Skip to main content
SpringerLink
Log in

Pain and Cognition in Multiple Sclerosis

  • Chapter
  • First Online:
Behavioral Neurobiology of Chronic Pain

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 20))

Abstract

There is a high prevalence of pain, depression, and cognitive dysfunction in patients with Multiple Sclerosis (MS). These symptoms affect daily tasks resulting in a significant reduction in quality of life. Pain and cognitive changes have been studied across various animal models of MS. In these models the onset of pain and cognitive dysfunction occur early, and do not coincide with the pattern of motor deficits. This is likely underpinned by a number of different mechanisms including changes in glutamate transmission, glial cell activation, and increased levels of pro-inflammatory cytokines. Changes in pain and cognition have been described as belonging to a cluster of symptoms and have been linked through centrally driven processes. In particular, the overactive immune response can induce a state of “sickness-like behaviours” that can influence both pain and cognition. Investigating the mechanism of inflammatory sickness behaviors in MS could lead to a better understanding of the links between pain and cognition. There are currently few effective treatments for pain and cognition dysfunction in MS. Studying the relationship between these symptoms will allow better management of both symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abhinav K et al (2012) Clinicopathological review of patients with and without multiple sclerosis treated by partial sensory rhizotomy for medically refractory trigeminal neuralgia: a 12-year retrospective study. Clin Neurol Neurosurg 114:361–365

    Article  PubMed  Google Scholar 

  • Aicher SA et al (2004) Hyperalgesia in an animal model of multiple sclerosis. Pain 110:560–570

    Article  CAS  PubMed  Google Scholar 

  • Al-Araji AH, Oger J (2005) Reappraisal of Lhermitte’s sign in multiple sclerosis. Mult Scler 11:398–402

    Article  PubMed  Google Scholar 

  • Amato MP et al (2010) Relevance of cognitive deterioration in early relapsing-remitting MS: a 3-year follow-up study. Mult Scler 16:1474–1482

    Article  PubMed  Google Scholar 

  • Archibald CJ et al (1994) Pain prevalence, severity and impact in a clinic sample of multiple sclerosis patients. Pain 58:89–93

    Article  CAS  PubMed  Google Scholar 

  • Beggs S et al (2012) P2X4R + microglia drive neuropathic pain. Nat Neurosci 15:1068–1073

    Article  CAS  PubMed  Google Scholar 

  • Beiske AG et al (2009) Pain in Parkinson’s disease: prevalence and characteristics. Pain 141:173–177

    Article  CAS  PubMed  Google Scholar 

  • Berard JL et al (2010) Characterization of relapsing-remitting and chronic forms of experimental autoimmune encephalomyelitis in C57BL/6 mice. Glia 58:434–445

    Article  PubMed  Google Scholar 

  • Bergendal G et al (2007) Selective decline in information processing in subgroups of multiple sclerosis: an 8-year longitudinal study. Eur Neurol 57:193–202

    Article  CAS  PubMed  Google Scholar 

  • Blank T, Prinz M (2013) Microglia as modulators of cognition and neuropsychiatric disorders. Glia 61:62–70

    Article  PubMed  Google Scholar 

  • Butler MA et al (2009) How the conflict between American psychiatry and neurology delayed the appreciation of cognitive dysfunction in multiple sclerosis. Neuropsychol Rev 19:399–410

    Article  PubMed  Google Scholar 

  • Calabrese M et al (2009) Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 66:1144–1150

    Article  PubMed  Google Scholar 

  • Chwastiak L et al (2002) Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample. Am J Psychiatry 159:1862–1868

    Article  PubMed  Google Scholar 

  • Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231

    Article  PubMed  Google Scholar 

  • Cruccu G et al (2009) Trigeminal neuralgia and pain related to multiple sclerosis. Pain 143:186–191

    Article  CAS  PubMed  Google Scholar 

  • D’Intino G et al (2005) Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats. Proc Natl Acad Sci USA 102:3070–3075

    Article  PubMed Central  PubMed  Google Scholar 

  • Dantzer R (2001) Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 933:222–234

    Article  CAS  PubMed  Google Scholar 

  • David S, Kroner A (2011) Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 12:388–399

    Article  CAS  PubMed  Google Scholar 

  • DeLuca J et al (1998) Acquisition and storage deficits in multiple sclerosis. J Clin Exp Neuropsychol 20:376–390

    Article  CAS  PubMed  Google Scholar 

  • Demaree HA et al (2000) Learning impairment is associated with recall ability in multiple sclerosis. J Clin Exp Neuropsychol 22:865–873

    Article  CAS  PubMed  Google Scholar 

  • Denney DR et al (2008) A 3-year longitudinal study of cognitive impairment in patients with primary progressive multiple sclerosis: speed matters. J Neurol Sci 267:129–136

    Article  PubMed  Google Scholar 

  • Dutra RC et al (2013a) The role of kinin B1 and B2 receptors in the persistent pain induced by experimental autoimmune encephalomyelitis (EAE) in mice: evidence for the involvement of astrocytes. Neurobiol Dis 54:82–93

    Article  CAS  PubMed  Google Scholar 

  • Dutra RC, Moreira EL, Alberti TB, Marcon R, Prediger RD, Calixto JB (2013b) Spatial reference memory deficits precede motor dysfunction in an experimental autoimmune encephalomyelitis model: the role of kallikrein-kinin system. Brain Behav Immun 33:90–101

    Google Scholar 

  • Feinstein A (2011) Multiple sclerosis and depression. Mult Scler 17:1276–1281

    Article  PubMed  Google Scholar 

  • Feinstein A et al (2004) Structural brain abnormalities in multiple sclerosis patients with major depression. Neurology 62:586–590

    Article  CAS  PubMed  Google Scholar 

  • Fletcher JM et al (2010) T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 162:1–11

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Foley PL et al (2013) Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis. Pain 154:632–642

    Article  PubMed  Google Scholar 

  • Friese MA, Fugger L (2009) Pathogenic CD8(+) T cells in multiple sclerosis. Ann Neurol 66:132–141

    Article  CAS  PubMed  Google Scholar 

  • Genova HM et al (2012) Processing speed versus working memory: contributions to an information-processing task in multiple sclerosis. Appl Neuropsychol Adult 19:132–140

    Article  PubMed Central  PubMed  Google Scholar 

  • Gold SM, O’Connor MF, Gill R, Kern KC, Shi Y, Henry RG et al (2014) Detection of altered hippocampal morphology in multiple sclerosis-associated depression using automated surface mesh modeling. Hum Brain Mapp 35:30–37

    Google Scholar 

  • Grasso MG et al (2008) Pain in multiple sclerosis: a clinical and instrumental approach. Mult Scler 14:506–513

    Article  CAS  PubMed  Google Scholar 

  • Guimaraes J, Sa MJ (2012) Cognitive dysfunction in multiple sclerosis. Front Neurol 3:74

    Article  PubMed Central  PubMed  Google Scholar 

  • Haji N et al (2012) TNF-alpha-mediated anxiety in a mouse model of multiple sclerosis. Exp Neurol 237:296–303

    Article  CAS  PubMed  Google Scholar 

  • Hart RP et al (2000) Chronic pain and neuropsychological functioning. Neuropsychol Rev 10:131–149

    Article  CAS  PubMed  Google Scholar 

  • Hauser SL and Oksenberg JR (2006) The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52:61–76

    Google Scholar 

  • Heesen C et al (2006) Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour? J Neurol Neurosurg Psychiatry 77:34–39

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hirsh AT et al (2009) Prevalence and impact of pain in multiple sclerosis: physical and psychologic contributors. Arch Phys Med Rehabil 90:646–651

    Article  PubMed Central  PubMed  Google Scholar 

  • Huizinga R et al (2012) Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis. Glia 60:422–431

    Article  PubMed  Google Scholar 

  • Ji RR, Berta T, Nedergaard M et al (2013) Glia and pain: is chronic pain a gliopathy? Pain 154(Suppl 1):S10–S28

    Google Scholar 

  • Julian LJ (2011) Cognitive functioning in multiple sclerosis. Neurol Clin 29:507–525

    Article  PubMed  Google Scholar 

  • Kelley KW et al (2003) Cytokine-induced sickness behavior. Brain Behav Immun 17(Suppl 1):S112–S118

    Article  CAS  PubMed  Google Scholar 

  • Kim K et al (2011) Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol 226:2484–2493

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Krumbholz M et al (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 8:613–623

    Article  CAS  PubMed  Google Scholar 

  • Langdon DW (2011) Cognition in multiple sclerosis. Curr Opin Neurol 24:244–249

    Article  PubMed  Google Scholar 

  • Lester K et al (2007) The association of illness severity, self-reported cognitive impairment, and perceived illness management with depression and anxiety in a multiple sclerosis clinic population. J Behav Med 30:177–186

    Article  PubMed  Google Scholar 

  • Love S, Coakham HB (2001) Trigeminal neuralgia: pathology and pathogenesis. Brain 124:2347–2360

    Article  CAS  PubMed  Google Scholar 

  • Love S et al (2001) Trigeminal neuralgia due to multiple sclerosis: ultrastructural findings in trigeminal rhizotomy specimens. Neuropathol Appl Neurobiol 27:238–244

    Article  CAS  PubMed  Google Scholar 

  • Low LA (2013) The impact of pain upon cognition: what have rodent studies told us? Pain 154:2603–2605

    Google Scholar 

  • Lynch JL et al (2008) Analysis of nociception, sex and peripheral nerve innervation in the TMEV animal model of multiple sclerosis. Pain 136:293–304

    Article  PubMed Central  PubMed  Google Scholar 

  • Maloni HW (2000) Pain in multiple sclerosis: an overview of its nature and management. J Neurosci Nurs 32(139–44):152

    Google Scholar 

  • Maurelli M et al (1992) Neuropsychological assessment in MS: clinical, neurophysiological and neuroradiological relationships. Acta Neurol Scand 86:124–128

    Article  CAS  PubMed  Google Scholar 

  • Mayo L et al (2012) The innate immune system in demyelinating disease. Immunol Rev 248:170–187

    Article  PubMed Central  PubMed  Google Scholar 

  • Moriarty O et al (2011) The effect of pain on cognitive function: a review of clinical and preclinical research. Prog Neurobiol 93:385–404

    Article  PubMed  Google Scholar 

  • Motl RW et al (2010a) Symptoms and physical activity among adults with relapsing-remitting multiple sclerosis. J Nerv Ment Dis 198:213–219

    Article  PubMed  Google Scholar 

  • Motl RW et al (2010b) Symptom cluster and quality of life in multiple sclerosis. J Pain Symptom Manage 39:1025–1032

    Article  PubMed  Google Scholar 

  • Musgrave T et al (2011) The MAO inhibitor phenelzine improves functional outcomes in mice with experimental autoimmune encephalomyelitis (EAE). Brain Behav Immun 25:1677–1688

    Article  CAS  PubMed  Google Scholar 

  • Newland PK et al (2012) Symptom clusters in women with relapsing-remitting multiple sclerosis. J Neurosci Nurs 44:66–71

    Article  PubMed  Google Scholar 

  • Nistico R et al (2013) Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis. PLoS One 8:e54666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • O’Connor AB et al (2008) Pain associated with multiple sclerosis: systematic review and proposed classification. Pain 137:96–111

    Article  PubMed  Google Scholar 

  • Olechowski CJ et al (2010) A diminished response to formalin stimulation reveals a role for the glutamate transporters in the altered pain sensitivity of mice with experimental autoimmune encephalomyelitis (EAE). Pain 149:565–572

    Article  CAS  PubMed  Google Scholar 

  • Olechowski CJ et al (2013) Changes in nociceptive sensitivity and object recognition in experimental autoimmune encephalomyelitis (EAE). Exp Neurol 241:113–121

    Article  CAS  PubMed  Google Scholar 

  • Olechowski CJ et al (2009) Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encephalomyelitis (EAE). Pain 141:156–164

    Article  CAS  PubMed  Google Scholar 

  • Osterberg A et al (2005) Central pain in multiple sclerosis–prevalence and clinical characteristics. Eur J Pain 9:531–542

    Article  CAS  PubMed  Google Scholar 

  • Pachner AR (2011) Experimental models of multiple sclerosis. Curr Opin Neurol 24:291–299

    Article  PubMed  Google Scholar 

  • Papadopoulou A, Muller-Lenke N, Naegelin Y, Kalt G, Bendfeldt K, Kuster P et al (2013) Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler 19:1290–1296

    Google Scholar 

  • Patten SB et al (2005) Clinical correlates of CES-D depressive symptom ratings in an MS population. Gen Hosp Psychiatry 27:439–445

    Article  PubMed  Google Scholar 

  • Pollak Y et al (2002) Experimental autoimmune encephalomyelitis-associated behavioral syndrome as a model of ‘depression due to multiple sclerosis’. Brain Behav Immun 16:533–543

    Article  CAS  PubMed  Google Scholar 

  • Pollak Y et al (2003) The EAE-associated behavioral syndrome: I. temporal correlation with inflammatory mediators. J Neuroimmunol 137:94–99

    Article  CAS  PubMed  Google Scholar 

  • Pollak Y, Yirmiya R (2002) Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol 5:389–399

    Article  CAS  PubMed  Google Scholar 

  • Rabins PV et al (1986) Structural brain correlates of emotional disorder in multiple sclerosis. Brain 109(Pt 4):585–597

    Article  PubMed  Google Scholar 

  • Ransohoff RM (2012) Animal models of multiple sclerosis: the good, the bad and the bottom line. Nat Neurosci 15:1074–1077

    Article  CAS  PubMed  Google Scholar 

  • Ransohoff RM, Perry VH (2009) Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27:119–145

    Article  CAS  PubMed  Google Scholar 

  • Rivers TM et al (1933) Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J Exp Med 58:39–53

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rogers JM, Panegyres PK (2007) Cognitive impairment in multiple sclerosis: evidence-based analysis and recommendations. J Clin Neurosci 14:919–927

    Article  PubMed  Google Scholar 

  • Solaro C et al (2013) Pain and multiple sclerosis: pathophysiology and treatment. Curr Neurol Neurosci Rep 13:320

    Article  PubMed  Google Scholar 

  • Sumowski JF, Leavitt VM, Cohen A, Paxton J, Chiaravalloti ND, DeLuca J (2013) Retrieval practice is a robust memory aid for memory-impaired patients with MS. Mult Scler 19:1943–1946

    Google Scholar 

  • Thibault K et al (2011) Characterisation of sensory abnormalities observed in an animal model of multiple sclerosis: a behavioural and pharmacological study. Eur J Pain 15(231):e1–e16

    PubMed  Google Scholar 

  • Thornton AE et al (2002) Memory in multiple sclerosis: contextual encoding deficits. J Int Neuropsychol Soc 8:395–409

    Article  PubMed  Google Scholar 

  • Truini A et al (2013) A mechanism-based classification of pain in multiple sclerosis. J Neurol 260:351–367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wood B et al (2013) Prevalence and concurrence of anxiety, depression and fatigue over time in multiple sclerosis. Mult Scler 19:217–224

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Neuroscience, University of Alberta, Clinical Sciences Building, 8-120, Edmonton, AB, T6G 2G3, Canada

    Curtis Benson & Bradley J. Kerr

  2. Department of Anesthesiology and Pain Medicine, University of Alberta, Clinical Sciences Building, 8-120, Edmonton, AB, T6G 2G3, Canada

    Bradley J. Kerr

Authors
  1. Curtis Benson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bradley J. Kerr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bradley J. Kerr .

Editor information

Editors and Affiliations

  1. University of Kentucky Medical Center, Lexington, Kentucky, USA

    Bradley K. Taylor

  2. Centre for Pain Research, National University of Ireland, Galway, Ireland

    David P. Finn

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Benson, C., Kerr, B.J. (2014). Pain and Cognition in Multiple Sclerosis. In: Taylor, B., Finn, D. (eds) Behavioral Neurobiology of Chronic Pain. Current Topics in Behavioral Neurosciences, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2014_309

Download citation

Publish with us

Policies and ethics

Search

Navigation