Skip to main content
SearchLoginLogin or Signup

Kinin B1 receptor is involved in mechanical nociception in a fibromyalgia-like model in mice

Published onNov 24, 2020
Kinin B1 receptor is involved in mechanical nociception in a fibromyalgia-like model in mice


Fibromyalgia-like models in mice induced by reserpine have opened a new avenue to understanding the molecular mechanisms behind this complex and incapacitating pain syndrome. The kinin B1 receptor (B1R) contributes to mechanical allodynia and acute coping behavior in mice with inflammatory and immunological disorders. This study has replicated previous data where amine depletion induced by reserpine significantly decreased the dopamine and serotonin levels in the prefrontal cortex (PFC), hippocampus (HPC), and spinal cord of mice. The animals subjected to the reserpine fibromyalgia model also showed decreased paw withdrawal threshold (PWT) and increased the immobility time in the forced swimming test (FST). Genetic ablation of B1R or pharmacological blockade by selective kinin B1R antagonist R-715 (acute i.p. treatment) counteracted the mechanical allodynia and increased immobility time induced by reserpine. However, neither pharmacological nor genetic inhibition of B1R reversed monoamine depletion. Our data confirm that reserpine induced a fibromyalgia-like phenotype in mice and reiterated the role of B1R on acute coping behavior and nociception modulation.

Keywords: fibromyalgia, reserpine, kinin, B1 receptor, pregabalin


Reviewer’s Comments


Wolfe F, Schmukler J, Jamal S, Castrejon I, Gibson KA, Srinivasan S, et al. Diagnosis of Fibromyalgia: Disagreement Between Fibromyalgia Criteria and Clinician-Based Fibromyalgia Diagnosis in a University Clinic. Arthritis Care Res (Hoboken). 2019 Mar;71(3):343–51.

Galvez-Sánchez CM, Reyes Del Paso GA. Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives. J Clin Med. 2020 Apr 23;9(4).

Arnold LM, Gebke KB, Choy EHS. Fibromyalgia: management strategies for primary care providers. Int J Clin Pract. 2016 Feb;70(2):99–112.

Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res ( Hoboken). 2010 May;62(5):600–10.

Smith HS, Harris R, Clauw D. Fibromyalgia: an afferent processing disorder leading to a complex pain generalized syndrome. Pain Physician. 2011 Apr;14(2):E217-245.

Jensen KB, Loitoile R, Kosek E, Petzke F, Carville S, Fransson P, et al. Patients with fibromyalgia display less functional connectivity in the brain’s pain inhibitory network. Mol Pain. 2012 Apr 26;8:32.

Tzadok R, Ablin JN. Current and Emerging Pharmacotherapy for Fibromyalgia. Pain Res Manag. 2020;2020:6541798.

Mease PJ, Dundon K, Sarzi-Puttini P. Pharmacotherapy of fibromyalgia. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):285–97.

Taguchi T, Katanosaka K, Yasui M, Hayashi K, Yamashita M, Wakatsuki K, et al. Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model: PAIN. 2015 Mar;156(3):415–27.

Cheung M, Parmar M. Reserpine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 [cited 2020 Sep 11]. Available from:

Klein CP, Sperotto NDM, Maciel IS, Leite CE, Souza AH, Campos MM. Effects of D-series resolvins on behavioral and neurochemical changes in a fibromyalgia-like model in mice. Neuropharmacology. 2014 Nov;86:57–66.

Brusco I, Justino AB, Silva CR, Fischer S, Cunha TM, Scussel R, et al. Kinins and their B1 and B2 receptors are involved in fibromyalgia-like pain symptoms in mice. Biochem Pharmacol. 2019 Jun 26;168:119–32.

Viana AF, Maciel IS, Dornelles FN, Figueiredo CP, Siqueira JM, Campos MM, et al. Kinin B1 receptors mediate depression-like behavior response in stressed mice treated with systemic E. coli lipopolysaccharide. J Neuroinflammation. 2010 Dec 31;7:98.

de Souza Maciel I, Azevedo VM, Oliboni P, Campos MM. Blockade of Kinin B 1 receptor counteracts the depressive-like behavior and mechanical allodynia in ovariectomized mice [Internet]. Animal Behavior and Cognition; 2020 Sep [cited 2020 Sep 11]. Available from:

Nagakura Y, Oe T, Aoki T, Matsuoka N. Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia. Pain. 2009 Nov;146(1–2):26–33.

Dagnino APA, da Silva RBM, Chagastelles PC, Pereira TCB, Venturin GT, Greggio S, et al. Nociceptin/orphanin FQ receptor modulates painful and fatigue symptoms in a mouse model of fibromyalgia. Pain. 2019;160(6):1383–401.

Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994 Jul;53(1):55–63.

Dixon WJ. Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol. 1980;20:441–62.

Maciel IS, Silva RBM, Morrone FB, Calixto JB, Campos MM. Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice. PLoS ONE. 2013;8(9):e77227.

Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol. 1978 Feb 15;47(4):379–91.

Costa R, Motta EM, Dutra RC, Manjavachi MN, Bento AF, Malinsky FR, et al. Anti-nociceptive effect of kinin B₁ and B₂ receptor antagonists on peripheral neuropathy induced by paclitaxel in mice. Br J Pharmacol. 2011 Sep;164(2b):681–93.

González RR, Fernández RF, Vidal JLM, Frenich AG, Pérez MLG. Development and validation of an ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) method for the simultaneous determination of neurotransmitters in rat brain samples. J Neurosci Methods. 2011 Jun 15;198(2):187–94.

Veselinović T, Schorn H, Vernaleken I, Schiffl K, Hiemke C, Zernig G, et al. Effects of antipsychotic treatment on psychopathology and motor symptoms. A placebo-controlled study in healthy volunteers. Psychopharmacology (Berl). 2011 Dec;218(4):733–48.

Yao X, Li L, Kandhare AD, Mukherjee-Kandhare AA, Bodhankar SL. Attenuation of reserpine-induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol. Exp Ther Med. 2020 Feb;19(2):1343–55.

Peres Klein C, Rodrigues Cintra M, Binda N, Montijo Diniz D, Gomez MV, Souto AA, et al. Coadministration of Resveratrol and Rice Oil Mitigates Nociception and Oxidative State in a Mouse Fibromyalgia-Like Model. Pain Res Treat. 2016;2016:3191638.

Singh L, Kaur A, Garg S, Singh AP, Bhatti R. Protective Effect of Esculetin, Natural Coumarin in Mice Model of Fibromyalgia: Targeting Pro-Inflammatory Cytokines and MAO-A. Neurochem Res [Internet]. 2020 Jul 16 [cited 2020 Sep 11]; Available from:

Blasco-Serra A, Escrihuela-Vidal F, González-Soler EM, Martínez-Expósito F, Blasco-Ausina MC, Martínez-Bellver S, et al. Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats. Physiology & Behavior. 2015 Nov;151:456–62.

Molendijk ML, de Kloet ER. Immobility in the forced swim test is adaptive and does not reflect depression. Psychoneuroendocrinology. 2015 Dec;62:389–91.

Commons KG, Cholanians AB, Babb JA, Ehlinger DG. The Rodent Forced Swim Test Measures Stress-Coping Strategy, Not Depression-like Behavior. ACS Chem Neurosci. 2017 17;8(5):955–60.

Bogdanova OV, Kanekar S, D’Anci KE, Renshaw PF. Factors influencing behavior in the forced swim test. Physiol Behav. 2013 Jun 13;118:227–39.

Ahmed-Farid O, Ahmed R, Saleh D. Combination of resveratrol and fluoxetine in an acute model of depression in mice: Prevention of oxidative DNA fragmentation and monoamines degradation. J App Pharm Sci. 2016;001–7.

Skalisz L. Evaluation of the face validity of reserpine administration as an animal model of depression–Parkinson’s disease association. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2002 Jun;26(5):879–83.

No comments here
Why not start the discussion?