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. 2003 Nov;79(937):627–633. doi: 10.1136/pmj.79.937.627

Chronic non-malignant musculoskeletal pain in older adults: clinical issues and opioid intervention

V Podichetty 1, D Mazanec 1, R Biscup 1
PMCID: PMC1742882  PMID: 14654573

Abstract

Musculoskeletal pain is common, frequently under-reported, and inadequately treated in the older adult. The objective of this article is to review the management of musculoskeletal pain syndromes in older adults emphasising the potential role of opioid agents in carefully selected patients. Systematic analysis of the relevant literature was done. Even in cognitively impaired patients, assessment of musculoskeletal pain is mandatory. An algorithm for musculoskeletal pain is presented emphasising a stepwise pharmacological approach in combination with an array of non-pharmacological therapies. Comorbid conditions may limit therapeutic choices, particularly in the elderly. Repeated assessment of pain levels as well as functional status is critical for optimal pain management.

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Selected References

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  1. Bamigbade T. A., Davidson C., Langford R. M., Stamford J. A. Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus. Br J Anaesth. 1997 Sep;79(3):352–356. doi: 10.1093/bja/79.3.352. [DOI] [PubMed] [Google Scholar]
  2. Bergner M., Bobbitt R. A., Carter W. B., Gilson B. S. The Sickness Impact Profile: development and final revision of a health status measure. Med Care. 1981 Aug;19(8):787–805. doi: 10.1097/00005650-198108000-00001. [DOI] [PubMed] [Google Scholar]
  3. Bernabei R., Gambassi G., Lapane K., Landi F., Gatsonis C., Dunlop R., Lipsitz L., Steel K., Mor V. Management of pain in elderly patients with cancer. SAGE Study Group. Systematic Assessment of Geriatric Drug Use via Epidemiology. JAMA. 1998 Jun 17;279(23):1877–1882. doi: 10.1001/jama.279.23.1877. [DOI] [PubMed] [Google Scholar]
  4. Bernabei R., Gambassi G., Lapane K., Landi F., Gatsonis C., Dunlop R., Lipsitz L., Steel K., Mor V. Management of pain in elderly patients with cancer. SAGE Study Group. Systematic Assessment of Geriatric Drug Use via Epidemiology. JAMA. 1998 Jun 17;279(23):1877–1882. doi: 10.1001/jama.279.23.1877. [DOI] [PubMed] [Google Scholar]
  5. Blaum Caroline S., Ofstedal Mary Beth, Liang Jersey. Low cognitive performance, comorbid disease, and task-specific disability: findings from a nationally representative survey. J Gerontol A Biol Sci Med Sci. 2002 Aug;57(8):M523–M531. doi: 10.1093/gerona/57.8.m523. [DOI] [PubMed] [Google Scholar]
  6. Borgbjerg F. M., Nielsen K., Franks J. Experimental pain stimulates respiration and attenuates morphine-induced respiratory depression: a controlled study in human volunteers. Pain. 1996 Jan;64(1):123–128. doi: 10.1016/0304-3959(95)00088-7. [DOI] [PubMed] [Google Scholar]
  7. Brosseau Lucie, Milne Sarah, Robinson Vivian, Marchand Serge, Shea Beverley, Wells George, Tugwell Peter. Efficacy of the transcutaneous electrical nerve stimulation for the treatment of chronic low back pain: a meta-analysis. Spine (Phila Pa 1976) 2002 Mar 15;27(6):596–603. doi: 10.1097/00007632-200203150-00007. [DOI] [PubMed] [Google Scholar]
  8. Chudler E. H., Dong W. K. The role of the basal ganglia in nociception and pain. Pain. 1995 Jan;60(1):3–38. doi: 10.1016/0304-3959(94)00172-B. [DOI] [PubMed] [Google Scholar]
  9. Crook J., Rideout E., Browne G. The prevalence of pain complaints in a general population. Pain. 1984 Mar;18(3):299–314. doi: 10.1016/0304-3959(84)90824-8. [DOI] [PubMed] [Google Scholar]
  10. Deal C. L., Moskowitz R. W. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Rheum Dis Clin North Am. 1999 May;25(2):379–395. doi: 10.1016/s0889-857x(05)70074-0. [DOI] [PubMed] [Google Scholar]
  11. Deyo R. A., Walsh N. E., Martin D. C., Schoenfeld L. S., Ramamurthy S. A controlled trial of transcutaneous electrical nerve stimulation (TENS) and exercise for chronic low back pain. N Engl J Med. 1990 Jun 7;322(23):1627–1634. doi: 10.1056/NEJM199006073222303. [DOI] [PubMed] [Google Scholar]
  12. Dory M. A. Arthrography of the lumbar facet joints. Radiology. 1981 Jul;140(1):23–27. doi: 10.1148/radiology.140.1.6454162. [DOI] [PubMed] [Google Scholar]
  13. Du Pen S. L., Peterson D. G., Williams A., Bogosian A. J. Infection during chronic epidural catheterization: diagnosis and treatment. Anesthesiology. 1990 Nov;73(5):905–909. doi: 10.1097/00000542-199011000-00018. [DOI] [PubMed] [Google Scholar]
  14. Dunbar S. A., Katz N. P. Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cases. J Pain Symptom Manage. 1996 Mar;11(3):163–171. doi: 10.1016/0885-3924(95)00165-4. [DOI] [PubMed] [Google Scholar]
  15. Ettinger D. S., Vitale P. J., Trump D. L. Important clinical pharmacologic considerations in the use of methadone in cancer patients. Cancer Treat Rep. 1979 Mar;63(3):457–459. [PubMed] [Google Scholar]
  16. Ezzo J., Hadhazy V., Birch S., Lao L., Kaplan G., Hochberg M., Berman B. Acupuncture for osteoarthritis of the knee: a systematic review. Arthritis Rheum. 2001 Apr;44(4):819–825. doi: 10.1002/1529-0131(200104)44:4<819::AID-ANR138>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  17. Feenstra Johan, Heerdink Eibert R., Grobbee Diederick E., Stricker Bruno H. Ch. Association of nonsteroidal anti-inflammatory drugs with first occurrence of heart failure and with relapsing heart failure: the Rotterdam Study. Arch Intern Med. 2002 Feb 11;162(3):265–270. doi: 10.1001/archinte.162.3.265. [DOI] [PubMed] [Google Scholar]
  18. Feinmann C. Pain relief by antidepressants: possible modes of action. Pain. 1985 Sep;23(1):1–8. doi: 10.1016/0304-3959(85)90223-4. [DOI] [PubMed] [Google Scholar]
  19. Felson D. T. The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study. Semin Arthritis Rheum. 1990 Dec;20(3 Suppl 1):42–50. doi: 10.1016/0049-0172(90)90046-i. [DOI] [PubMed] [Google Scholar]
  20. Ferrell B. A., Ferrell B. R., Osterweil D. Pain in the nursing home. J Am Geriatr Soc. 1990 Apr;38(4):409–414. doi: 10.1111/j.1532-5415.1990.tb03538.x. [DOI] [PubMed] [Google Scholar]
  21. Ferrell B. A., Ferrell B. R. Principles of pain management in older people. Compr Ther. 1991 Aug;17(8):53–58. [PubMed] [Google Scholar]
  22. Ferrell B. A., Ferrell B. R., Rivera L. Pain in cognitively impaired nursing home patients. J Pain Symptom Manage. 1995 Nov;10(8):591–598. doi: 10.1016/0885-3924(95)00121-2. [DOI] [PubMed] [Google Scholar]
  23. Ferrell B. A. Pain management in elderly people. J Am Geriatr Soc. 1991 Jan;39(1):64–73. doi: 10.1111/j.1532-5415.1991.tb05908.x. [DOI] [PubMed] [Google Scholar]
  24. Galer B. S. Neuropathic pain of peripheral origin: advances in pharmacologic treatment. Neurology. 1995 Dec;45(12 Suppl 9):S17–S36. doi: 10.1212/wnl.45.12_suppl_9.s17. [DOI] [PubMed] [Google Scholar]
  25. Haythornthwaite J. A., Menefee L. A., Quatrano-Piacentini A. L., Pappagallo M. Outcome of chronic opioid therapy for non-cancer pain. J Pain Symptom Manage. 1998 Mar;15(3):185–194. doi: 10.1016/s0885-3924(97)00352-7. [DOI] [PubMed] [Google Scholar]
  26. Hernández-Díaz S., Rodríguez L. A. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med. 2000 Jul 24;160(14):2093–2099. doi: 10.1001/archinte.160.14.2093. [DOI] [PubMed] [Google Scholar]
  27. Hochberg M. C., Altman R. D., Brandt K. D., Clark B. M., Dieppe P. A., Griffin M. R., Moskowitz R. W., Schnitzer T. J. Guidelines for the medical management of osteoarthritis. Part I. Osteoarthritis of the hip. American College of Rheumatology. Arthritis Rheum. 1995 Nov;38(11):1535–1540. doi: 10.1002/art.1780381103. [DOI] [PubMed] [Google Scholar]
  28. Hochberg M. C., Altman R. D., Brandt K. D., Clark B. M., Dieppe P. A., Griffin M. R., Moskowitz R. W., Schnitzer T. J. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis Rheum. 1995 Nov;38(11):1541–1546. doi: 10.1002/art.1780381104. [DOI] [PubMed] [Google Scholar]
  29. Ingram Sally S., Seo Pearl H., Martell Robert E., Clipp Elizabeth C., Doyle Martha E., Montana Gustavo S., Cohen Harvey J. Comprehensive assessment of the elderly cancer patient: the feasibility of self-report methodology. J Clin Oncol. 2002 Feb 1;20(3):770–775. doi: 10.1200/JCO.2002.20.3.770. [DOI] [PubMed] [Google Scholar]
  30. Jacox A., Carr D. B., Payne R. New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med. 1994 Mar 3;330(9):651–655. doi: 10.1056/NEJM199403033300926. [DOI] [PubMed] [Google Scholar]
  31. Jamison R. N., Anderson K. O., Peeters-Asdourian C., Ferrante F. M. Survey of opioid use in chronic nonmalignant pain patients. Reg Anesth. 1994 Jul-Aug;19(4):225–230. [PubMed] [Google Scholar]
  32. Jamison R. N., Raymond S. A., Slawsby E. A., Nedeljkovic S. S., Katz N. P. Opioid therapy for chronic noncancer back pain. A randomized prospective study. Spine (Phila Pa 1976) 1998 Dec 1;23(23):2591–2600. doi: 10.1097/00007632-199812010-00014. [DOI] [PubMed] [Google Scholar]
  33. Johansson A., Sjölund B. Nerve blocks with local anesthetics and corticosteroids in chronic pain: a clinical follow-up study. J Pain Symptom Manage. 1996 Mar;11(3):181–187. doi: 10.1016/0885-3924(95)00167-0. [DOI] [PubMed] [Google Scholar]
  34. Joranson David E., Carrow Grant M., Ryan Karen M., Schaefer Linda, Gilson Aaron M., Good Patricia, Eadie John, Peine Susan, Dahl June L. Pain management and prescription monitoring. J Pain Symptom Manage. 2002 Mar;23(3):231–238. doi: 10.1016/s0885-3924(01)00410-9. [DOI] [PubMed] [Google Scholar]
  35. Jurna I., Grossman W. The effect of morphine on mammalian nerve fibres. Eur J Pharmacol. 1977 Aug 15;44(4):339–348. doi: 10.1016/0014-2999(77)90308-9. [DOI] [PubMed] [Google Scholar]
  36. Lawrence R. C., Helmick C. G., Arnett F. C., Deyo R. A., Felson D. T., Giannini E. H., Heyse S. P., Hirsch R., Hochberg M. C., Hunder G. G. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998 May;41(5):778–799. doi: 10.1002/1529-0131(199805)41:5<778::AID-ART4>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  37. Leffler C. T., Philippi A. F., Leffler S. G., Mosure J. C., Kim P. D. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med. 1999 Feb;164(2):85–91. [PubMed] [Google Scholar]
  38. Leveille S. G., Ling S., Hochberg M. C., Resnick H. E., Bandeen-Roche K. J., Won A., Guralnik J. M. Widespread musculoskeletal pain and the progression of disability in older disabled women. Ann Intern Med. 2001 Dec 18;135(12):1038–1046. doi: 10.7326/0003-4819-135-12-200112180-00007. [DOI] [PubMed] [Google Scholar]
  39. Magni G., Caldieron C., Rigatti-Luchini S., Merskey H. Chronic musculoskeletal pain and depressive symptoms in the general population. An analysis of the 1st National Health and Nutrition Examination Survey data. Pain. 1990 Dec;43(3):299–307. doi: 10.1016/0304-3959(90)90027-B. [DOI] [PubMed] [Google Scholar]
  40. Magni G., Marchetti M., Moreschi C., Merskey H., Luchini S. R. Chronic musculoskeletal pain and depressive symptoms in the National Health and Nutrition Examination. I. Epidemiologic follow-up study. Pain. 1993 May;53(2):163–168. doi: 10.1016/0304-3959(93)90076-2. [DOI] [PubMed] [Google Scholar]
  41. Magni G., Schifano F., De Leo D. Pain as a symptom in elderly depressed patients. Relationship to diagnostic subgroups. Eur Arch Psychiatry Neurol Sci. 1985;235(3):143–145. doi: 10.1007/BF00380984. [DOI] [PubMed] [Google Scholar]
  42. Mangione K. K., McCully K., Gloviak A., Lefebvre I., Hofmann M., Craik R. The effects of high-intensity and low-intensity cycle ergometry in older adults with knee osteoarthritis. J Gerontol A Biol Sci Med Sci. 1999 Apr;54(4):M184–M190. doi: 10.1093/gerona/54.4.m184. [DOI] [PubMed] [Google Scholar]
  43. Marks R. M., Sachar E. J. Undertreatment of medical inpatients with narcotic analgesics. Ann Intern Med. 1973 Feb;78(2):173–181. doi: 10.7326/0003-4819-78-2-173. [DOI] [PubMed] [Google Scholar]
  44. Mayer D. J. Acupuncture: an evidence-based review of the clinical literature. Annu Rev Med. 2000;51:49–63. doi: 10.1146/annurev.med.51.1.49. [DOI] [PubMed] [Google Scholar]
  45. McAlindon T. E., LaValley M. P., Gulin J. P., Felson D. T. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000 Mar 15;283(11):1469–1475. doi: 10.1001/jama.283.11.1469. [DOI] [PubMed] [Google Scholar]
  46. McCaffery M. Pain control. Barriers to the use of available information. World Health Organization Expert Committee on Cancer Pain Relief and Active Supportive Care. Cancer. 1992 Sep 1;70(5 Suppl):1438–1449. doi: 10.1002/1097-0142(19920901)70:3+<1438::aid-cncr2820701536>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  47. McQuay H. J., Tramèr M., Nye B. A., Carroll D., Wiffen P. J., Moore R. A. A systematic review of antidepressants in neuropathic pain. Pain. 1996 Dec;68(2-3):217–227. doi: 10.1016/s0304-3959(96)03140-5. [DOI] [PubMed] [Google Scholar]
  48. Melding P. S. Is there such a thing as geriatric pain? Pain. 1991 Aug;46(2):119–121. doi: 10.1016/0304-3959(91)90064-5. [DOI] [PubMed] [Google Scholar]
  49. Messier Stephen P., Glasser Julie L., Ettinger Walter H., Jr, Craven Timothy E., Miller Michael E. Declines in strength and balance in older adults with chronic knee pain: a 30-month longitudinal, observational study. Arthritis Rheum. 2002 Apr 15;47(2):141–148. doi: 10.1002/art.10339. [DOI] [PubMed] [Google Scholar]
  50. Moulin D. E., Iezzi A., Amireh R., Sharpe W. K., Boyd D., Merskey H. Randomised trial of oral morphine for chronic non-cancer pain. Lancet. 1996 Jan 20;347(8995):143–147. doi: 10.1016/s0140-6736(96)90339-6. [DOI] [PubMed] [Google Scholar]
  51. Mukherjee D., Nissen S. E., Topol E. J. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001 Aug 22;286(8):954–959. doi: 10.1001/jama.286.8.954. [DOI] [PubMed] [Google Scholar]
  52. Onghena P., Van Houdenhove B. Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies. Pain. 1992 May;49(2):205–219. doi: 10.1016/0304-3959(92)90144-Z. [DOI] [PubMed] [Google Scholar]
  53. Page J., Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. Arch Intern Med. 2000 Mar 27;160(6):777–784. doi: 10.1001/archinte.160.6.777. [DOI] [PubMed] [Google Scholar]
  54. Parmelee P. A., Smith B., Katz I. R. Pain complaints and cognitive status among elderly institution residents. J Am Geriatr Soc. 1993 May;41(5):517–522. doi: 10.1111/j.1532-5415.1993.tb01888.x. [DOI] [PubMed] [Google Scholar]
  55. Passik S. D., Weinreb H. J. Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids. Adv Ther. 2000 Mar-Apr;17(2):70–83. doi: 10.1007/BF02854840. [DOI] [PubMed] [Google Scholar]
  56. Payne R. Practice guidelines for cancer pain therapy. Issues pertinent to the revision of national guidelines. Oncology (Williston Park) 1998 Nov;12(11A):169–175. [PubMed] [Google Scholar]
  57. Penninx B. W., Messier S. P., Rejeski W. J., Williamson J. D., DiBari M., Cavazzini C., Applegate W. B., Pahor M. Physical exercise and the prevention of disability in activities of daily living in older persons with osteoarthritis. Arch Intern Med. 2001 Oct 22;161(19):2309–2316. doi: 10.1001/archinte.161.19.2309. [DOI] [PubMed] [Google Scholar]
  58. Phillips A. C., Polisson R. P., Simon L. S. NSAIDs and the elderly. Toxicity and economic implications. Drugs Aging. 1997 Feb;10(2):119–130. doi: 10.2165/00002512-199710020-00005. [DOI] [PubMed] [Google Scholar]
  59. Portenoy R. K., Foley K. M. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain. 1986 May;25(2):171–186. doi: 10.1016/0304-3959(86)90091-6. [DOI] [PubMed] [Google Scholar]
  60. Preston K. L., Jasinski D. R., Testa M. Abuse potential and pharmacological comparison of tramadol and morphine. Drug Alcohol Depend. 1991 Jan;27(1):7–17. doi: 10.1016/0376-8716(91)90081-9. [DOI] [PubMed] [Google Scholar]
  61. Rimer B., Levy M. H., Keintz M. K., Fox L., Engstrom P. F., MacElwee N. Enhancing cancer pain control regimens through patient education. Patient Educ Couns. 1987 Dec;10(3):267–277. doi: 10.1016/0738-3991(87)90128-5. [DOI] [PubMed] [Google Scholar]
  62. Rowe J. W., Andres R., Tobin J. D., Norris A. H., Shock N. W. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol. 1976 Mar;31(2):155–163. doi: 10.1093/geronj/31.2.155. [DOI] [PubMed] [Google Scholar]
  63. Roy R. A psychosocial perspective on chronic pain and depression in the elderly. Soc Work Health Care. 1986 Winter;12(2):27–36. doi: 10.1300/j010v12n02_03. [DOI] [PubMed] [Google Scholar]
  64. Schnitzer Thomas J., American College of Rheumatology Update of ACR guidelines for osteoarthritis: role of the coxibs. J Pain Symptom Manage. 2002 Apr;23(4 Suppl):S24–S34. doi: 10.1016/s0885-3924(02)00372-x. [DOI] [PubMed] [Google Scholar]
  65. Scott P. V., Fischer H. B. Intraspinal opiates and itching: a new reflex? Br Med J (Clin Res Ed) 1982 Apr 3;284(6321):1015–1016. doi: 10.1136/bmj.284.6321.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Scotto di Fazano C., Vergne P., Grilo R. M., Bertin P., Bonnet C., Trèves R. Intérêt de la prévention des nausées et vomissements chez des patients traités par morphine pour des douleurs bénignes d'origine rhumatologique. Therapie. 2002 Sep-Oct;57(5):446–449. [PubMed] [Google Scholar]
  67. Scudds R. J., McD Robertson J. Empirical evidence of the association between the presence of musculoskeletal pain and physical disability in community-dwelling senior citizens. Pain. 1998 Apr;75(2-3):229–235. doi: 10.1016/s0304-3959(97)00224-8. [DOI] [PubMed] [Google Scholar]
  68. Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med. 1998 Jul 27;105(1B):31S–38S. doi: 10.1016/s0002-9343(98)00072-2. [DOI] [PubMed] [Google Scholar]
  69. Swan S. K., Rudy D. W., Lasseter K. C., Ryan C. F., Buechel K. L., Lambrecht L. J., Pinto M. B., Dilzer S. C., Obrda O., Sundblad K. J. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial. Ann Intern Med. 2000 Jul 4;133(1):1–9. doi: 10.7326/0003-4819-133-1-200007040-00002. [DOI] [PubMed] [Google Scholar]
  70. Thomas K. S., Muir K. R., Doherty M., Jones A. C., O'Reilly S. C., Bassey E. J. Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial. BMJ. 2002 Oct 5;325(7367):752–752. doi: 10.1136/bmj.325.7367.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Volmink J., Lancaster T., Gray S., Silagy C. Treatments for postherpetic neuralgia--a systematic review of randomized controlled trials. Fam Pract. 1996 Feb;13(1):84–91. doi: 10.1093/fampra/13.1.84. [DOI] [PubMed] [Google Scholar]
  72. Ward S. E., Goldberg N., Miller-McCauley V., Mueller C., Nolan A., Pawlik-Plank D., Robbins A., Stormoen D., Weissman D. E. Patient-related barriers to management of cancer pain. Pain. 1993 Mar;52(3):319–324. doi: 10.1016/0304-3959(93)90165-L. [DOI] [PubMed] [Google Scholar]
  73. Weissman D. E. Doctors, opioids, and the law: the effect of controlled substances regulations on cancer pain management. Semin Oncol. 1993 Apr;20(2 Suppl 1):53–58. [PubMed] [Google Scholar]
  74. Wilder-Smith C. H., Hill L., Osler W., O'Keefe S. Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis. Dig Dis Sci. 1999 Jun;44(6):1107–1116. doi: 10.1023/a:1026607703352. [DOI] [PubMed] [Google Scholar]
  75. Wolfe M. M., Lichtenstein D. R., Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999 Jun 17;340(24):1888–1899. doi: 10.1056/NEJM199906173402407. [DOI] [PubMed] [Google Scholar]
  76. Zacny J. P. Should people taking opioids for medical reasons be allowed to work and drive? Addiction. 1996 Nov;91(11):1581–1584. [PubMed] [Google Scholar]
  77. Zenz M., Strumpf M., Tryba M. Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage. 1992 Feb;7(2):69–77. doi: 10.1016/0885-3924(92)90116-y. [DOI] [PubMed] [Google Scholar]

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