Einfluss der Alzheimer-Erkrankung auf die Schmerzverarbeitung

 

 Buy Article Permissions and Reprints

Zusammenfassung

Aus klinischen Studien ist hinlänglich bekannt, dass Patienten mit Morbus Alzheimer im Vergleich zur Altersgruppe deutlich weniger über Schmerzen berichten. Über die zugrunde liegenden Mechanismen des verminderten Schmerzberichtes weiß man hingegen nur wenig. Zu ihrer Aufdeckung sind experimentelle Studien unabdingbar, da hier Noxe und Schmerzerleben unabhängig voneinander zu erfassen sind. Wir berichten deshalb in dieser Übersichtsarbeit über experimentelle Befunde zum Schmerzerleben bei Alzheimer-Patienten. Es zeichnet sich ab, dass die Schmerztoleranzschwelle deutlich erhöht und die vegetative Schmerzreaktion teilweise erheblich vermindert ist. Die Schmerzschwelle und schmerzkorrelierten Hirnpotenziale zeigten sich hingegen weitestgehend unverändert. Wir diskutieren als mögliche Erklärungen hierfür altersbedingte Veränderungen des Schmerzerlebens und neuroanatomische Veränderungen im Rahmen der Alzheimer-Erkrankung. Insbesondere Atrophien im limbischen System könnten einen modifizierenden Einfluss auf das Schmerzerleben nehmen. Auch der Einfluss von alzheimerbedingten Einbußen in der Fähigkeit zur Schmerzkommunikation wird diskutiert.

Abstract

It is well known that patients with Alzheimer's disease report less pain in comparison to their age group. However, little is yet known about the underlying mechanisms causing the decreased pain report. In order to learn more about these mechanisms, experimental studies are indispensable, since only in experimental settings, noxious input and pain experience can be assessed independently. We therefore report on experimental data on pain perception in Alzheimer's disease in this review. The experimental data suggest that the threshold for pain tolerance is markedly increased and the autonomic pain reaction is, at least in part, considerably diminished. On the other hand, pain threshold and pain event-related brain potentials remain largely unchanged. As possible explanations we discuss age-related changes in pain perception and neuroanatomical changes in Alzheimer's disease. Particularly the atrophy of limbic structures may have a modifying impact on the pain experience. We also discuss what influence communicational deficits have on pain report.

Literatur

• 1 Ferrell B A, Ferrell B R, Rivera L. Pain in cognitively impaired nursing home patients.  J Pain Symptom Manage. 1995;  10 591-598
  CrossrefPubMedGoogle Scholar
• 2 Hanlon J T, Fillenbaum G G, Studenski S A, Ziqubu-Page T, Wall W E. Factors associated with suboptimal analgesic use in community-dwelling elderly.  Ann Pharmacother. 1996;  30 739-744
  PubMedGoogle Scholar
• 3 Scherder E J, Bouma A. Is decreased use of analgesics in Alzheimer disease due to a change in the affective component of pain?.  Alzheimer Dis Assoc Disord. 1997;  11 171-174
  PubMedGoogle Scholar
• 4 Fisher S E, Burgio L D, Thorn B E, Allen-Burge R, Gerstle J, Roth D L, Allen S J. Pain assessment and management in cognitively impaired nursing home residents: association of certified nursing assistant pain report, Minimum Data Set pain report, and analgesic medication use.  J Am Geriatr Soc. 2002;  50 152-156
  CrossrefPubMedGoogle Scholar
• 5 Marzinski L R. The tragedy of dementia: clinically assessing pain in the confused nonverbal elderly.  J Gerontol Nurs. 1991;  17 25-28
  PubMedGoogle Scholar
• 6 Feldt K S. Improving assessment and treatment of pain in cognitively impaired nursing home residents.  Annals of Long-Term Care: Clinical Care and Aging. 2000;  8 36-42
  PubMedGoogle Scholar
• 7 Huffman J C, Kunik M E. Assessment and understanding of pain in patients with dementia.  Gerontologist. 2000;  40 574-581
  CrossrefPubMedGoogle Scholar
• 8 Parmelee P A. Pain in cognitively impaired older persons.  Clin Geriatr Med. 1996;  12 473-487
  PubMedGoogle Scholar
• 9 Morrison R S, Siu A L. A comparison of pain and its treatment in advanced dementia and cognitively intact patients with hip fracture.  J Pain Symptom Manage. 2000;  19 240-248
  CrossrefPubMedGoogle Scholar
• 10 Calabrese P. Neuropsychologie der Alzheimer-Demenz. In: Calabrese P, Förstl H (Hrsg). Psychopathologie und Neuropsychologie der Demenz. Lengerich: Pabst Science Publishers 2000: 31-50
  Google Scholar
• 11 Farrell M J, Katz B, Helme R D. The impact of dementia on the pain experience.  Pain. 1996;  67 7-15
  CrossrefPubMedGoogle Scholar
• 12 Blomqvist K, Hallberg I R. Pain in older adults living in sheltered accommodation - agreement between assessments by older adults and staff.  J Clin Nurs. 1999;  8 159-169
  CrossrefPubMedGoogle Scholar
• 13 Cook A K, Niven C A, Downs M G. Assessing the pain of people with cognitive impairment.  Int J Geriatr Psychiatry. 1999;  14 421-425
  CrossrefPubMedGoogle Scholar
• 14 Chibnall J T, Tait R C. Pain assessment in cognitively impaired and unimpaired older adults: a comparison of four scales.  Pain. 2001;  92 173-186
  CrossrefPubMedGoogle Scholar
• 15 Gibson S J, Helme R D. Age-related differences in pain perception and report.  Clin Geriatr Med. 2001;  17 433-456
  PubMedGoogle Scholar
• 16 Cornu F. Perturbations de la perception de la douleur chez les dements degeneratifs.  Journal de Psychologie Normal et Pathologique. 1975;  72 461-472
  PubMedGoogle Scholar
• 17 Benedetti F, Vighetti S, Ricco C, Lagna E, Bergamasco B, Pinessi L, Rainero I. Pain threshold and tolerance in Alzheimer's disease.  Pain. 1999;  80 377-382
  CrossrefPubMedGoogle Scholar
• 18 Rainero I, Vighetti S, Bergamasco B, Pinessi L, Benedetti F. Autonomic responses and pain perception in Alzheimer's disease.  Eur J Pain. 2000;  4 267-274
  CrossrefPubMedGoogle Scholar
• 19 Gibson S J, Voukelatos X, Ames D, Flicker L, Helme R D. An examination of pain perception and cerebral event-related potentials following carbon dioxide laser stimulation in patients with Alzheimer's disease and age-matched control volunteers.  Pain Res Manag. 2001;  6 126-132
  PubMedGoogle Scholar
• 20 Jonsson C O, Malhammer G, Waldton S. Reflex elicitation thresholds in senile dementia.  Acta Psychiatr Scand. 1977;  55 81-96
  PubMedGoogle Scholar
• 21 Willer J-C. Comparative study of perceived pain and nociceptive flexion reflex in man.  Pain. 1977;  3 69-80
  CrossrefPubMedGoogle Scholar
• 22 Porter F L, Malhotra K M, Wolf C M, Morris J C, Miller J P, Smith M C. Dementia and response to pain in the elderly.  Pain. 1996;  68 413-421
  CrossrefPubMedGoogle Scholar
• 23 Hadjistavropoulos T, LaChapelle D L, MacLeod F K, Snider B, Craig K D. Measuring movement-exacerbated pain in cognitively impaired frail elders.  The Clinical Journal of Pain. 2000;  16 54-63
  CrossrefPubMedGoogle Scholar
• 24 Scherder E J, Bouma A. Visual analogue scales for pain assessment in Alzheimer's disease.  Gerontology. 2000;  46 47-53
  CrossrefPubMedGoogle Scholar
• 25 Krulewitch H, London M R, Skakel V J, Lundstedt G J, Thomason H, Brummel-Smith K. Assessment of pain in cognitively impaired older adults: a comparison of pain assessment tools and their use by nonprofessional caregivers.  J Am Geriatr Soc. 2000;  48 1607-1611
  PubMedGoogle Scholar
• 26 Basler H D, Bloem R, Casser H R, Gerbershagen H U, Griessinger N, Hankemeier U, Hesselbarth S, Lautenbacher S, Nikolaus T, Richter W, Schroter C, Weiss L. Ein strukturiertes Schmerzinterview für geriatrische Patienten A structured pain interview for geriatric patients.  Schmerz. 2001;  15 164-171
  CrossrefPubMedGoogle Scholar
• 27 Duffy F H, Albert M S, McAnulty G, Garvey A J. Age-related differences in brain electrical activity of healthy subjects.  Ann Neurol. 1984;  16 430-438
  CrossrefPubMedGoogle Scholar
• 28 Goodin D S, Aminoff M J, Mantle M M. Subclasses of event-related potentials: response-locked and stimulus-locked components.  Ann Neurol. 1986;  20 603-609
  CrossrefPubMedGoogle Scholar
• 29 Marsh J T, Schubarth G, Brown W S, Riege W, Strandburg R, Dorsey D, Maltese A, Kuhl D. PET and P300 relationships in early Alzheimer's disease.  Neurobiol Aging. 1990;  11 471-476
  CrossrefPubMedGoogle Scholar
• 30 Filipovic S R, Kostic V S. Utility of auditory P300 in detection of presenile dementia.  J Neurol Sci. 1995;  131 150-155
  CrossrefPubMedGoogle Scholar
• 31 Barrett G, Feinstein A, Jones S, Turano G, Youl B. Event-related potentials in the assessment of cognitive function in multiple sclerosis.  Electroencephalogr Clin Neurophysiol Suppl. 1999;  50 469-479
  PubMedGoogle Scholar
• 32 Hadjistavropoulos T, Craig K D, Martin N, Hadjistavropoulos H, McMurtry B. Toward a research outcome measure of pain in frail elderly in chronic care.  The Pain Clinic. 1997;  10 71-79
  PubMedGoogle Scholar
• 33 Ekman P, Frieses W V. The Facial Action Coding System. Palo Alto, CA: Consulting Psychologists' Press 1978
  Google Scholar
• 34 Prkachin K. The consistency of facial expression of pain: a comparison across modalities.  Pain. 1992;  51 297-306
  CrossrefPubMedGoogle Scholar
• 35 Hadjistavropoulos T, LaChapelle D L, MacLeod F K, Hale C, O'Rourke N, Craig K D. Cognitive functioning and pain reactions in hospitalized elders.  Pain Res Manage. 1998;  3 145-151
  PubMedGoogle Scholar
• 36 Hadjistavropoulos T, LaChapelle D L, Hadjistavropoulos H D, Green S, Asmundson G JG. Using facial expressions to assess musculoskeletal pain in older persons.  Eur J Pain. 2002;  6 179-187
  CrossrefPubMedGoogle Scholar
• 37 Möltner A, Hölzl R, Strian F. Heart rate changes as an autonomic component of the pain response.  Pain. 1990;  43 81-89
  CrossrefPubMedGoogle Scholar
• 38 Chakour M, Gibson S J, Helme R D. The effect of age on A delta and C fibre thermal pain perception.  Pain. 1996;  64 143-152
  CrossrefPubMedGoogle Scholar
• 39 Chapman W P, Jones C M. Variations in cutaneous and visceral pain sensitivity in normal subjects.  J Clin Invest. 1944;  23 81-91
  PubMedGoogle Scholar
• 40 Chapman W P. Measurements of pain sensitivity in normal control subjects and in psychoneurotic patients.  Psychosom Med. 1944;  6 252-257
  PubMedGoogle Scholar
• 41 Clark W C, Mehl L. Thermal pain: A sensory decision theory analysis of the effect of age and sex on various response criteria, and 50per cent pain threshold.  J Abnorm Psychol. 1971;  78 202-212
  PubMedGoogle Scholar
• 42 Gibson S J, Gorman M M, Helme R D. Assessment of pain in elderly using event related cerebral potentials. In: Bond MR, Charlton JE, Woolf CJ (Hrsg). Proceedings of the 4th World Congress on Pain. Amsterdam: Elsevier 1991: 527
  Google Scholar
• 43 Hall K RL, Stride E. The varying response to pain in psychiatric disorders: A study in abnormal psychology.  Br J Med Psychiatry. 1954;  27 48-60
  PubMedGoogle Scholar
• 44 Harkins S W, Price D D, Martelli M. Effects of age on pain perception: thermonociception.  J Gerontol. 1986;  41 58-63
  PubMedGoogle Scholar
• 45 Heft M W, Cooper B Y, O'Brien K K, Hemp E, O'Brien R. Aging effects on the perception of noxious and non noxious thermal stimuli applied to the face.  Aging Clin Exp Res. 1996;  8 35-41
  PubMedGoogle Scholar
• 46 Lautenbacher S, Strian F. Similarities in age differences in heat pain perception and thermal sensitivity.  Funct Neurol. 1991;  6 129-135
  PubMedGoogle Scholar
• 47 Meliala A, Gibson S J, Helme R D. The effect of stimulation site on detection and pain thresholds in young and older adults [abstract 188]. Vienna: Abstracts 9th World Congress on Pain 1999: p 559-P559
  Google Scholar
• 48 Procacci P, Bozza G, Buzzelli G, Della Corte M. The cutaneous pricking pain threshold in old age.  Gerontol Clin. 1970;  12 213-218
  PubMedGoogle Scholar
• 49 Procacci P. Methods for the study of pain threshold in man. In: Bonica JJ, Liebeskind JC, Albe-Fessard DG (Hrsg). Advances in Pain Research and Therapy (3). New York: Raven Press 1979: 781-792
  Google Scholar
• 50 Procacci P. A study of the cutaneous pricking pain threshold in normal man. In: Soulairac A, Cahn J, Charpentier J (Hrsg). Pain. London: Academic Press 1968: 223-224
  Google Scholar
• 51 Scudds R J, Scudds R A. A comparison of hot and cold pain thresholds between young subjects and young-elderly, middle-elderly and old-elderly subjects [ abstract 194]. Vienna: Abstracts 9th World Congress on Pain 1999: p 560-560
  Google Scholar
• 52 Sherman E D, Robbilard E. Sensitivity to pain in relationship to age.  J Am Geriartr Soc. 1964;  12 1037-1044
  PubMedGoogle Scholar
• 53 Sherman E D, Robillard E. Sensitivity to pain in the aged.  Can Med Assoc J. 1960;  83 944-947
  PubMedGoogle Scholar
• 54 Schulderman E, Zubek J P. Effect of age on pain sensitivity.  Percep Motor Skills. 1962;  14 295-301
  PubMedGoogle Scholar
• 55 Tremblay N, Allard N, Veilette Y. Effect of age on pain perception: Preliminary results [abstract 283]. Vienna: Abstracts 7th World Congress on Pain 1993: p 98
  Google Scholar
• 56 Birren J E, Schapiro H B, Miller J H. The effect of salicylate upon pain sensitivity.  J Pharmacol Exp Ther. 1950;  100 67-71
  PubMedGoogle Scholar
• 57 Harju E-L. Cold and warmth perception mapped for age, gender, and body area.  Somatosensory & Motor Research. 2002;  19 61-75
  PubMedGoogle Scholar
• 58 Kenshalo D R. Changes in the vestibular and somesthetic systems as a function of age. In: Ordy JM, Brizzee KR (Hrsg). Sensory systems and communication in the elderly. New York: Raven Press 1979: 269
  Google Scholar
• 59 Lautenbacher S, Nielsen J, Bär S, Strate P, Arendt-Nielsen L. Pain processing and somatosensation in young and elderly individuals. In: Abstracts - 10th World Congress on Pain Seattle: IASP Press 2002: p 304
  Google Scholar
• 60 Liou J T, Lui P W, Lo Y L, Liou L, Wang S S, Yuan H B, Chan K H, Lee T Y. Normative data of quantitative thermal and vibratory thresholds in normal subjects in Taiwan: gender and age effect.  Zhonghua Yi Xue Za Zhi (Taipei). 1999;  62 431-437
  PubMedGoogle Scholar
• 61 Meh D, Denislic M. Quantitative assessment of thermal and pain sensitivity.  J Neurol Sci. 1994;  127 164-169
  CrossrefPubMedGoogle Scholar
• 62 Pickering G, Jourdan D, Eschalier A, Dubray C. Impact of age, gender and cognitive functioning on pain perception.  Gerontology. 2002;  48 112-118
  CrossrefPubMedGoogle Scholar
• 63 Schumacher G A, Goodell H, Hardy J D. Uniformity of the pain threshold in man.  Science. 1940;  92 110-112
  PubMedGoogle Scholar
• 64 Yarnitsky D, Sprecher E, Zaslansky R, Hemli J A. Heat pain thresholds: normative data and repeatability.  Pain. 1995;  60 329-332
  CrossrefPubMedGoogle Scholar
• 65 Jensen R, Rasmussen B K, Pedersen B, Lous I, Olesen J. Cephalic muscle tenderness and pressure pain threshold in a general population.  Pain. 1992;  48 197-203
  CrossrefPubMedGoogle Scholar
• 66 Lasch H, Castell D O, Castell J A. Evidence for diminished visceral pain with aging: studies using graded intraesophageal balloon distension.  Am J Physiol. 1997;  272 G1-3
  PubMedGoogle Scholar
• 67 Mertz H, Fullerton S, Naliboff B, Mayer E A. Symptoms and visceral perception in severe functional and organic dyspepsia.  Gut. 1998;  42 814-822
  PubMedGoogle Scholar
• 68 Edwards R R, Fillingim R B. Age-associated differences in responses to noxious stimuli.  J Gerontol A Biol Sci Med Sci. 2001;  56 180-185
  PubMedGoogle Scholar
• 69 Zheng Z, Gibson S J, Khalil Z, Helme R D, McMeeken J M. Age-related differences in the time course of capsaicin-induced hyperalgesia.  Pain. 2000;  85 51-58
  CrossrefPubMedGoogle Scholar
• 70 Neri M, Agazzani E. Aging and right-left asymmetry in experimental pain measurement.  Pain. 1984;  19 43-48
  CrossrefPubMedGoogle Scholar
• 71 Tucker M A, Andrew M F, Ogle S J, Davison J G. Age-associated change in pain threshold measured by transcutaneous neuronal electrical stimulation.  Age Ageing. 1989;  18 241-246
  PubMedGoogle Scholar
• 72 Collins L G, Stone L A. Pain sensitivity, age and activity level in chronic schizophrenics and in normals.  Br Journal Psychiatr. 1966;  112 33-37
  PubMedGoogle Scholar
• 73 Harkins S W, Chapman C R. Age and sex differences in pain perception. In: Anderson B, Mattews B (Hrsg). Pain in the Trigeminal Region. Amsterdam: Elsevier Press 1977: 435-448
  Google Scholar
• 74 Harkins S W, Chapman C R. Detection and decision and factors in pain perception in young and elderly men.  Pain. 1976;  2 253-264
  CrossrefPubMedGoogle Scholar
• 75 Harkins S W, Chapman C R. The perception of induced dental pain in young and elderly women.  J Gerontol. 1977;  32 428-435
  CrossrefPubMedGoogle Scholar
• 76 Laitinen L V, Eriksson A T. Electrical stimulation in the measurement of cutaneous sensibility,.  Pain.. 1985;  22 139-150
  CrossrefPubMedGoogle Scholar
• 77 Lucantoni C, Marinelli S, Refe A. Course of pain sensitivity in aging. Pathogenetical aspects of silent cardiopathy.  Arch Gerontol Geriatr. 1997;  24 281-286
  CrossrefPubMedGoogle Scholar
• 78 Mumford J M. Pain perception in man on electrical stimulating the teeth. In: Soulairic A, Cahn J, Charpentier J (Hrsg). Pain. London: Academic Press 1968: 224-227
  Google Scholar
• 79 Mumford J M. Pain perception threshold and adaptation of normal human teeth.  Arch Oral Biol. 1965;  10 957-968
  PubMedGoogle Scholar
• 80 Notermans S LH. Measurement of pain threshold determined by electrical stimulation and its clinical application. Part I. Method and factors possibly influencing the pain threshold.  Neurology. 1966;  16 1071-1086
  PubMedGoogle Scholar
• 81 Helme R D, Gibson S J. Pain in the elderly. In: Jensen TS, Turner JA, Wiesenfeld-Hallin Z (Hrsg). Proceedings of the 8th World Congress on Pain. Seattle: ISAP Press 1997: 919-944
  Google Scholar
• 82 Walsh N E, Schoenfeld L, Ramamurthy S, Hoffman J. Normative model for cold pressor test.  Am J Phys Med Rehabil. 1989;  68 6-11
  PubMedGoogle Scholar
• 83 Woodrow K M, Friedmann G D, Siegelaub A B. Pain tolerance: differences according to age, sex and race.  Psychosoma Medicine. 1972;  34 548-556
  PubMedGoogle Scholar
• 84 Washington L L, Gibson S J, Helme R D. Age-related differences in the endogenous analgesic response to repeated cold water immersion in human volunteers.  Pain. 2000;  89 89-96
  CrossrefPubMedGoogle Scholar
• 85 Edwards R R, Fillingim R B, Ness T J. Age-related differences in endogenous pain modulation: a comparison of diffuse noxious inhibitory controls in healthy older and younger adults.  Pain. 2003;  101 155-165
  CrossrefPubMedGoogle Scholar
• 86 Melzack R, Casey K L. Sensory, motivational and central control determinants of pain. In: Kenshalo DR (Hrsg). The Skin Senses. Springfield, IL: Thomas 1968: 423-443
  Google Scholar
• 87 Ishii K. Clinical application of positron emission tomography for diagnosis of dementia.  Ann Nucl Med. 2002;  16 515-525
  CrossrefPubMedGoogle Scholar
• 88 Price D D. Psychological and Neural Mechanisms of Pain. New York: Raven Press 1988
  Google Scholar
• 89 Braak H, Braak E. Morphological changes in the human cerebral cortex in dementia.  J Hirnforsch. 1991;  3 277-282
  PubMedGoogle Scholar
• 90 Callen D J, Black S E, Caldwell C B. Limbic system perfusion in Alzheimer's disease measured by MRI-coregistered HMPAO SPET.  Eur J Nucl Med Mol Imaging. 2002;  29 899-906
  CrossrefPubMedGoogle Scholar
• 91 Chetelat G, Baron J C. Early diagnosis of Alzheimer's disease: contribution of structural neuroimaging.  Neuroimage. 2003;  18 525-541
  CrossrefPubMedGoogle Scholar
• 92 Rüb U, Del Tredici K, Del Turco D, Braak H. The intralaminar nuclei assigned to the medial pain system and other components of this system are early and progressively affected by the Alzheimer's disease-related cytoskeletal pathology.  J Chem Neuroanat. 2002;  23 279-290
  CrossrefPubMedGoogle Scholar
• 93 Scheff S W, Price D A. Alzheimer's disease-related synapse loss in the cingulate cortex.  J Alzheimers Dis. 2001 Oct;  3 495-505
  PubMedGoogle Scholar
• 94 Buchel C, Morris J, Dolan R J, Friston K J. Brain systems mediating aversive conditioning: an event-related fMRI study.  Neuron. 1998;  20 947-957
  CrossrefPubMedGoogle Scholar
• 95 Bromm B. Brain images of pain.  News Physiol Sci. 2001;  16 244-249
  PubMedGoogle Scholar
• 96 Bornhovd K, Quante M, Glauche V, Bromm B, Weiller C, Buchel C. Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study.  Brain. 2002;  125 1326-1336
  CrossrefPubMedGoogle Scholar
• 97 Tölle T R, Kaufmann T, Siessmeier T, Lautenbacher S, Berthele A, Munz F, Zieglgansberger W, Willoch F, Schwaiger M, Conrad B, Bartenstein P. Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis.  Ann Neurol. 1999 Jan ;  45 40-47
  CrossrefPubMedGoogle Scholar

1 Unter Schmerzbericht wird hier die verbale Äußerung von klinischen Schmerzen jedweder Genese verstanden.

Dipl.-Psych. M. Kunz

Klinik für Psychiatrie und Psychotherapie · Philipps-Universität Marburg

Rudolf-Bultmann Str. 8

35033 Marburg

Email: kunzm@med.uni-marburg.de