Brazilian Journal of Pain
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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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.


Analgesia, Fibroblasts, Keratinocytes, Peripheral nervous system, Skin


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.


Analgesia, Fibroblastos, Pele, Queratinócitos, Sistema nervoso periférico


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