Brazilian Journal of Pain
https://brjp.org.br/article/doi/10.5935/2595-0118.20200038
Brazilian Journal of Pain
Original Article

Evaluation of the keratinocytes or fibroblasts culture supernatant in an inflammatory hyperalgesia model

Avaliação do sobrenadante da cultura de queratinócitos ou fibroblastos em modelo de hiperalgesia inflamatória

Cíntia Ávila Souza; Gilson Gonçalves dos Santos; Felipe Hertzing Farias; Eli Ávila Souza Júnior; Carlos Amilcar Parada

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Abstract

BACKGROUND AND OBJECTIVES: Inflammation is a defense response of the body to a cellular damage caused by physical, chemical or biological agents, which triggers, among other factors, pain. Although inflammation plays an important role in the protection and regeneration of tissue injury, inflammatory pain results in decreased quality of life. In view of this, the development of safe and less invasive forms for the treatment of inflammatory pain is of great importance. The objective of this study was to evaluate the antihyperalgesic potential of the culture supernatant of keratinocytes and human fibroblasts in an experimental model of inflammatory hyperalgesia.

METHODS: Evaluation of carrageenan induced inflammatory hyperalgesia through the use of electronic von Frey in animal models treated with culture supernatant of keratinocytes and fibroblasts.

RESULTS: Local administration of naloxone, a nonselective opioid antagonist, in peripheral tissue, has been observed to inhibit the antihyperalgesic effect of the keratinocyte culture supernatant. Fibroblast culture supernatant on days 1 and 3 reverses for 2 hours the carrageenan induced inflammatory hyperalgesia, which is mediated by µ opioid agonist.

CONCLUSION: This study indicates that culture supernatant of fibroblasts and keratinocytes is capable of inducing antinociception in inflammatory hyperalgesia, mediated by the release of endogenous opioids. In addition, it has been observed that the analgesic effect of the fibroblast culture supernatant is mediated specifically by the µ opioid agonist, having a duration of 2 hours.

Keywords

Analgesia, Fibroblasts, Keratinocytes, Peripheral nervous system, Skin

Resumo

JUSTIFICATIVA E OBJETIVOS: A inflamação é uma resposta de defesa do organismo a uma lesão celular causada por agentes físicos, químicos ou biológicos, a qual desencadeia, entre outros fatores, a dor. Apesar da inflamação possuir um importante papel na proteção e regeneração da lesão tecidual, a dor inflamatória culmina na diminuição da qualidade de vida. Diante disso, é de grande importância o desenvolvimento de formas seguras e menos invasivas para o tratamento da dor inflamatória. O objetivo deste estudo foi avaliar o potencial anti-hiperalgésico do sobrenadante de cultura de queratinócitos e fibroblastos humanos em modelo experimental de hiperalgesia inflamatória.

MÉTODOS: Avaliação da hiperalgesia inflamatória induzida por carragenina através do uso de von Frey eletrônico em modelos animais tratados com sobrenadante de cultura de queratinócitos e fibroblastos.

RESULTADOS: Observou-se que a administração local de naloxona, antagonista opioide não seletivo, em tecido periférico inibiu o efeito anti-hiperalgésico do sobrenadante da cultura de queratinócitos. Sobrenadante de cultura de fibroblastos dos dias 1 e 3 reverte por 2h a hiperalgesia inflamatória induzida por carragenina, sendo esta mediada por agonista µ opioide.

CONCLUSÃO: Este estudo indicou que sobrenadante de cultura de fibroblastos e queratinócitos foi capaz de induzir antinocicepção em hiperalgesia inflamatória, mediada pela liberação de opioides endógenos. Além disso, foi observado que o efeito analgésico do sobrenadante de cultura de fibroblastos é mediado especificamente por agonista µ opioide, tendo uma duração de 2 horas.

Palavras-chave

Analgesia, Fibroblastos, Pele, Queratinócitos, Sistema nervoso periférico

References

Abbas AK, Janeway Jr CA. Immunology: improving on nature in the twenty-first century. Cell. 2000;100(1):129-38.

Dawes JM, Anderson DA, Bennett DL, Bevan S, McMahon SB. Inflammatory mediators and modulators of pain. Wall and Melzack's Textbook of Pain. 2013;6:48-67.

Levine JD, Taiwo Y. Inflammatory Pain. Textbook of Pain. 1994.

Carvalho MMMJ. O Sofrimento da dor em câncer. Introdução à psiconcologia. 2003:103-8p.

Messlinger K. What is a nociceptor?. Anaesthesist. 1997;46(2):142-53.

Besson JM. The complexity of physiopharmacologic aspects of pain. Drugs. 1997;53(Suppl.2):1-9.

Webster KE. Somaesthetic pathways. Br Med Bull. 1977;33(2):113-20.

Woolf CJ. Recent advances in the pathophysiology of acute pain. Br J Anaesth. 1989;63(2):139-46.

Stein C, Pflüger M, Yassouridis A, Hoelzl J, Lehrberger K, Welte C. No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia. J Clin Invest. 1996;98(3):793-9.

Stein C, Gramsch C, Herz A. Intrinsic mechanisms of antinociception in inflammation: local opioid receptors and beta-endorphin. J Neurosci. 1990;10(4):1292-8.

Garcia JB, Cardoso MG, Dos-Santos MC. Opioids and the immune system: clinical relevance. Rev Bras Anestesiol. 2012;62(5):709-18.

Slominski AT, Zmijewski MA, Skobowiat C, Zbytek B, Slominski RM, Steketee JD. Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system. Adv Anat Embryol Cell Biol. 2012;212:v-155.

Vetter I, Kapitzke D, Hermanussen S, Monteith GR, Cabot PJ. The effects of pH on beta-endorphin and morphine inhibition of calcium transients in dorsal root ganglion neurons. J Pain. 2006;7(7):488-99.

Hollt V. Opioid peptide processing and receptor selectivity. Annu Rev Pharmacol Toxicol. 1986;26(1):59-77.

Nakanishi S, Inoue A, Kita T, Nakamura M, Chang AC, Cohen SN. Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor. Nature. 1979;278(5703):423-7.

Sibinga NE, Goldstein A. Opioids peptides and opioid receptors in cell of the immune system. Annu Rev Immunol. 1988;6:219-49.

Wintzen M, Yaar M, Avila E, Vermeer BJ, Gilchrest BA. Keratinocytes produce b-endorphin and b-lipotropic hormone after stimulation by UV, IL-1a or phorbol esters. J Invest Dermatol. 1995;104:641.

Schauer E, Trautinger F, Köck A, Schwarz A, Bhardwaj R, Simon M. Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes. J Clin Invest. 1994;93(5):2258-62.

Bigliardi PL, Bigliardi-Qi M, Buechner S, Rufli T. Expression of mµ-opiate receptor in human epidermis and keratinocytes. J Invest Dermatol. 1998;111(2):297-301.

Lo HH, Tseng LF, Wei E, Li CH. Endorphin is a potent analgesic agent. Proc Natl Acad Sci. 1976;7(8):2895-8.

Slominski AT, Zmijewski MA, Zbytek B, Brozyna AA, Granese J, Pisarchik A. Regulated proenkephalin expression in human skin and cultured skin cells. J Invest Dermatol. 2011;131(3):613-22.

Bigliardi-Qi M, Sumanovski LT, Büchner S, Rufli T, Bigliardi PL. Mu-opiate receptor and beta-endorphin expression in nerve endings and keratinocytes in human skin. Dermatology. 2004;209(3):183-9.

Schaible HG. Pathophysiology of pain. Orthopade. 2006;36(1):8-16.

Schaible HG. Peripheral and central mechanisms of pain generation. Hand Exp Pharmacol. 2007:3-28.

Siderov J, Zalcberg JR. Prescribing opioids--a painful experience. Med J Aust. 1994;161(9):515-6.

Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N. Opioid complications and side effects. Pain Physician. 2008;11(2 Suppl):S105-20.

Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(14):276-86.

Eriksen J, Sjogren P, Bruera E, Ekholm O, Rasmussen NK. Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain. 2006;125(1-2):172-9.

Vivancos GG, Verri Jr WA, Cunha TM, Schivo IR, Parada CA, Cunha FQ. An electronic pressure-meter nociception paw test for rats. Braz J Med Biol Res. 2004;37(3):391-9.

Rosland JH. The formalin test in mice: the influence of ambient temperature. Pain. 1991;45(2):211-6.

Henriques MG, Silva PM, Martins MA, Flores CA, Cunha FQ, Assreuy-Filho J. Mouse paw edema. A new model for inflammation?. Braz J Med Biol Res. 1987;20(2):243-9.

Bodnar RJ. Endogenous opiates and behavior: 2017. Peptides. 2020;124:170223.

Leong C, Neumann C, Ramasamy S, Rout B, Wee LY, Bigliardi-Qi M. Investigating endogenous µ-opioid receptors in human keratinocytes as pharmacological targets using novel fluorescent ligand. PloS one. 2017;12(12).

Li X, Zhu J, Tao Y, Tao K. Elevated endogenous opioids in obstructive jaundice: the possible skin mechanisms. Med Hypotheses. 2018;116:119-21.


Submitted date:
02/20/2020

Accepted date:
05/10/2020

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