Brazilian Journal of Pain
https://brjp.org.br/article/doi/10.5935/2595-0118.20200004
Brazilian Journal of Pain
Original Article

Effects of duloxetine, fluoxetine and pregabalin on fentanyl-induced hyperalgesia in rattus novergicus

Efeitos da duloxetina, fluoxetina e pregabalina sobre a hiperalgesia induzida por fentanil em rattus novergicus

Oscar César Pires; Maria Luiza Dalcim; Ana Luiza Montes Pigozzi; Fabiana Mara Scarpelli de Lima Alvarenga Caldeira; Marta Helena Rovani Pires; Lafayette de Almeida Neto; Irimar de Paula Posso

http://dx.doi.org/10.5935/2595-0118.20200004 BrJP, vol.3, n1, p.14-18, 2020
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Abstract

BACKGROUND AND OBJECTIVES: Opioids are drugs used to relieve pain, but may cause increased pain sensitivity, known as opioid-induced hyperalgesia, which adversely affects pain management. This study aimed to check if fentanyl, an opioid widely used in the clinical practice, produces hyperalgesia that can be attenuated by duloxetine, fluoxetine and pregabalin.

METHODS: Thirty male Wistar rats were divided into six groups. The animals in group 1 received 1mL of 0.9% saline solution intraperitoneally (IP) and gavage; group 2 received fentanyl at a dose of 100µg.kg-1 IP and 0.9% saline solution per gavage; groups 3, 4 and 5 received fentanyl at the dose of 100µg.kg-1 IP, and gavage with duloxetine, 40mg.kg-1, fluoxetine, 40mg.kg-1 and pregabalin, 40mg.kg-1, respectively. Under general anesthesia with isoflurane, all animals were submitted to plantar surgical incision. The application of Von Frey filaments assessed hyperalgesia at the second hour, one, three, five and seven days after treatment.

RESULTS: Two hours after the procedure, no differences were observed between G1 and G2, although G3, G4, and G5 showed less hyperalgesia. On day one and day three, a greater hyperalgesic effect was observed in G2 when compared to G1, G3, G4 and G5. On day five, there was a hyperalgesic effect on G2, and on day seven, there were no differences among the groups.

CONCLUSION: The results suggest that fentanyl induces hyperalgesia and the efficacy of duloxetine, fluoxetine, and pregabalin in reducing it.

Keywords

Duloxetine, Fentanyl, Fluoxetine, Hyperalgesia, Pregabalin, Rats

Resumo

JUSTIFICATIVA E OBJETIVOS: Opioides são fármacos utilizados para o alívio da dor, porém, podem causar aumento da sensibilidade dolorosa, denominada hiperalgesia induzida por opioides, que afeta negativamente o tratamento da dor. O objetivo deste estudo foi avaliar se o fentanil, opioide amplamente utilizado na prática clínica, produz hiperalgesia que pode ser atenuada pela duloxetina, fluoxetina e pregabalina.

MÉTODOS: Trinta ratos Wistar machos, foram divididos em 6 grupos. No grupo 1, os animais receberam 1mL de solução fisiológica (SF) a 0,9% por via intraperitoneal (IP) e por gavagem; no grupo 2, fentanil na dose de 100µg.kg-1 IP e SF a 0,9% por gavagem; nos grupos 3, 4 e 5 os animais receberam fentanil na dose de 100µg.kg-1 IP e, por gavagem, receberam respectivamente duloxetina, 40mg.kg-1, fluoxetina, 40mg.kg-1 e pregabalina, 40mg.kg-1. A avaliação da hiperalgesia e sua atenuação foi feita pela aplicação de filamentos de Von Frey, na 2ª hora e nos dias 1, 3, 5 e 7, após o tratamento.

RESULTADOS: Na 2ª hora pós-procedimento não foram observadas diferenças entre G1 e G2, entretanto, G3, G4 e G5 se mostraram com menor hiperalgesia. No 1º e 3º dias foi observado maior efeito hiperalgésico em G2 quando comparado com G1, G3, G4 e G5. No 5º dia foi observado efeito hiperalgésico no G2, e no 7º dia não houve diferenças entre os grupos.

CONCLUSÃO: Os resultados sugerem que o fentanil induz hiperalgesia e eficácia da duloxetina, fluoxetina e pregabalina na sua redução.

Palavras-chave

Duloxetina, Fentanil, Fluoxetina, Hiperalgesia, Pregabalina, Ratos

References

Recommended by the IASP subcommittee on taxonomy. Pain. 1979;6(3):249.

Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006;104(3):570-87.

Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations. Clin J Pain. 2008;24(6):479-96.

Silverman SM. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician. 2009;12(3):679-84.

Mao J. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy. Pain. 2002;100(3):213-7.

Vanderah TW, Ossipov MH, Lai J, Malan Jr TP, Porreca F. Mechanisms of opioid-induced pain and antinociceptive tolerance: descending facilitation and spinal dynorphin. Pain. 2001;92(1-2):5-9.

Reznikov I, Pud D, Eisenberg E. Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain. Br J Clin Pharmacol. 2005;60(3):311-8.

Célèrier E, Rivat C, Jun Y, Laulin JP, Larcher A, Reynier P. Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. Anesthesiology. 2000;92(2):465-72.

Simonnet G, Rivat C. Opioid-induced hyperalgesia: abnormal or normal pain?. Neuroreport. 2003;14(1):1-7.

Ossipov MH, Lai J, King T, Vanderah TW, Porreca F. Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers. 2005;80(2-3):319-24.

Gebhart GF. Descending modulation of pain. Neurosci Biobehav Rev. 2004;27(8):729-37.

Li Z, Li C, Yin P, Wang ZJ, Luo F. Inhibition of CaMKIIa in the central nucleus of amygdala attenuates fentanyl-induced hyperalgesia in rats. J Pharmacol Exp Ther. 2016;359(1):82-9.

Li Z, Yin P, Chen J, Jin S, Liu J, Luo F. CaMKIIa may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway in rats. PLoS One. 2017;12(5).

Pergolizzi Jr JV, Raffa RB, Taylor Jr R, Rodriguez G, Nalamachu S, Langley P. A review of duloxetine 60 mg once-daily dosing for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis pain and low back pain. Pain Pract. 2013;13(3):239-52.

Smith HS, Harris R, Clauw D. Fibromyalgia: an afferent processing disorder leading to a complex pain generalized syndrome. Pain Physician. 2011;14(2):E217-45.

Chappell AS, Ossanna MJ, Liu-Seifert H, Iyengar S, Skljarevski V, Li LC. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial. Pain. 2009;146(3):253-60.

Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: a review. J Clin Pharmacol. 2012;52(1):6-17.

Micó JA, Prieto R. Elucidating the mechanism of action of pregabalin: a(2)d as a therapeutic target in anxiety. CNS Drugs. 2012;26(8):637-48.

Bellato E, Marini E, Castoldi F, Barbasetti N, Mattei L, Bonasia DE. Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment. Pain Res Treat. 2012;2012:426130.

Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(4):1264-73.

Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain. 1996;64(3):493-501.

DuPen A, Shen D, Ersek M. Mechanisms of opioid-induced tolerance and hyperalgesia. Pain Manag Nurs. 2007;8(3):113-21.

Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005;103(1):147-55.

Leal P da C, Clivatti J, Garcia JB, Sakata RK. Opioid-induced hyperalgesia (HIO). Rev Bras Anestesiol. 2010;60(6):639-47.

Mixcoatl-Zecuatl T, Jolivalt CG. A spinal mechanism of action for duloxetine in a rat model of painful diabetic neuropathy. Br J Pharmacol. 2011;164(1):159-69.

Nakajima K, Obata H, Iriuchijima N, Saito S. An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat. Pain. 2012;153(5):990-7.

Andersen J, Stuhr-Hansen N, Zachariassen LG, Koldsø H, Schiøtt B, Strømgaard K. Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (Prozac). Mol Pharmacol. 2014;85(5):703-14.

Iyengar S, Webster AA, Hemrick-Luecke SK, Xu JY, Simmons RM. Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine reuptake inhibitor in persistent pain models in rats. J Pharmacol Exp Ther. 2004;311(2):576-84.

Mixcoatl-Zecuatl T, Jolivalt CG. A spinal mechanism of action for duloxetine in a rat model of painful diabetic neuropathy. Br J Pharmacol. 2011;164(1):159-69.

Obata H. Analgesic mechanisms of antidepressants for neuropathic pain. Int J Mol Sci. 2017;18(11):pii2483.

Cao Y, Wang H, Chiang CY, Dostrovsky JO, Sessle BJ. Pregabalin suppresses nociceptive behavior and central sensitization in a rat trigeminal neuropathic pain model. J Pain. 2013;14(2):193-204.

Submitted date:
03/06/2019

Accepted date:
12/13/2019

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