Advertisement

Pain, Fatigue, and Cognitive Symptoms Are Temporally Associated Within but Not Across Days in Multiple Sclerosis

      Abstract

      Objective

      To examine the temporal associations, within day and day to day, between pain, fatigue, depressed mood, and cognitive function in multiple sclerosis (MS).

      Design

      Repeated-measures study involving 7 days of ecological momentary assessment (EMA) of symptoms 5 times a day; multilevel mixed models were used to analyze data.

      Setting

      Community.

      Participants

      Ambulatory adults (N=107) with MS.

      Interventions

      Not applicable.

      Main Outcome Measure

      EMA of pain, fatigue, depressed mood, and cognitive function rated on a 0 to 10 scale.

      Results

      Fatigue and pain were linked within day such that higher pain was associated with higher subsequent fatigue (B=.09, P=.04); likewise, higher fatigue was associated with higher pain in the following time frame (B=.05, P=.04). Poorer perceived cognitive function preceded increased subsequent pain (B=.08, P=.007) and fatigue (B=.10, P=.01) within day. Depressed mood was not temporally linked with other symptoms. In terms of day-to-day effects, a day of higher fatigue related to decreased next day fatigue (B=−.16, P=.01), and a day of higher depressed mood related to increased depressed mood the next day (B=.17, P=.01). There were no cross-symptom associations from one day to the next.

      Conclusions

      Findings provide new insights on how common symptoms in MS relate to each other and vary within and over days. Pain and fatigue show evidence of a dynamic bidirectional relation over the course of a day, and worsening of perceived cognitive function preceded worsening of both pain and fatigue. Most temporal associations between symptoms occur within the course of a day, with relatively little carryover from one day to the next.

      Keywords

      List of abbreviations:

      EMA (ecological momentary assessment), MS (multiple sclerosis)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Archives of Physical Medicine and Rehabilitation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hauser S.L.
        • Oksenberg J.R.
        The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration.
        Neuron. 2006; 52: 61-76
        • Noseworthy J.H.
        Progress in determining the causes and treatment of multiple sclerosis.
        Nature. 1999; 399: A40-A47
        • Noseworthy J.H.
        • Lucchinetti C.
        • Rodriguez M.
        • Weinshenker B.G.
        Multiple sclerosis.
        N Engl J Med. 2000; 343: 938-952
        • Ehde D.M.
        • Gibbons L.E.
        • Chwastiak L.
        • Bombardier C.H.
        • Sullivan M.D.
        • Kraft G.H.
        Chronic pain in a large community sample of persons with multiple sclerosis.
        Mult Scler. 2003; 9: 605-611
        • Ehde D.M.
        • Osborne T.L.
        • Hanley M.A.
        • Jensen M.P.
        • Kraft G.H.
        The scope and nature of pain in persons with multiple sclerosis.
        Mult Scler. 2006; 12: 629-638
        • Ehde D.M.
        • Osborne T.L.
        • Jensen M.P.
        Chronic pain in persons with multiple sclerosis.
        Phys Med Rehabil Clin N Am. 2005; 16: 503-512
        • Hirsh A.T.
        • Turner A.P.
        • Ehde D.M.
        • Haselkorn J.K.
        Prevalence and impact of pain in multiple sclerosis: physical and psychologic contributors.
        Arch Phys Med Rehabil. 2009; 90: 646-651
        • Kos D.
        • Kerckhofs E.
        • Nagels G.
        • D'Hooghe M.B.
        • Ilsbroukx S.
        Origin of fatigue in multiple sclerosis: review of the literature.
        Neurorehabil Neural Repair. 2008; 22: 91-100
        • Krupp L.B.
        Fatigue in multiple sclerosis: definition, pathophysiology and treatment.
        CNS Drugs. 2003; 17: 225-234
        • Krupp L.B.
        • Alvarez L.A.
        • LaRocca N.G.
        • Scheinberg L.C.
        Fatigue in multiple sclerosis.
        Arch Neurol. 1988; 45: 435-437
        • Krupp L.B.
        • Christodoulou C.
        Fatigue in multiple sclerosis.
        Curr Neurol Neurosci Rep. 2001; 1: 294-298
        • Krupp L.B.
        • Serafin D.J.
        • Christodoulou C.
        Multiple sclerosis-associated fatigue.
        Expert Rev Neurother. 2010; 10: 1437-1447
        • MacAllister W.S.
        • Krupp L.B.
        Multiple sclerosis-related fatigue.
        Phys Med Rehabil Clin N Am. 2005; 16: 483-502
        • Joy J.E.
        • Johnston R.B.
        Multiple sclerosis: current status and strategies for the future.
        National Academies Press, The National Academies, Washington, D.C.2001
        • Hadjimichael O.
        • Kerns R.D.
        • Rizzo M.A.
        • Cutter G.
        • Vollmer T.
        Persistent pain and uncomfortable sensations in persons with multiple sclerosis.
        Pain. 2007; 127: 35-41
        • Khan F.
        • Pallant J.
        Chronic pain in multiple sclerosis: prevalence, characteristics, and impact on quality of life in an Australian community cohort.
        J Pain. 2007; 8: 614-623
        • Amato M.P.
        • Ponziani G.
        • Siracusa G.
        • Sorbi S.
        Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years.
        Arch Neurol. 2001; 58: 1602-1606
        • Bagert B.
        • Camplair P.
        • Bourdette D.
        Cognitive dysfunction in multiple sclerosis: natural history, pathophysiology and management.
        CNS Drugs. 2002; 16: 445-455
        • Chiaravalloti N.D.
        • DeLuca J.
        Cognitive impairment in multiple sclerosis.
        Lancet Neurol. 2008; 7: 1139-1151
        • Huijbregts S.C.
        • Kalkers N.F.
        • de Sonneville L.M.
        • de Groot V.
        • Reuling I.E.
        • Polman C.H.
        Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS.
        Neurology. 2004; 63: 335-339
        • Kesselring J.
        • Klement U.
        Cognitive and affective disturbances in multiple sclerosis.
        J Neurol. 2001; 248: 180-183
        • Lazeron R.H.
        • Boringa J.B.
        • Schouten M.
        • et al.
        Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis.
        Mult Scler. 2005; 11: 524-531
        • Motl R.W.
        • McAuley E.
        Symptom cluster as a predictor of physical activity in multiple sclerosis: preliminary evidence.
        J Pain Symptom Manage. 2009; 38: 270-280
        • Motl R.W.
        • Weikert M.
        • Suh Y.
        • Dlugonski D.
        Symptom cluster and physical activity in relapsing-remitting multiple sclerosis.
        Res Nurs Health. 2010; 33: 398-412
        • Kraft G.H.
        • Johnson K.L.
        • Yorkston K.
        • et al.
        Setting the agenda for multiple sclerosis rehabilitation research.
        Mult Scler. 2008; 14: 1292-1297
        • Alschuler K.N.
        • Ehde D.M.
        • Jensen M.P.
        The co-occurrence of pain and depression in adults with multiple sclerosis.
        Rehabil Psychol. 2013; 58: 217-221
        • Alschuler K.N.
        • Ehde D.M.
        • Jensen M.P.
        Co-occurring depression and pain in multiple sclerosis.
        Phys Med Rehabil Clin N Am. 2013; 24: 703-715
        • Amtmann D.
        • Askew R.L.
        • Kim J.
        • et al.
        Pain affects depression through anxiety, fatigue, and sleep in multiple sclerosis.
        Rehabil Psychol. 2015; 60: 81-90
        • McAuley E.
        • White S.M.
        • Rogers L.Q.
        • Motl R.W.
        • Courneya K.S.
        Physical activity and fatigue in breast cancer and multiple sclerosis: psychosocial mechanisms.
        Psychosom Med. 2010; 72: 88-96
        • Motl R.W.
        • McAuley E.
        • Wynn D.
        • Suh Y.
        • Weikert M.
        • Dlugonski D.
        Symptoms and physical activity among adults with relapsing-remitting multiple sclerosis.
        J Nerv Ment Dis. 2010; 198: 213-219
        • Heine M.
        • van den Akker L.E.
        • Blikman L.
        • et al.
        Real-time assessment of fatigue in patients with multiple sclerosis: how does it relate to commonly used self-report fatigue questionnaires?.
        Arch Phys Med Rehabil. 2016; 97: 1887-1894
        • Kim E.
        • Lovera J.
        • Schaben L.
        • Melara J.
        • Bourdette D.
        • Whitham R.
        Novel method for measurement of fatigue in multiple sclerosis: real-time digital fatigue score.
        J Rehabil Res Dev. 2010; 47: 477-484
        • Powell D.J.
        • Liossi C.
        • Schlotz W.
        • Moss-Morris R.
        Tracking daily fatigue fluctuations in multiple sclerosis: ecological momentary assessment provides unique insights.
        J Behav Med. 2017 Mar 9; ([Epub ahead of print])
        • Kratz A.L.
        • Murphy S.L.
        • Braley T.J.
        Ecological momentary assessment of pain, fatigue, depressive, and cognitive symptoms reveals significant daily variability in multiple sclerosis.
        Arch Phys Med Rehabil. 2017; 98: 2142-2150
        • Kratz A.L.
        • Braley T.J.
        • Foxen-Craft E.
        • Scott E.
        • Murphy 3rd, J.F.
        • Murphy S.L.
        How do pain, fatigue, depressive, and cognitive symptoms relate to well-being and social and physical functioning in the daily lives of individuals with multiple sclerosis?.
        Arch Phys Med Rehabil. 2017; 98: 2160-2166
        • Enders C.K.
        • Tofighi D.
        Centering predictor variables in cross-sectional multilevel models: a new look at an old issue.
        Psychol Methods. 2007; 12: 121-138
        • Enders C.K.
        Centering predictors and contextual effects.
        in: Scott M.A. Simonoff J.S. Marx B.D. The SAGE handbook of multilevel modeling. Sage Publications, Thousand Oaks2013: 89-107
        • Cohen J.
        • Cohen P.
        • West S.G.
        • Aiken L.S.
        Applied multiple regression/correlation analyses for the behavioral sciences.
        3rd ed. Lawrence Erlbaum Associates, Mahwah2003
        • Singer J.D.
        • Willett J.B.
        Applied longitudinal data analysis: modeling change and event occurrence.
        Oxford University Press, New York2003
        • Bushnell M.C.
        • Ceko M.
        • Low L.A.
        Cognitive and emotional control of pain and its disruption in chronic pain. Nature reviews.
        Neuroscience. 2013; 14: 502-511
        • Lorenz J.
        • Bromm B.
        Event-related potential correlates of interference between cognitive performance and tonic experimental pain.
        Psychophysiology. 1997; 34: 436-445
        • Lorenz J.
        • Beck H.
        • Bromm B.
        Cognitive performance, mood and experimental pain before and during morphine-induced analgesia in patients with chronic non-malignant pain.
        Pain. 1997; 73: 369-375
        • Eccleston C.
        • Crombez G.
        Pain demands attention: a cognitive-affective model of the interruptive function of pain.
        Psychol Bull. 1999; 125: 356-366
        • Remy F.
        • Frankenstein U.N.
        • Mincic A.
        • Tomanek B.
        • Stroman P.W.
        Pain modulates cerebral activity during cognitive performance.
        Neuroimage. 2003; 19: 655-664
        • Seminowicz D.A.
        • Davis K.D.
        Pain enhances functional connectivity of a brain network evoked by performance of a cognitive task.
        J Neurophysiol. 2007; 97: 3651-3659
        • Erpelding N.
        • Davis K.D.
        Neural underpinnings of behavioural strategies that prioritize either cognitive task performance or pain.
        Pain. 2013; 154: 2060-2071
        • Kratz A.L.
        • Schepens S.L.
        • Murphy S.L.
        Effects of cognitive task demands on subsequent symptoms and activity in adults with symptomatic osteoarthritis.
        Am J Occup Ther. 2013; 67: 683-691
        • O'Connor A.B.
        • Schwid S.R.
        • Herrmann D.N.
        • Markman J.D.
        • Dworkin R.H.
        Pain associated with multiple sclerosis: systematic review and proposed classification.
        Pain. 2008; 137: 96-111
        • Arnett P.A.
        • Barwick F.H.
        • Beeney J.E.
        Depression in multiple sclerosis: review and theoretical proposal.
        J Int Neuropsych Soc. 2008; 14: 691-724
        • Braley T.J.
        • Segal B.M.
        • Chervin R.D.
        Obstructive sleep apnea and fatigue in patients with multiple sclerosis.
        J Clin Sleep Med. 2014; 10: 155-162
        • Krupp L.B.
        • LaRocca N.G.
        • Muir-Nash J.
        • Steinberg A.D.
        The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.
        Arch Neurol. 1989; 46: 1121-1123
        • Amtmann D.
        • Bamer A.M.
        • Johnson K.L.
        • et al.
        A comparison of multiple patient reported outcome measures in identifying major depressive disorder in people with multiple sclerosis.
        J Psychosom Res. 2015; 79: 550-557
        • Stone A.A.
        • Shiffman S.
        Ecological momentary assessment (EMA) in behavioral medicine.
        Ann Behav Med. 1994; 16: 199-202
        • Abelson R.P.
        A variance explanation paradox: when a little is a lot.
        Psychol Bull. 1985; 97: 129-133
        • Cohen J.
        Statistical power analyses for the behavioral sciences.
        Lawrence Erlbaum Associates, Hillsdale1987