Review Article| Volume 19, ISSUE 3, P420-432, May 1997

Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: constrating therapies for the treatment of chronic pain

  • Mark D. Aronson
    Address correspondence to: Mark D. Aronson, MD, Division of General Medicine and Primary Care, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215.
    Division of General Medicine and Primary Care, Beth Israel Hospital, Boston, Massachusetts U.S.A.
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.


      The treatment of chronic pain is an important function of physicians. In the United States, available drug treatments for chronic pain currently include simple analgesics such as acetaminophen, salicylates and other nonsteroidal anti-inflammatory drugs, traditional opioid drugs, and adjuvant agents (eg, antidepressants, anticonvulsants). Typically, the choice of a drug is made by balancing the indications for treatment, the clinical efficacy of the drug, and its toxicity. An understanding of the mechanism of action of these drugs helps to establish their role in therapy. Tramadol is an effective analgesic that works through a combined mechanism of weak mu receptor binding and the inhibition of serotonin and nonrepinephrine reuptake. Tramadol has a favorable adverse-effect profile and therefore is likely to have an important role in the management of chronic pain syndromes.


      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 to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Wall III, RT
        Use of analgesics in the elderly.
        Clin Geriatr Med. 1990; 6: 345-364
        • Frymoyer JW
        Predicting disability from low back pain.
        Clin Orthop. 1992; 279: 101-109
        • Hiraga K
        • Mizugachi T
        • Takeda F
        The incidence of chronic pain and improvement in pain management in Japan.
        Postgrad Med J. 1991; 67: 514-525
        • Egbert AM
        Help for the hurting elderly: Safe use of drugs to relieve pain.
        Postgrad Med. 1991; 89: 217-228
        • Magni G
        The use of antidepressants in the treatment of chronic pain. A review of the current evidence.
        Drugs. 1991; 42: 730-748
        • Whelton A
        • Hamilton CW
        Nonsteroidal anti-inflammatory drugs: Effects on kidney function.
        J Clin Pharmacol. 1991; 31: 588-598
        • Murray MD
        • Brater DC
        Nonsteroidal anti-inflammatory drugs.
        Clin Geriatr Med. 1990; 6: 365-397
        • Amadio Jr, P
        • Cummings DM
        • Amadio O
        Nonsteroidal anti-inflammatory drugs: Tailoring therapy to achieve results and avoid toxicity.
        Postgrad Med. 1993; 93: 73-88
        • Portenoy RK
        Cancer pain management.
        Semin Oncol. 1993; 20: 19-35
        • Jaffe JH
        • Martin JH
        Opioid analgesics and antagonists.
        in: Gilman AG Rall TW Nies AS Taylor P 8th ed. Goodman and Gilman's The Pharmacological Basis of Therapeutics. Pergamon Press, New York1990: 485-521
      1. Ultram®.
        in: Physicians' Desk Reference®. Medical Economics Company, Inc, Montvale, NJ1997: 1594-1596
        • Whitcomb DC
        • Block GD
        Association of acetaminophen hepatotoxicity with fasting and ethanol use.
        JAMA. 1994; 272: 1845-1850
        • Barkin RL
        Alternative dosing for tramadol aids effectiveness.
        Formulary. 1995; 30 (Letter): 542-543
        • Gabriel SE
        • Jaakkimainen L
        • Bombardier C
        Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs.
        Ann Intern Med. 1991; 115: 787-796
        • Griffin MR
        • Piper JM
        • Daugherty JS
        • et al.
        Nonsteroidal anti-inflammatory drug use and increased risk of peptic ulcer disease in elderly persons.
        Ann Intern Med. 1991; 114: 251-263
        • Roth SH
        NSAID gastropathy: A new understanding.
        Arch Intern Med. 1996; 156: 1623-1628
        • Fries JF
        • Miller SR
        • Spitz PW
        • et al.
        Toward an epidemiology of gastropathy associated with nonsteroidal anti-inflammatory drug use.
        Gastroenterology. 1989; 96: 647-655
        • Cummings DM
        • Amadio Jr, P
        A review of selected newer nonsteroidal anti-inflammatory drugs.
        Am Fam Phys. 1994; 49: 1197-1202
        • Clive DM
        • Stoff JS
        Renal syndromes associated with nonsteroidal anti-inflammatory drugs.
        NEJM. 1984; 310: 563-572
        • Whelton A
        Renal effects of over-the-counter analgesics.
        J Clin Pharmacol. 1995; 35: 454-463
        • Bush TM
        • Shlotzhauer TL
        • Imai K
        Nonsteroidal anti-inflammatory drugs: Proposed guidelines for monitoring toxicity.
        West J Med. 1991; 155: 39-42
        • Johnson AG
        • Nguyen TV
        • Day RO
        Do nonsteroidal anti-inflammatory drugs affect blood pressure?.
        Ann Intern Med. 1994; 121: 289-300
        • Hammack JE
        • Loprinzi CL
        Use of orally administered opioids for cancer-related pain.
        Mayo Clin Proc. 1994; 69: 384-390
        • Portenoy RK
        Chronic opioid therapy in nonmalignant pain.
        J Pain Symptom Manage. 1990; 5: S46-S62
        • Bushnell TG
        • Justins DM
        Choosing the right analgesic.
        Drugs. 1993; 46: 394-408
        • Inturris CE
        Management of cancer pain: Pharmacology and principles of management.
        Cancer. 1989; 63: 2308-2320
        • Lee CR
        • McTavish D
        • Sorkin EM
        Tramadol: A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states.
        Drugs. 1993; 46: 313-340
        • Grond S
        • Zech D
        • Lynch J
        • et al.
        Tramadol: A weak opioid for relief of cancer pain.
        Pain Clinic. 1992; 5: 241-247
        • Raffa RB
        • Friderichs E
        • Reinmann W
        • et al.
        Complementary and synergistics antinociceptive interaction between the enantiomers of tramadol.
        J Pharmacol Exp Ther. 1993; 267: 331-340
        • Raffa RB
        • Friderichs E
        • Reimann W
        • et al.
        Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an “atypical” opioid analgesics.
        J Pharmacol Exp Ther. 1992; 260: 275-285
        • Yaksh TL
        • Stevens CW
        Properties of the modulation of spinal nociceptive transmission by receptor selective agents.
        in: Dubner R Gebhart GF Bond MR Pain Reserach and Clinical Management. 3. Elsevier, Amsterdam1988: 418-435
        • Kayser V
        • Besson J-M
        • Guilbaud G
        Evidence for the noradrenergic component in the antinociceptive effect of the analgesic agent tramadol in an animal model of clinical pain, the arthritic rat.
        Eur J Pharmacol. 1992; 224: 83-88
        • Rauck RL
        • Ruoff GE
        • McMillen JI
        Comparison of tramadol and acetaminophen with codeine for long-term pain management in elderly patients.
        Curr Ther Res. 1994; 55: 1417-1431
        • Cossmann M
        • Wilsmann KM
        Effect and side-effect of tramadol. An open phase IV study with 7198 patients.
        Therapiewoche. 1987; 37: 3475-3485
        • Fechner R
        • Racenberg E
        • Castor G
        Klinische Untersuchungen über die wirkung von morphin, pentazocin, pethidin, piritramid und tramadol auf die atmung.
        Anästhesiol Intensivmed. 1985; 26: 126-132
        • Preston KL
        • Jasinski DR
        • Testa M
        Abuse potential and pharmacological comparison of tramadol and morphine.
        Drug Alcohol Depend. 1991; 27: 7-17
        • Kayser V
        • Besson J-M
        • Guilbaud G
        Effects of the analgesic agent tramadol in normal and arthritic rats: Comparison with the effects of different opioids, including tolerance and cross-tolerance to morphine.
        Eur J Pharmacol. 1991; 195: 37-45
        • Cami J
        • Lamas X
        • Farre M
        Acute effects of tramadol in methadone-maintained volunteers.
        Drugs. 1994; 47 (Suppl 1): 39-43