Cancer pain, pathophysiology, characteristics and syndromes

In this study the pathophysiology and characteristics of cancer pain together with cancer pain syndromes and guidelines of management are reviewed. Tumour-associated pain may be nociceptive (somatic or visceral) if the sustaining mechanisms are related to ongoing tissue pathology, or neuropathic when pain is associated with injury to neural tissues. The mechanism by which tumours produce pain include obstruction of lymphatic and vascular channels, distension of a hollow viscous, oedema and tissue inflammation or necrosis. Injury to tissues results in the local release of numerous chemicals that mediate transmission of pain stimulus. Cancer pain syndromes result from one or more of three fundamental causes; direct tumour involvement of tissues, cancer-directed therapy, and mechanisms unrelated to cancer or its treatment. Cancer pain syndromes are also classified as acute or chronic. Cancer pain characteristics provide some of the data essential for syndrome identification. These characteristics include intensity, quality, distribution and temporal relationships. The principles of tumour-directed pain control include modifying the source of pain by treating the cancer and the inflammatory response to cancer, altering the central perception of pain and interfering with nociceptive transmission within the central nervous system.

Cancer pain; Cancer pain pathophysiology; Cancer pain characteristics; Cancer pain syndromes

[1] Zhukovsky D. S., Gorowski E., Hausdorif J., et al.: "Unmet analgesic needs in cancer patients". J. Pain Symptom. Manage, 1995, 10, 113.

[2] Cleeland C. S., Gonin R., Hatfield A. K., et al.: "Pain and its treatment in outpatients with metastatic cancer". N. Engl. J. M ed., 1994, 330, 592.

[3] Coyle N., Adelhardt J., Foley K. M., et al.: "Character of terminal illness in the advanced cancer patient: pain and other symptoms during the last four weeks of life". J. Pain. Symptom. Manage, 1990, 5, 83.

[4] Portenoy R. K., Miransky J., Thaler H. T., et al.: "Pain in ambulatory patients with lung and colon cancer. Prevelence and characteristics". Cancer, 1992, 70, 1616.

[5] Grand S., Zech D., Diefenbach C., et al.: "Prevalence and pattern of symptoms in patient with cancer pain: A prospective evaluation of 1635 cancer patients referred to a pain clinic". J. Pain. Symptom. Manage, 1994, 9, 372.

[6] Cleeland C.: "Research in cancer pain. What we know and what we need to know". Cancer, 1991, 67, 823.

[7] Task Force on Taxonomy. Classification of chronic pain. Descnptions of chronic pain syndromes and definitions of pain terms Seattle: !ASP Press, 1994.

[8] Fitzgibbon D. R., Chapman C. R.: "Cancer pain: Assessment and diagnosis". In: Loeser JD (ed). Bonica's Management of Pain. Philedelphia, Lippincott Williams and Wilkins, 2001, 623.

[9] Sherington C. S.: "The Integrative Action of the Nervous System" New York, Scribner, 1906.

[10] Turk D. C., Okifuji A.: "Pain terms and taxonomies of pain". In: Loeser JD (ed). Bonica's Management of Pain. Philedelphia, Lippincott Williams and Wilkins, 2001, 17.

[11] Raja S. N., Meyer R. A., Ringkamp M., Campbell J. N.: "Peripheral neural mechanisms of nociception". In: Wall PD, Melzack R (eds). Textbook of Pain. 4'" ed. Hong Kong, Churchill Livingstone, 1999, 11.

[12] DiRosa M., Giraud J. P., Willoughby D. A.: "Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine". J. Pathol., 1971, 104, 15.

[13] Khan A. A.,R aja S. N.,M anning D. C.,C ampbell J. N.,M eyer R A.: "The effects of bradykinin and sequence-related analogs on the response properties of cutaneous nociceptors in monkeys". Somatosens. Motor Res., 1992, 9, 97.

[14] Reeh P. W., Sauer S. K.: "Chronic aspects in peripheral nociception". In: Jensen TS, Turner JA. Wiesenfeld-Hallin Z (eds). Progress in Pain Research and Management. 8" ed. Seattle, IASP, 1997, 115.

[15] Steen K. H.,R eeh P. W., Anton F.,H andwerker H. O.: "Protons selectively induce long lasting exitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro". J. Neurosci., 1992, 12, 86.

[16] Steen K. H.,S teen A. E., Kreysel H. W.,R eeh P. W.: "Inflammatory mediators potentiate pain induced by experimental tissue acidosis". Pain, 1996, 66, 163.

[17] Lang E.,N ovak A.,R eeh P. W.,H andwerker H. 0.: "Chemosensitivity of fine afferents from rat skin invitro". J. Neurophysiol., 1990, 63, 887.

[18] Koda H., Minagawa M., Si-Hong L., Mizumura K., Kumazawa T.: "HI-receptor-mediated excitation and facilitation of the hear response by histamine in canine visceral polymodal receptors studied in vitro". J. Neurophysiol., 76, 1396.

[19] Simone D. A., Alreja M., LaMotte R. H.: "Psychophysical studies of the itch sensation and itchy skin ('Alloknesis') produced by intracutaneous injection of histamine". Somatosens. Motor Res., 1991a, 8, 271.

[20] Rueff A., Dray A.: "Sensitization of peripheral afferent fibres in the in vitro neonatal rat spinal cord-tail by bradykinin and prostaglandins". Neuroscience, 1993, 54, 527.

[21] Burnstock G.: "The past, present and future of purine nucleotides as signaling molecules". Neuropharmacol., 1997, 36, 1127.

[22] Bleehen T., Keele C. A.: "Observations on the algogenic actions of adenosine compounds on the human blister base preparation" Pain, 1997, 3, 367.

[23] Reeh P. W., Kress M.: "Boole's algebra and the gordian knot in peripheral nociception". Pain Forum, 1998, 7, 84.

[24] Kuby J.: "Immunology". In: Kuby J. (ed.), Immunology, 2nd ed., New York, WH Freeman, 1994, 297.

[25] Sorkin L. S., Xiano W-H., Wagner R., Myers R. R.: "Tumour necrosis factor-a induces ectopic activity in nociceptive primary afferent fibres". Neuroscience, 1997, 81, 255.

[26] Davidson E. M., Coggeshall R. E., Carlton S. M.: "Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test". Neuroreport, 1997, 8, 941.

[27] Carlton S. M., Harget G. L., Coggeshal R. E.: "Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin". Neurosci. Lett., 1995, 197, 25.

[28] Ault B., Hildebrand L. M.: "L-glutamate activites peripheral nociceptors.: Agents and Actions", 1993, 39, C142.

[29) Stein C., Hassan A. H. S., Przewlocki R., Gramsch C., Peter K., Herz A.: "Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation". Proceedings of the Nat. Acad. of Sciences USA, 1990, 87, 5935.

[30] Koltzenburg M., Lundberg L. E., Torebjiirk H. E.: "Dynamic and static components of mechanical hyperalgesia in human hairy skin". Pain,1992, 51, 207.

[31] Dougherty P. M., Palecek J., Paleckova V., Willis W. D.: "Neurokinin 1 and 2 antagonists attenuate the responses and NK I antagonists prevent the sensitization of primate spinothalamic tract neurons after intradermal capsaicin". J. Neurophysiol., 1994, 72, 1464.

[32] Dickenson A. H., Chapman V., Green G. M.: "The pharmacology of excitatory and inhibitory amino acide-mediated events in the transmission and modulation of pain in the spinal cord". Gen. Pharmacol., 1997, 28, 633.

[33] Woolf C. J., Bennet G. J., Doherty M., et al.: "Towards a mechanism based classification of pain". Pain, 1998, 77, 227.

[34] Caraceni A., Portenoy R. K., et al.: "An international survey of cancer pain characteristics and syndromes". Pain, 1999, 82, 263

[35] Ventafridda V., Caraceni A.: "Cancer pain classification: a controversial issue". Pain, 1991, 46, 1.

[36] Cherny N. I., Portenoy R. K.: "Cancer pain: principles of assessment and syndromes". In: Wall PD, Melzack R (eds.), Textbook of Pain, 4,h ed. Hong Kong, Churchill Livingstone, 1999,· 1017.

[37] Jacobson L., Mariano A. J.: "General considerations of chronic pain". In: Loeser JD (ed). Bonica's Management of Pain. Philedelphia, Lippincott Williams and Wilkins, 2001, 241.

[38] Cherny N. I., Catane R.: "Professional negligence in the management of cancer pain. A case for urgent reforms". Cancer, 1995, 76, 2181.

[39] World Health Organisation, Cancer Pain Relief, 2"'ed., World Health Organisation, Geneva, 1996.

[40] Vaimo A., Auvinen A.: "Prevalence of symptoms among patients with advanced cancer: An international collaborative study. Symptom Prevalence Group". J. Pain Symptom Manage., 1996, 12, 3.

[41] Giamberardino M. A., Vecchiet L.: "Visceral pain, referred hyperalgesia and outcome: new concepts". Eur. J. of Anaesthesia/., 1995, 10 (5), 61.

[42] Portenoy R. K., Komblith A. B., Wong 0., et al.: "Pain in ovanan cancer patients. Prevalence, characteristics, and associated symptoms". Cancer, 1994, 74, 907.

[43] Heller P. B.,M aletano J. H.,B undy B. N.,e t al.: "Clinical-pathologic study of stage IIB, III, and IVA carcinoma of the cervix: extended diagnostic evaluation for paraaortic node metastasis -a Gynecologic Oncology Group study". Gynecol. Oncol., 1990, 38, 425.

[44] Grond S., Zech D., Diefenbach C.,R adbruch L., Lehman K. A.: "Assessment of cancer pain: a prospective evaluation in 2266 cancer patients referred to a pain service". Pain, 1996, 64, 107.

[45] Cherny N. I., Arbit E., Jain S.: "Invasive techniques in the management of cancer pain". Hematol./Oncol. Clinics of No. America, 1996, 10 (1). 121.

[46] Levy M. N.: "Supportive oncology: forward". Semin. Oncol., 1994, 21, 699.

[47] Zech D. F., Grond S., Lynch J. et al.: "Validation of World Health Organization guidelines for cancer pain relief: a 10 year prospective study". Pain, 1995, 63, 65.

[48] Jacox A., Carr D. B., Payne R.: "New clinical practice guidelines for the management of pain in patients with cancer". N. Eng. J. Med., 1994, 330, 651.

[49] Ventafridda V., De Conno F., Panerai A. E., et al.: "Non-steroidal anti-inflammatory drugs as the first step in cancer pain therapy double blind, within-patient study comparing nine drugs". J. Int Med. Res., 1990, 18, 21.

[50] Practice Guidelines For Cancer Pain Management A Report By The American Society Of Anesthesiologists Task Force On Pain Management, Cancer Pain Section Anesthesiology 1996, 84, 1243.

[51] Fitzgibbon D.R., Chapman C.R.: "Cancer pain: Assessment and diagnosis". In: Loeser, JD (ed.), Bonica's Management of Pain. Philedelphia, Lippincott Williams and Wilkins, 2001, 659.