Evaluation of the nociceptive threshold and inflammatory markers in rats after induction of pulmonary emphysema by elastase in the phasic, inflammatory and neuropathic pain models
Avaliação do limiar nociceptivo e marcadores inflamatórios em ratos após indução de enfisema pulmonar por elastase nos modelos de dor fásica, inflamatória e neuropática
Rafaella Rocha Figueiredo; Isabela de Paula Ribeiro Argôlo; Luiz Fernando Xavier; Josie Resende Silva; Marcelo Lourenço Da-Silva
Abstract
BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction, although it compromises the lungs, it also produces significant systemic consequences. The objective of this study was to analyze the relationship between pro-inflammatory cytokines and nociceptive threshold in rats with porcine pancreatic elastase-induced COPD.
METHODS: 144 animals were randomly distributed into 3 different models: nociceptive phasic pain at tail-flick test (TF), inflammatory pain in the Freund’s complete adjuvant model (CFA) and neuropathic pain in the sciatic nerve constriction model (CCI). 21 days after tracheal instillation of elastase the COPD was established, and the nociceptive threshold was evaluated at different times.
RESULTS: The animals with COPD in TF had a shorter latency time and higher levels of IL-1b, IL-6 and TNF-alpha cytokines. In the CFA and CCI model, the animals with COPD showed an increase in the mechanical hyperalgesia and the levels of IL-1b, IL-6 and TNF-alpha were greater in plasma up to 24 hours.
CONCLUSION: Animals with COPD have higher levels of pro-inflammatory cytokines and reduced nociceptive thresholds, suggesting a relationship between COPD and increased nociception.
Keywords
Resumo
JUSTIFICATIVA E OBJETIVOS: A doença pulmonar obstrutiva crônica (DPOC) caracteriza-se pela obstrução do fluxo aéreo e, embora comprometa os pulmões, produz importantes consequências sistêmicas. O objetivo deste estudo foi analisar a relação entre citocinas pró-inflamatórias e limiar nociceptivo em ratos com DPOC induzida por elastase pancreática suína.
MÉTODOS: Cento e quarenta e quatro animais foram distribuídos aleatoriamente em três modelos diferentes: dor fásica nociceptiva no teste de retirada de cauda (TF), dor inflamatória no modelo de adjuvante completo de Freund (CFA) e dor neuropática no modelo de constrição do nervo ciático (CCI). Vinte e um dias após a instilação traqueal de elastase a DPOC foi estabelecida e o limiar nociceptivo foi avaliado em diferentes períodos.
RESULTADOS: Os animais com DPOC apresentaram menor tempo de latência de retirada e maiores níveis das citocinas IL-1b, IL-6 e TNF-alfa no TF. No modelo CFA e CCI, os animais com DPOC apresentaram aumento da hiperalgesia mecânica e os níveis de IL-1b, IL-6 e TNF-alfa foram maiores no plasma até 24 horas.
CONCLUSÃO: Animais com DPOC apresentam níveis mais elevados de citocinas pró-inflamatórias e limiares nociceptivos reduzidos, sugerindo uma relação entre DPOC e aumento da nocicepção.
Palavras-chave
References
1 Ståhl E, Lindberg A, Jansson SA, Rönmark E, Svensson K, Andersson F, Löfdahl CG, Lundbäck B. Health-related quality of life is related to COPD disease severity. Health Qual Life Outcomes. 2005;3:56.
2 Coelho AEC, Avelar CIS, de Lucena Araujo H, Silva IMP, Mendes LNJ, de Oliveira Bernardino J, Freitas Melo SK, Carneiro Y V, Vasconcelos S T. Abordagem geral da doença pulmonar obstrutiva crônica (DPOC): uma revisão narrativa. Rev Eletr Acervo Médico. 2021;1(1):e8657-e.
3 Couto LC, Melo TA. Efeitos do treinamento resistido na capacidade funcional de pacientes com DPOC hospitalizados: revisão sistemática. Rev Pesqui Fisioter. 2019;9(4):563-71.
4 Monteiro R, Jatene FB, Pazetti R, Correia AT, Manoel LA, Bernardo WM, Rivero DH, Oliveira AS. Avaliação das alterações morfológicas cardíacas secundárias ao enfisema pulmonar: estudo experimental em ratos. Revr Bras Cir Cardiovasc. 2004;19(4):341-7.
5 Roberto J, Brito J, Rogério RJJP. Consenso Brasileiro de Doença Pulmonar Obstrutiva Crônica (DPOC). 2000;26(Supl 1):1.
6 Marques GA, Oliveira PDd, Montzel M, Menezes AMB, Malta DC, Sardinha LMV. Tratamentos utilizados por portadores de DPOC no Brasil: Pesquisa Nacional de Saúde, 2013. 2023;56.
7 Bagatini MA, de Oliveira VdSL, da Silva Naue W, editors. Fisiopatologia do DPOC e suas implicações na funcionalidade. IX Mostra Integrada de Iniciação Científica; 2019.
8 Buss AS, Silva LM. Comparative study of two quality of life questionnaires in patients with COPD. J Bras Pneumol. 2009;35(4):318-24.
9 Eagan TM, Ueland T, Wagner PD, Hardie JA, Mollnes TE, Damås JK, Aukrust P, Bakke PS. Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study. Eur Respir J. 2010;35(3):540-8.
10 Oliveira PC. Apresentações clínicas da DPOC. Pulmão. 2013;22(2):15-8.
11 Junkes-Cunha M, Pelandré G, Maurici RJ. Relationship between levels of inflammatory markers and Sit and Stand activities in individuals with COPD. Braz J Develop, Curitiba. 2021;7(8):80904-16.
12 Part III I. Pain Terms, A Current List with Definitions and Notes on Usage. Classification of Chronic Pain. ed. Seattle: IASP Press; 1994.
13 de Oliveira CM, Sakata RK, Issy AM, Gerola LR, Salomão R. Cytokines and pain. Rev Bras Anestesiol. 2011;61(2):255-65.
14 de Oliveira CMB, Sakata RK, Issy AM, Gerola LR, Salomão RJ. Citocinas e dor. Rev Bras Anestesiol. 2019;61(2):260-5.
15 Chiesa D. Efeito do exercício físico sobre a liberação de interleucina-1 [beta], interleucina-6 e fator de necrose tumoral-[alfa] em homens portadores de doença pulmonar obstrutiva crônica. 2005.
16 Dourado VZ, Tanni SE, Vale SA, Faganello MM, Sanchez F F, Godoy IJ. Manifestações sistêmicas na doença pulmonar obstrutiva crônica. J Bras Pneumol. 2006;32(2):161-71.
17 Minetto M, Rainoldi A, Gazzoni M, Terzolo M, Borrione P, Termine A, Saba L, Dovio A, Angeli A, Paccotti P. Differential responses of serum and salivary interleukin-6 to acute strenuous exercise. Eur J Appl Physiol. 2005;93(5-6):679-86.
18 Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG; NC3Rs Reporting Guidelines Working Group. Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol. 2010;160(7):1577-9.
19 Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16(2):109-10.
20 Cervilha DA. Avaliação experimental da responsividade das vias aéreas em camundongos após indução do enfisema pulmonar por elastase. 2014.
21 Santos LM, de Brito Cervilha DA, Cabral LD, Garcia ÉK, Teixeira V P, Brito JM, Moriya HT, Soncini R. Bronchial responsiveness in an elastase-induced mouse model of emphysema. Respir Physiol Neurobiol. 2014;194:9-14.
22 Azami J, Llewelyn MB, Roberts MHT. The contribution of nucleus reticularis paragigantocellularis and nucleus raphe magnus to the analgesia produced by systemically administered morphine, investigated with the microinjection technique. Pain. 1982;12(3):229-46.
23 Cunha T, Verri Jr W, Poole S, Parada C, Cunha F, Ferreira SJI. Pain facilitation by proinflammatory cytokine actions at peripheral nerve terminals. 2007;67:83.
24 Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33(1):87-107.
25 Farghaly HS, Mahmoud AM, Abdel-Sater KA. Effect of dexmedetomidine and cold stress in a rat model of neuropathic pain: role of interleukin-6 and tumor necrosis factor-a. Eur J Pharmacol. 2016;776:139-45.
26 Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53(1):55-63.
27 Richner M, Bjerrum OJ, Nykjaer A, Vaegter CB. The spared nerve injury (SNI) model of induced mechanical allodynia in mice. J Vis Exp. 2011;18;(54):3092.
28 Akkurt I, Akyıldırım H, Mavi B, Kilincarslan S, Basyigit C. Photon attenuation coefficients of concrete includes barite in different rate. Ann Nucl Energ. 2010;37(7):910-4.
29 Wright JL, Churg A. Smoke-induced emphysema in guinea pigs is associated with morphometric evidence of collagen breakdown and repair. Am J Physiol. 1995;268(1 Pt 1):L17-20.
30 Tolnai J, Szabari M V, Albu G, Maár BA, Parameswaran H, Bartolák-Suki E, Suki B, Hantos Z. Functional and morphological assessment of early impairment of airway function in a rat model of emphysema. J Appl Physiol (1985). 2012;112(11):1932-9.
31 Barnabé V. Efeitos da atividade física intensa e moderada sobre a enfisema pulmonar: Universidade de São Paulo; 2010.
32 Barnes PJ. New concepts in chronic obstructive pulmonary disease. Annu Rev Med. 2003;54:113-29.
33 Antunes MA, Rocco PR. Elastase-induced pulmonary emphysema: insights from experimental models. An Acad Bras Cienc. 2011;83(4):1385-96.
34 Gloeckl R, Schneeberger T, Jarosch I, Kenn K. Pulmonary rehabilitation and exercise training in chronic obstructive pulmonary disease. Dtsch Arztebl Int. 2018;115(8):117-23.
35 Rufino R, Silva JLS. Bases celulares e bioquímicas da doença pulmonar obstrutiva crônica. J Bras Pneumol. 2006;32(3):241-8.
36 David B, Bafadhel M, Koenderman L, De Soyza A. Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait. Torax. 2021;76(2):188-95.
37 Larsson K. Inflammatory markers in COPD. Clin Respir J. 2008;2(Suppl 1):84-7.
38 Mycroft K, Krenke R, Górska K. Eosinophils in COPD-current concepts and clinical implications. J Allergy Clin Immunol Pract. 2020;8(8):2565-74.
39 Woolf CJ, Salter M W. Neuronal plasticity: increasing the gain in pain. Science. 2000;288(5472):1765-9.
40 Millan MJ. Descending control of pain. Progr Neurobil. 2002;66(6):355-474.
41 De Ridder D, Adhia D, Vanneste S. The anatomy of pain and suffering in the brain and its clinical implications. Neurosci Biobehav Rev. 2021;130:125-46.
42 Fonseca JE, Santos MJ, Canhão H, Choy E. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimm Rev. 2009;8(7):538-42.
43 Zaringhalam J, Manaheji H, Mghsoodi N, Farokhi B, Mirzaiee V. Spinal mu-opioid receptor expression and hyperalgesia with dexamethasone in chronic adjuvant-induced arthritis in rats. Clin Exper Phamacol Pysiol. 2008;35(11):1309-15.
44 Julius D. TRP channels and pain. Ann Rev Cell Dev Biol. 2013;29:355-84.
45 Foroud M, Vesal N. Evaluation of the anti-nociceptive effects of morphine, tramadol, meloxicam and their combinations using the tail-flick test in rats. Vet Res Forum. 2015 Fall;6(4):313-8.
46 Farghaly HS, Mahmoud AM, Abdel-Sater KA. Effect of dexmedetomidine and cold stress in a rat model of neuropathic pain: Role of interleukin-6 and tumor necrosis factor-a. Eur J Pharmacol. 2016;776:139-45.
47 Homma Y, Brull SJ, Zhang JM. A comparison of chronic pain behavior following local application of tumor necrosis factor alpha to the normal and mechanically compressed lumbar ganglia in the rat. Pain. 2002;95(3):239-46.
Submitted date:
12/20/2022
Accepted date:
02/24/2023