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Are You Listening? Facilitation of the Auditory Blink Response in People with Fibromyalgia

      Highlights

      • People with fibromyalgia (FM) show greater reactivity to prepulse facilitation than healthy controls do.
      • People with FM show no difference in reactivity to prepulse inhibition than healthy controls do.
      • Activities that decrease autonomic drive may be useful for people with FM.
      • Activities that increase vagal tone may be useful for people with FM.
      • Augmentation of auditory prepulse facilitation may represent a biomarker for FM.

      Abstract

      The purpose of the current study was to determine whether auditory prepulse inhibition (PPI) and/or prepulse facilitation (PPF) were altered in people with fibromyalgia (FM) when compared with controls. Eyeblink responses were recorded from 29 females with FM and 27 controls, while they listened to 3 blocks of auditory stimuli that delivered pulses with either PPI or PPF. Using a linear mixed model, our main findings were that there was a GROUP*CONDITION interaction (F4, 1084 = 4.01, P= .0031) indicating that the difference in amplitude between FM group and control group changed depending on the condition (PPI or PPF). Post hoc tests revealed no differences between the groups in response to PPI. The FM group showed a greater reactivity of response to the PPF conditioned stimulus than the control group did (t(39.7) = 2.03, P= .0494). Augmentation of PPF, as demonstrated by the FM group is thought to be linked to alterations in information processing mediated by an autonomically driven general orienting process. Activities that decrease autonomic drive or rebalance autonomic and parasympathetic tone such as vagal stimulation might be pursued as effective interventions for people with FM.

      Perspective

      This article presents evidence of preservation of neural circuitry that underpins response suppression and evidence of neural circuit disturbance mediated by autonomic drive-in people with FM. These results are important because intact circuitry underpins the effectiveness of therapies and may be harnessed, and rebalancing autonomic drive may be indicated.

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      References

        • Affaitati G
        • Costantini R
        • Tana C
        • Cipollone F
        • Giamberardino MA.
        Co-occurrence of pain syndromes.
        J Neural Transm. 2020; 127: 625-646
        • Andrés-Rodríguez L
        • Borràs X
        • Feliu-Soler A
        • Pérez-Aranda A
        • Rozadilla-Sacanell A
        • Montero-Marin J
        • Maes M
        • Luciano JV.
        Immune-inflammatory pathways and clinical changes in fibromyalgia patients treated with Mindfulness-Based Stress Reduction (MBSR): A randomized, controlled clinical trial.
        Brain Behav Immun. 2019; 80: 109-119
        • Bates D
        • Maechler M
        • Bolker B
        • Walker S.
        Fitting linear mixed-effects models using lme4.
        J Statist Software. 2015; 67: 1-48
        • Bennett R
        • Friend R
        • Jones K
        • Ward R
        • Han B
        • Ross R.
        The revised Fibromyalgia Impact Questionniare (FIQR): Validation and psychometric properties.
        Arthritis Res Ther. 2009; 11: R120
        • Blumenthal T.
        Presidential address 2014: The more-or-less interruptiong effects of the startle response.
        Psychophysiology. 2015; 52: 1417-1431
        • Blumenthal TD
        • Cuthbert BN
        • Filion DL
        • Hackley S
        • Lipp O
        • Von Boxtel A
        Committee report: Guidelines for human startle eyeblink electromyographic studies.
        Psychophysiology. 2005; 42: 1-15
        • Blumenthal TD
        • Elden A
        • Flaten MA.
        A comparison of several methods used to quantify prepulse inhibition of eyeblink responding.
        Psychophysiology. 2004; 41: 326-332
        • Bonaz B
        • Sinniger V
        • Pellissier S.
        Vagus nerve stimulation: A new promising therapeutic tool in inflammatory bowel disease.
        J Intern Med. 2017; 282: 46-63
        • Braff DL
        • Geyer MA
        • Swerdlow NR.
        Human studies of prepulse inhibition of startle: Normal subjects, patient groups, and pharmacological studies.
        Psychopharmacology (Berl). 2001; 156: 234-258
        • Brown TA
        • Chorpita BF
        • Korotitsch W
        • Barlow DH.
        Psychometric properties of the Depression Anxiety Stress Scales (DASS) in clinical samples.
        Behav Res Ther. 1997; 35: 79-89
        • Burckhardt C
        • Clark S
        • Bennett R.
        The fibromyalgia impact questionnaire: Development and validation.
        J Rheumatol. 1991; 18: 728-733
        • Buysse D
        • Reynolds CI
        • Monk T
        • Berman S
        • Kupfer D.
        The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research.
        Psychiatry Res. 1989; 28: 193-213
        • Cagnie B
        • Coppieters I
        • Denecker S
        • Six J
        • Danneels L
        • Meeus M.
        Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI.
        Semin Arthritis Rheum. 2014; 44: 68-75
        • Clauw D.
        Fibromyalgia: A clinical review.
        JAMA. 2014; 31115471555
        • Cohen H
        • Neurmann L
        • Kotler M
        • Buskila D.
        Autonomic nervous system derangement in fibromyalgia syndrome and related disorders.
        Israel Med Assoc J. 2001; 3: 755-760
        • Curran-Everett D.
        Explorations in statistics: The analysis of ratios and normalized data.
        Adv Physiol Educ. 2013; 37: 213-219
        • D'Agnelli S
        • Arendt-Nielsen L
        • Gerra MC
        • Zatorri K
        • Boggiani L
        • Baciarello M
        EB Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers.
        Molecular Pain. 2019; 15: 1-12
        • Desmeules JA
        • Cedraschi C
        • Rapiti E
        • Baumgartner E
        • Finckh A
        • Cohen P
        • Dayer P
        • Vischer TL.
        Neurophysiologic evidence for a central sensitization in patients with fibromyalgia.
        Arthritis Rheum. 2003; 48: 1420-1429
        • Duque L
        • Fricchione G.
        Fibromyalgia and its new lessons for neuropsychiatry.
        Med Sci Monitor Basic Res. 2019; 25: 169-178
        • Edwards RR
        • Dworkin RH
        • Turk DC
        • Angst MS
        • Dionne R
        • Freeman R
        • Hansson P
        • Haroutounian S
        • Arendt-Nielsen L
        • Attal N
        • Baron R
        • Brell J
        • Bujanover S
        • Burke LB
        • Carr D
        • Chappell AS
        • Cowan P
        • Etropolski M
        • Fillingim RB
        • Gewandter JS
        • Katz NP
        • Kopecky EA
        • Markman JD
        • Nomikos G
        • Porter L
        • Rappaport BA
        • Rice AS
        • Scavone JM
        • Scholz J
        • Simon LS
        • Smith SM
        • Tobias J
        • Tockarshewsky T
        • Veasley C
        • Versavel M
        • Wasan AD
        • Wen W
        • Yarnitsky D.
        Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations.
        Pain. 2016; 157: 1851-1871
        • Erdrich S
        • Hawrelak JA
        • Myers SP
        • Harnett JE.
        Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review.
        BMC Musculoskelet Disord. 2020; 21: 181-193
        • Ettinger U
        • Kumari V.
        Effects of sleep deprivation on inhibitory biomarkers of schizophrenia: Implications for drug development.
        The Lancet Psychiatry. 2015; 2: 1028-1035
        • Graham FK.
        The more or less startling effects of weak prestimuli.
        Psychophysiology. 1975; 12: 238-248
        • Harper DE
        • Ichesco E
        • Schrepf A
        • Hampson JP
        • Clauw DJ
        • Schmidt-Wilcke T
        • Harris RE
        • Harte SE.
        Resting functional connectivity of the periaqueductal gray is associated with normal inhibition and pathological facilitation in conditioned pain modulation.
        J Pain. 2018; 19 (635.e631-635.e615)
        • Hauser W
        • Fitzcharles MA.
        Facts and myths pertaining to fibromyalgia.
        Dialogues Clin Neurosci. 2018; 20: 53-62
        • Hseih M
        • Swerdlow N
        • Braff D.
        Effects of background and prepulse characteristics on prepulse inhibition and facilitation: Implications for neuropsychiatric research.
        Biol Psychiatry. 2006; 59: 555-559
        • Ichesco E
        • Puiu T
        • Hampson JP
        • Kairys AE
        • Clauw DJ
        • Harte SE
        • Peltier SJ
        • Harris RE
        • Schmidt-Wilcke T.
        Altered fMRI resting-state connectivity in individuals with fibromyalgia on acute pain stimulation.
        Eur J Pain. 2016; 20: 1079-1089
        • Ichesco E
        • Schmidt-Wilcke T
        • Bhavsar R
        • Clauw DJ
        • Peltier SJ
        • Kim J
        • Napadow V
        • Hampson JP
        • Kairys AE
        • Williams DA
        • Harris RE.
        Altered resting state connectivity of the insular cortex in individuals with fibromyalgia.
        J Pain. 2014; 15: 815-826
        • Ison J
        • McAdam D
        • Hammond G.
        Latency and amplitude changes in the acoustic startle reflex of the rat produced by vartiation in auditory prestimulation.
        Physiol Behav. 1973; 10: 1035-1039
        • Jensen KB
        • Kosek E
        • Petzke F
        • Carville S
        • Fransson P
        • Marcus H
        • Williams SC
        • Choy E
        • Giesecke T
        • Mainguy Y
        • Gracely R
        • Ingvar M.
        Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain.
        Pain. 2009; 144: 95-100
        • Jones KD
        • Mist SD
        • Casselberry MA
        • Ali A
        • Christopher MS
        Fibromyalgia impact and mindfulness characteristics in 4986 people with Fibromyalgia.
        Explore. 2015; 11: 304-309
        • Kishikawa H
        • Matsui T
        • Uchiyama I
        • Miyakawa M
        • Hiramatsu K
        • Stansfeld S.
        The development of Weinstein's noise sensitivity scale.
        Noise Health. 2006; 8: 154-160
        • Kofler M
        • Halder W.
        Alterations in excitatory and inhibitory brainstem interneuronal circuits in fibromyalgia: Evidence of brainstem dysfunction.
        Clin Neurophysiol. 2014; 125: 583-601
        • Kofler M
        • Kumru H
        • Schaller J
        • Saltuari L.
        Blink reflex prepulse inhibition and excitability recovery: Influence of age and sex.
        Clin Neurophysiol. 2013; 124: 126-135
        • Kofler M
        • Muller J
        • Valls-Sole J.
        Auditory startle responses as a probe of brainstem function in healthy subjects and patients with movement disorders.
        Suppl Clin Neurophysiol. 2006; 58: 232-248
        • Kraus T
        • Hosl K
        • Keiss O
        • Schanze A
        • Kornhuber J
        • Forster C.
        BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneaous vagus nerve stimulation.
        J Neural Transm. 2007; 114: 1485-1493
        • Kronmal R.
        Spurious correlation and the fallacy of the ratio standard revisited.
        J Royal Statist Soc Series A (Statistics in Society). 1993; 156: 379-392
        • Lange G
        • Janal MN
        • Maniker A
        • Fitzgibbons J
        • Fobler M
        • Cook D
        • Natelson BH.
        Safety and efficacy of vagus nerve stimulation in fibromyalgia: A phase I/II proof of concept trial.
        Pain Med. 2011; 12: 1406-1413
        • Lee H
        • Lamb SE
        • Bagg MK
        • Toomey E
        • Cashin AG
        • Moseley GL.
        Reproducible and replicable pain research: A critical review.
        Pain. 2018; 159: 1683-1689
        • LETSWAVE
        Version 6. Universite Catholiqu de Louvain.
        Institute of Neuroscience, Belgium2017
        • Lipschitz DS
        • Mayes LM
        • Rasmusson AM
        • Anyan W
        • Billingslea E
        • Gueorguieva R
        • Southwick SM.
        Baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder.
        J Am Acad Child Adolesc Psychiatry. 2005; 44: 807-814
        • Lopez-Sola M
        • Pujol J
        • Wager TD
        • Garcia-Fontanals A
        • Blanco-Hinojo L
        • Garcia-Blanco S
        • Poca-Dias V
        • Harrison BJ
        • Contreras-Rodriguez O
        • Monfort J
        • Garcia-Fructuoso F
        • Deus J.
        Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients.
        Arthritis Rheumatol. 2014; 66: 3200-3209
        • Lovibond S
        • Lovibond P
        Manual for the Depression Anxiety Stress Scales.
        Psychological Foundation, Sydney1995
        • Macfarlane GJ
        • Kronisch C
        • Dean L
        • Atzeni F
        • Hauser W
        • Fluss E
        • Choy E
        • Kosek E
        • Amris K
        • Branco J
        • Dincer F
        • Leino-Arjas P
        • Longley K
        • McCarthy G
        • Makri S
        • Perrot S
        • Sarzi-Puttini P
        • Taylor A
        • Jones G.
        EULAR revised recommendations for the management of fibromyalgia.
        Ann Rheumatic Dis. 2017; 76: 318-328
        • Martinez-Martinez LA
        • Mora T
        • Vargas A
        • Fuentes-Iniestra M
        • Martinez-Lavin M.
        Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: A review of case-control studies.
        J Clin Rheumatol. 2014; 20: 146-150
        • MATLAB
        Version 7.10.0.
        The MathWorks Inc, Natick, Massachusetts2010
        • Mayer T
        • Neblett R
        • Cohen H
        • Howard K
        • Choi Y
        • Williams M
        • Perez Y
        • Gatchel R.
        The development and psychometric validation of the central sensitization inventory.
        Pain Practice. 2012; 12: 276-285
        • Neblett R
        • Cohen H
        • Choi Y
        • Hartzell M
        • Williams M
        • Mayer T
        • Gatchel R.
        The central sensitization inventory (CSI): Establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample.
        J Pain. 2013; 14: 438-445
        • Neuroscan
        Version 4.5 Abbotsford.
        Compumedics, Victoria, Australia2016
        • Paccione CE
        • Diep LM
        • Stubhaug A
        • Jacobsen HB.
        Motivational nondirective resonance breathing versus transcutaneous vagus nerve stimulation in the treatment of fibromyalgia: Study protocol for a randomized controlled trial.
        Trials. 2020; 21: 808-831
        • Petzke F
        • Harris RE
        • Williams DA
        • Clauw DJ
        • Gracely RH.
        Differences in unpleasantness induced by experimental pressure pain between patients with fibromyalgia and healthy controls.
        Eur J Pain. 2005; 9: 325-335
        • Prins A
        • Ouimette P
        • Kimerling R
        • Cameron R
        • Hugelshofer D
        • SHaw-Hegwer J
        • Thrailkill A
        • Gusman F
        • Sheikh J.
        The pimary care PTSD screen (PC-PTSD): Development and operating characteristics.
        Primary Care Psychiatry. 2003; 9: 9-14
        • R Foundation for Statistical Computing
        R Core Team. R: A Language and Environment for Statistical Computing.
        2020 (Vienna, Austria)
        • Randich A
        • Gebhart GF.
        Vagal afferent modulation of nociception.
        Brain Res Rev. 1992; 17: 77-99
        • Salaffi F
        • Sarzi-Puttini P
        • Ciapetti A
        • Atzeni F.
        Clinimetric evaluations of patients with chronic widespread pain.
        Best Pract Res Clin Rheumatol. 2011; 25: 249-270
        • SAS Institute
        SAS/STAT software.
        SAS Institute, Cary, NC2014
        • Scerbo T
        • Colasurdo J
        • Dunn S
        • Unger J
        • Nijs J
        • Cook C.
        Measurement properties of the Central Sensitization Inventory: A systematic review.
        Pain Practice. 2018; 18: 544-554
        • Sullivan M
        • Bishop S
        • Pivik J.
        The pain catastrophizing scale: Development and validation.
        Psychol Assess. 1995; 7: 524-532
        • Swerdlow NR
        • Braff DL
        • Geyer MA.
        Cross-species studies of sensorimotor gating of the startle reflex.
        Ann N Y Acad Sci. 1999; 877: 202-216
        • Swerdlow NR
        • Braff DL
        • Geyer MA.
        Sensorimotor gating of the startle reflex: What we said 25 years ago, what has happened since then, and what comes next.
        J Psychopharmacol. 2016; 30: 1072-1081
        • Swerdlow NR
        • Geyer MA
        • Braff DL.
        Neural circuit regulation of prepulse inhibition of startle in the rat: Current knowledge and future challenges.
        Psychopharmacology (Berl). 2001; 156: 194-215
        • Swerdlow NR
        • Weber M
        • Qu Y
        • Light GA
        • Braff DL.
        Realistic expectations of prepulse inhibition in translational models for schizophrenia research.
        Psychopharmacology (Berl). 2008; 199: 331-388
        • Tang YY
        • Holzel BK
        • Posner MI.
        The neuroscience of mindfulness meditation.
        Nat Rev Neurosci. 2015; 16: 213-225
        • Tiemann L
        • Schulz E
        • Winkelmann A
        • Ronel J
        • Henningsen P
        • Ploner M.
        Behavioral and neuronal investigations of hypervigilance in patients with fibromyalgia syndrome.
        PLoS One. 2012; 7: e35068
        • Torres E
        • Pedersen IN
        • Pérez-Fernández JI.
        Randomized Trial of a Group Music and Imagery Method (GrpMI) for Women with Fibromyalgia.
        J Music Ther. 2018; 55: 186-220
        • Valls-Sole J
        • Valldioriola F
        • Molinuevo J
        • Cossu G
        • Nobbe F.
        Prepulse modulation of the startle reaction and the blink reflex in normal human subjects.
        Exp Brain Res. 1999; 129: 49-56
        • Versace V
        • Campostrini S
        • Sebastianelli L
        • Saltuari L
        • Valls-Sole J
        • Kofler M.
        Influence of posture on blink reflex prepulse inhibition induced by somatosensory inputs from upper and lower limbs.
        Gait Posture. 2019; 73: 120-125
        • Vincent A
        • Lahr BD
        • Wolfe F
        • Clauw DJ
        • Whipple MO
        • Oh TH
        • Barton DL
        • St. Sauver J.
        Prevalence of Fibromyalgia: A population-based study in Olmsted County, Minnesota, utilizing the Rochester Epidemiology Project.
        Arthritis Care Res. 2013; 65: 786-792
        • Vrana SR
        • Calhoun PS
        • McClernon FJ
        • Dennis MF
        • Lee ST
        • Beckham JC.
        Effects of smoking on the acoustic startle response and prepulse inhibition in smokers with and without posttraumatic stress disorder.
        Psychopharmacology (Berl). 2013; 230: 477-485
        • Watson D
        • Clark LA
        • Tellegen A.
        Development and validation of brief measures of positive and negative affect: The PANAS scales.
        J Pers Soc Psychol. 1988; 54: 1063-1070
        • Wolfe F
        • Clauw DJ
        • Fitzcharles MA.
        Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modifiction of the ACR preliminary diagnostic criteria for fibromyalgia.
        J Rheumatol. 2011; 38: 1113-1122
        • Wolfe F
        • Schmukler J
        • Jamal S
        • Castrejon I.
        Diagnosis of Fibromyalgia: Disagreement between fibromyalgia criteria and clinician-based fibromyalgia diagnosis in a university clinic.
        Arthritis Care Res. 2019; 71: 343-351
        • Wynn J
        • Dawson M
        • Schell A
        • McGee M
        • Salveson D
        • Green M.
        Prepulse facilitation and prepulse inhibition in schizophrenia patients and their unaffected siblings.
        Biol Psychiatry. 2004; 55: 518-523