Functional MRI of the Reserpine-Induced Putative Rat Model of Fibromyalgia Reveals Discriminatory Patterns of Functional Augmentation to Acute Nociceptive Stimuli

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jan 13

PMID 28079057

Citations 5

Authors

Jack A Wells

Sayaka Shibata

Akihiko Fujikawa

Masayasu Takahashi

Tsuneo Saga

Ichio Aoki

Affiliations

Soon will be listed here.

Abstract

Functional neuroimaging, applied to pre-clinical models of chronic pain, offers unique advantages in the drive to discover new treatments for this prevalent and oppressive condition. The high spatial and temporal resolution of fMRI affords detailed mapping of regional pharmacodynamics that underlie mechanisms of pain suppression by new analgesics. Despite evidence supporting the translational relevance of this approach, relatively few studies have investigated fMRI abnormalities in rodent models of chronic pain. In this study, we used fMRI to map the BOLD response in a recently developed putative rat model of fibromyalgia to innocuous and acute nociceptive stimuli by applying a step-wise graded electrical forepaw stimulation paradigm, with comparison to healthy controls. We observed discriminatory functional signatures (p < 0.001) to 2 mA electrical forepaw stimulation, found to be innocuous in the control group. As such, this translational approach provides sensitive and quantitative neural correlates of the underlying chronic disease. The regional patterns of functional augmentation were found to be concordant with previous studies of nociception in the anaesthetised rat brain, supporting the specificity of this approach in the study of altered central pain processing in reserpine induced myalgia. The methodology introduced in this work represents a novel platform for emerging treatment evaluation in highly experimentally controlled conditions.

Citing Articles

How does chronic psychosocial distress induce pain? Focus on neuroinflammation and neuroplasticity changes.

Fulop B, Borbely E, Helyes Z Brain Behav Immun Health. 2025; 44:100964.

PMID: 40034488 PMC: 11875130. DOI: 10.1016/j.bbih.2025.100964.

Role of Etanercept and Infliximab on Nociceptive Changes Induced by the Experimental Model of Fibromyalgia.

Cordaro M, Siracusa R, DAmico R, Genovese T, Franco G, Marino Y Int J Mol Sci. 2022; 23(11).

PMID: 35682817 PMC: 9181785. DOI: 10.3390/ijms23116139.

Involvement of Parvalbumin-Positive Neurons in the Development of Hyperalgesia in a Mouse Model of Fibromyalgia.

Miyahara K, Nishimaru H, Matsumoto J, Setogawa T, Taguchi T, Ono T Front Pain Res (Lausanne). 2022; 2:627860.

PMID: 35295447 PMC: 8915639. DOI: 10.3389/fpain.2021.627860.

A candidate neuroimaging biomarker for detection of neurotransmission-related functional alterations and prediction of pharmacological analgesic response in chronic pain.

Martins D, Veronese M, Turkheimer F, Howard M, Williams S, Dipasquale O Brain Commun. 2022; 4(1):fcab302.

PMID: 35169702 PMC: 8833258. DOI: 10.1093/braincomms/fcab302.

Neuroimaging of pain in animal models: a review of recent literature.

Da Silva J, Seminowicz D Pain Rep. 2019; 4(4):e732.

PMID: 31579844 PMC: 6728006. DOI: 10.1097/PR9.0000000000000732.

References

Zhao F, Williams M, Bowlby M, Houghton A, Hargreaves R, Evelhoch J . Qualification of fMRI as a biomarker for pain in anesthetized rats by comparison with behavioral response in conscious rats. Neuroimage. 2013; 84:724-32. DOI: 10.1016/j.neuroimage.2013.09.036. View

Shah Y, Haynes L, Prior M, Marsden C, Morris P, Chapman V . Functional magnetic resonance imaging studies of opioid receptor-mediated modulation of noxious-evoked BOLD contrast in rats. Psychopharmacology (Berl). 2005; 180(4):761-73. DOI: 10.1007/s00213-005-2214-6. View

Johnson A, Myers B, Lazovic J, Towner R, Greenwood-Van Meerveld B . Brain activation in response to visceral stimulation in rats with amygdala implants of corticosterone: an FMRI study. PLoS One. 2010; 5(1):e8573. PMC: 2797306. DOI: 10.1371/journal.pone.0008573. View

Tuor U, Malisza K, Foniok T, Papadimitropoulos R, Jarmasz M, Somorjai R . Functional magnetic resonance imaging in rats subjected to intense electrical and noxious chemical stimulation of the forepaw. Pain. 2000; 87(3):315-324. DOI: 10.1016/S0304-3959(00)00293-1. View

Gracely R, Petzke F, Wolf J, Clauw D . Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002; 46(5):1333-43. DOI: 10.1002/art.10225. View

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; 146(1-2):26-33. DOI: 10.1016/j.pain.2009.05.024. View

Thompson S, Bushnell M . Rodent functional and anatomical imaging of pain. Neurosci Lett. 2012; 520(2):131-9. DOI: 10.1016/j.neulet.2012.03.015. View

Bosshard S, Baltes C, Wyss M, Mueggler T, Weber B, Rudin M . Assessment of brain responses to innocuous and noxious electrical forepaw stimulation in mice using BOLD fMRI. Pain. 2010; 151(3):655-663. DOI: 10.1016/j.pain.2010.08.025. View

Wood P . Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008; 8(5):781-97. DOI: 10.1586/14737175.8.5.781. View

10.

Shih Y, Chen Y, Chen C, Chen J, Chang C, Jaw F . Whole-brain functional magnetic resonance imaging mapping of acute nociceptive responses induced by formalin in rats using atlas registration-based event-related analysis. J Neurosci Res. 2008; 86(8):1801-11. DOI: 10.1002/jnr.21638. View

11.

Giesecke T, Gracely R, Grant M, Nachemson A, Petzke F, Williams D . Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum. 2004; 50(2):613-23. DOI: 10.1002/art.20063. View

12.

Ohashi K, Ichikawa K, Chen L, Callahan M, Zasadny K, Kurebayashi Y . MicroPET detection of regional brain activation induced by colonic distention in a rat model of visceral hypersensitivity. J Vet Med Sci. 2008; 70(1):43-9. DOI: 10.1292/jvms.70.43. View

13.

Schwarz A, Danckaert A, Reese T, Gozzi A, Paxinos G, Watson C . A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI. Neuroimage. 2006; 32(2):538-50. DOI: 10.1016/j.neuroimage.2006.04.214. View

14.

Hess A, Sergejeva M, Budinsky L, Zeilhofer H, Brune K . Imaging of hyperalgesia in rats by functional MRI. Eur J Pain. 2006; 11(1):109-19. DOI: 10.1016/j.ejpain.2006.01.005. View

15.

Sluka K . Is it possible to develop an animal model of fibromyalgia?. Pain. 2009; 146(1-2):3-4. PMC: 2760666. DOI: 10.1016/j.pain.2009.07.032. View

16.

Clauw D, Crofford L . Chronic widespread pain and fibromyalgia: what we know, and what we need to know. Best Pract Res Clin Rheumatol. 2003; 17(4):685-701. DOI: 10.1016/s1521-6942(03)00035-4. View

17.

Zhao F, Welsh D, Williams M, Coimbra A, Urban M, Hargreaves R . fMRI of pain processing in the brain: a within-animal comparative study of BOLD vs. CBV and noxious electrical vs. noxious mechanical stimulation in rat. Neuroimage. 2011; 59(2):1168-79. DOI: 10.1016/j.neuroimage.2011.08.002. View

18.

Borchers A, Gershwin M . Fibromyalgia: A Critical and Comprehensive Review. Clin Rev Allergy Immunol. 2015; 49(2):100-51. DOI: 10.1007/s12016-015-8509-4. View

19.

Malisza K, Gregorash L, Turner A, Foniok T, Stroman P, Allman A . Functional MRI involving painful stimulation of the ankle and the effect of physiotherapy joint mobilization. Magn Reson Imaging. 2003; 21(5):489-96. DOI: 10.1016/s0730-725x(03)00074-2. View

20.

Schrepf A, Harper D, Harte S, Wang H, Ichesco E, Hampson J . Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study. Pain. 2016; 157(10):2217-2225. PMC: 5028286. DOI: 10.1097/j.pain.0000000000000633. View