Davenport AP,Hyndman KA,Dhaun N .2016 .. Pharmacol Rev, 68(2) : 357-418.

[18] Di Maio G,Villano I,Ilardi CR .2023 .Mechanisms of Transmission and Processing of Pain: A Narrative Review. Int J Environ Res Public Health, 20(4) : 3064.

[19] Ding Y,Ting JP,Liu J .2020 .Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics. Amino Acids, 52(9) : 1207-26.

[20] Don G,Joseph F,Celermajer D .2012 .Ironic case of hepatic dysfunction following the global withdrawal of sitaxentan. Intern Med J, 42(12) : 1351-1354.

[21] Enevoldsen FC,Sahana J,Wehland M .2020 .Endothelin receptor antagonists: status quo and future perspectives for targeted therapy. J Clin Med, 9(3) : 824.

[22] Evans NJ,Walker JW .2008 .Sustained Ca2+ signaling and delayed internalization associated with endothelin receptor heterodimers linked through a PDZ finger. Can J Physiol Pharmacol, 86(8) : 526-535.

[23] Filep JG,Sirois MG,Rousseau A .1991 .Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor. Br J Pharmacol, 104(4) : 797-804.

[24] Furukawa A,Shinoda M,Kubo A .2018 .Endothelin signaling contributes to modulation of nociception in early-stage tongue cancer in rats. Anesthesiology, 128(6) : 1207-1219.

[25] Griswold DE,Douglas SA,Martin LD .1999 .Endothelin B receptor modulates inflammatory pain and cutaneous inflammation. Mol Pharmacol, 56(4) : 807-812.

[26] Hans G,Schmidt BL,Strichartz G .2009 .Nociceptive sensitization by endothelin-1. Brain Res Rev, 60(1) : 36-42.

[27] Haroun R,Wood JN,Sikandar S .2023 .Mechanisms of cancer pain. Front Pain Res, 3 : 1030899.

[28] Haryono A,Ramadhiani R,Ryanto R .2022 .Endothelin and the cardiovascular system: The long journey and where we are going. Biol, 11(5) : 759.

[29] Haynes WG,Strachan FE,Webb DJ .1995 .Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation, 92(3) : 357-363.

[30] Hong JI,Park IY,Kim HA .2020 .Understanding the molecular mechanisms underlying the pathogenesis of arthritis pain using animal models. Int J Mol Sci, 14(2) : 533.

[31] Ihara M,Saeki T,Fukuroda T .1992 .A novel radioligand [125I] BQ-3020 selective for endothelin (ETB) receptors. Life Sci, 51(6) : PL47-PL52.

[32] Jarvis MF,Wessale JL,Zhu CZ .2000 .an endothelin ETA receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain. Eur J Pharmacol, 388(1) : 29-35.

[33] Johnström P,Rudd JH,Richards HK .2006 .Imaging endothelin ETB receptors using [18F]-BQ3020: in vitro characterization and positron emission tomography (microPET). Exp Biol Med, 231(6) : 736-740.

[34] Khodorova A,Montmayeur J-P and Strichartz G .2009 .Endothelin receptors and pain. J Pain, 10(1) : 4-28.

[35] Khodorova A,Navarro B,Jouaville LS .2003 .Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nat Med, 9(8) : 1055-1061.

[36] Koyama Y .2021 .Endothelin ETB receptor-mediated astrocytic activation: pathological roles in brain disorders. Int J Mol Sci, 22(9) : 4333.

[37] Lam DK,Dang D,Zhang J .2012 .Novel animal models of acute and chronic cancer pain: a pivotal role for PAR2. J Neurosci, 32(41) : 14178-14183.

[38] Lindsay TH,Jonas BM,Sevcik MA .2005 .Pancreatic cancer pain and its correlation with changes in tumor vasculature, macrophage infiltration, neuronal innervation, body weight and disease progression. Pain, 119(1-3) : 233-246.

[39] Lutz BM,Wu S,Gu X .2018 .Endothelin type A receptors mediate pain in a mouse model of sickle cell disease. Haematologica, 103(7) : 1124.

[40] Maaruf NA,Najjar SM,Ali SA,Pak Vet J .2023 .Anatomical and Histopathological Comparative Studies Between Right and Left Mammary Tumors in a Rat Model Induced by DMBA. , 1(2) : .

[41] Malfait AM,Miller RE,Block JA .2020 .Targeting neurotrophic factors: novel approaches to musculoskeletal pain. Pharmacol Therapeut, 1 : 107553.

[42] Masuda Y,Sugo T,Kikcuhi T,aspartyl-D- T .1996 .-(2-thienyl) glycyl-L-leucylD-tryptophyl] disodium salt], in human endothelinA and endothelinB receptors. J Pharmacol, 279(2) : 675-685.

[43] Matsuda M,Huh Y,Ji RR .2019 .Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain. J Anesth, 20 : 131-9.

[44] Nabal M,Librada S,Redondo MJ .2012 .The role of paracetamol and nonsteroidal anti-inflammatory drugs in addition to WHO Step III opioids in the control of pain in advanced cancer. A systematic review of the literature. Palliat Med, 26(4) : 305-312.

[45] Nagamine K,Ozaki N,Shinoda M .2006 .Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats. J Pain, 7(9) : 659-670.

[46] Nappi F,Fiore A,Masiglat J .2022 .Endothelium-derived relaxing factors and endothelial function: A systematic review. Biomed, 10(11) : 2884.

[47] Nozaki-Taguchi N,Chaplan SR,Higuera ES .2001 .Vincristineinduced allodynia in the rat. Pain, 93(1) : 69-76.

[48] Palmer J,Kehoe P,Love S .2010 .Endothelin‐converting enzyme‐1 in Alzheimer's disease and vascular dementia. Neuropath Appl Neuro, 36(6) : 487-497.

[49] Love Palmer J,S Palmer J .2011 .Endothelin receptor antagonists: potential in Alzheimer's disease. Pharmacol Res, 63(6) : 525-531.

[50] Patel K,Walport LJ,Walshe JL .2020 .Cyclic peptides can engage a single binding pocket through highly divergent modes. Proc Natl Acad Sci, 117(43) : 26728-38.

[51] Perreault T,Baribeau J .1995 .Characterization of endothelin receptors in newborn piglet lung. Am J Physiol Lung Cell Mol Physiol 268, (4) : L607-L614.

[52] Peters C,Lindsay T,Pomonis J .2004 .Endothelin and the tumorigenic component of bone cancer pain. Neuroscience, 126(4) : 1043-1052.

[53] Pickering V,Gupta RJ,Quang P .2008 .Effect of peripheral endothelin-1 concentration on carcinoma-induced pain in mice. Eur J Pain, 12(3) : 293-300.

[54] Pickering V,Jordan RC,Schmidt BL .2007 .Elevated salivary endothelin levels in oral cancer patients-a pilot study. Oral Oncol, 43(1) : 37-41.

[55] Piovezan AP,D'Orleans-Juste P,Tonussi C .1997 .Endothelins potentiate formalin-induced nociception and paw edema in mice. Can J Physiol Pharmacol, 75(6) : 596-600.

[56] Pomonis JD,Rogers SD,Peters CM .2001 .Expression and localization of endothelin receptors: implications for the involvement of peripheral glia in nociception. J Neurosci, 21(3) : 999-1006.

[57] Polomano RC,Bennett GJ .2001 .Chemotherapy-evoked painful peripheral neuropathy. Pain Med, 2(1) : 8-14.

[58] Quang PN,Schmidt BL .2010 .Endothelin-A receptor antagonism attenuates carcinoma-induced pain through opioids in mice. J Pain, 11(7) : 663-671.

[59] Russell FD,Davenport AP .1996 .Characterization of the binding of endothelin ETB selective ligands in human and rat heart. Br J Pharmacol, 119(4) : 631-636.

[60] Saini A,Kumar M,Bhatt S .2020 .Cancer causes and treatments. Int J Pharm Sci Res, 11 : 3121-34.

[61] Schmidt BL,Pickering V,Liu S .2007 .Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain. Eur J Pain, 11(4) : 406-414.

[62] Smith SB,Crager SE,Mogil JS .2004 .Paclitaxel-induced neuropathic hypersensitivity in mice: responses in 10 inbred mouse strains. Life Sci, 74(21) : 2593-604.

[63] Stubblefield MD .2018 .Cancer rehabilitation: principles and practice. , 28 : .

[64] Symons F,Wendelschafer-Crabb G,Kennedy W .2008 .Evidence of altered epidermal nerve fiber morphology in adults with selfinjurious behavior and neurodevelopmental disorders. Pain, 134 : 354-355.

[65] Takai M,Umemura I,Yamasaki K,- K .1992 .IRL 1620, for the ETB receptor. Biochem Biophys Res Commun, 184(2) : 953-959.

[66] Takayama Y,Derouiche S,Maruyama K .2019 .Emerging perspectives on pain management by modulation of TRP channels and ANO1. Int J Mol Sci, 20(14) : 3411.

[67] Teng L,Gao JF,Zhou L .2016 .Influence of salidroside on expression level of endothelin-1 and its receptors under hypoxic conditions in chicken embryonic pulmonary artery smooth muscle cells. Pak Vet J, 36(2) : 214-218.

[68] Tsagareli MG,Nozadze I,Tsiklauri N .2020 .Thermal hyperalgesia and mechanical allodynia elicited by histamine and nonhistaminergic itch mediators: respective involvement of TRPV1 and TRPA1. Neuroscience, 449 : 35-45.

[69] Tsuda M,Kohro Y,Yano T .2011 .JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain, 134(4) : 1127-1139.

[70] Vatter H and Seifert V .2006 .Ambrisentan, a non‐peptide endothelin receptor antagonist. Cardiovasc drug rev 24, (1) : 63-76.

[71] Vatter H,Zimmermann M,Weyrauch E .2003 .Cerebrovascular characterization of the novel nonpeptide endothelin-A receptor antagonist LU 208075. Clin Neuropharmacol, 26(2) : 73-83.

[72] Verma V,Sheikh Z,Ahmed AS .2015 .Nociception and role of immune system in pain. Acta Neurol Belg, 20 : .

[73] Von Geldern TW,Tasker AS,Sorensen BK .1999 .- carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ETB selectivity. J Med Chem, 42(18) : 3668-3678.

[74] Wang AB,Housley SN,Flores AM .2021 .A review of movement disorders in chemotherapy-induced neurotoxicity. J Neuroeng Rehabil, 18(1) : 16.

[75] Wang L,Wang L,Yan F .2022 .Understanding the molecular mechanism of endothelin ETA receptor selecting endothelin-1 and-3. , 121(13) : 2490-502.

[76] Williams JT,Christie MJ,Manzoni O .2001 .Cellular and synaptic adaptations mediating opioid dependence. Physiol. Rev, 81(1) : 299-343.

[77] Wintzen M,Yaar M,Burbach JP .1996 .Proopiomelanocortin gene product regulation in keratinocytes. J Invest Dermatol, 106(4) : 673-678.

[78] Wood M,,Mitchell JA,Wood EJ .1999 .Endothelin is induced by cytokines in human vascular smooth muscle cells: Evidence for intracellular endothelin-converting enzyme. Mol Pharmacol, 55 : 902-909.

[79] Wu C,Chan MF,Stavros F .1997 .Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist. J Med Chem, 40(11) : 1690-1697.

[80] Yamasaki R,Fujii T,Wang B .2016 .Allergic inflammation leads to neuropathic pain via glial cell activation. J Neurosci, 36(47) : 11929-11945.

[81] Yanagisawa M,Kurihara H,Kimura S .1988 .A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature, 332(6163) : 411-415.

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