Dextropropoxyphene

The primary application of caffeine supplementation in pain control has been as an analgesic adjuvant when combined with certain analgesic drugs. This practice is supported by a number of double-blind studies. One of these studies found the potentiating action of caffeine on acetaminophen-induced pain relief to be similar to that experienced when an analgesic with a peripheral action (such as acetaminophen) is combined with another with a central action, in this case dextroproxyphen. By combining the peripherally-acting analgesic with caffeine instead of a centrally-acting analgesic, the side effects of central analgesics (such as drowsiness, constipation and nausea) can be avoided. (1)

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In a review of 30 clinical trials involving over 10,000 patients, the authors concluded that 40% higher dosages of aspirin, acetaminophen or salicylamide would be needed if they were not given in combination with a small dose of caffeine. (2) A similar adjuvant effect was found when caffeine was added to propyphenazone, (3) or to ibuprofen, a non-steroidal anti-inflammatory drug. (4) However, two recent meta-analyses of randomized controlled trials have questioned the efficacy of caffeine as an adjuvant as they found that caffeine added little to the analgesic effect of acetaminophen, (5) and was ineffective in enhancing the analgesic effect of aspirin. (6)

Studies have also investigated the efficacy of caffeine intake by itself, in treating acute pain. In a double-blind crossover study of 53 patients with non-migrainous headaches, subjects received 2 doses of caffeine, acetaminophen, 2 combinations of caffeine with acetaminophen, and placebo. Caffeine appeared to have an independent analgesic effect that remained significant when statistical adjustments were made for prior caffeine consumption and caffeine's effects on mood. Sixty-five milligrams of caffeine was just as effective as 648 milligrams of acetaminophen in relieving non-migrainous headache symptoms. (7)

However, when data on 131 patients with chronic back pain were reviewed, there were no significant differences between low, moderate and high caffeine users on subjective measures of pain severity or affective distress, (8) suggesting that chronic caffeine intake may be ineffective as a pain reliever.

Laboratory studies have investigated the mechanism by which caffeine may reduce pain. In vitro, instant coffee powders were shown to compete with naloxone for binding to opiate receptors. (9) This finding was not confirmed in vivo, however, as an animal study found that high doses of coffee, whether or not they contained caffeine, failed to show opiate-antagonizing activity. (10) More recent animal work has provided evidence suggesting that the antinociceptive effect of caffeine is mediated instead by central amplification of cholinergic transmission. (11) Moreover, adenosine is suspected to be the metabolite responsible for ischemic muscle pain, and caffeine is an adenosine receptor antagonist. (12)

A Warning

Caffeine can also have negative effects on pain. Acute caffeine withdrawal can cause distress due to "somatic dysfunction." (A term common to osteopathic physicians, somatic dysfunction refers to "impaired or altered function of related components of the somatic (body framework) system: skeletal, arthrodial, and myofascial structures, and related vascular, lymphatic and neural elements." (13)) Subjects in one study regularly consumed 300 mg or more of caffeine a day (found in about 2 eight-ounce cups of coffee or 6 eight-ounce cups of tea) and then abstained from caffeine for 4 days. The number of somatic dysfunctions were found to increase significantly during caffeine withdrawal. Even by day 4, most of the subjects had not fully returned to baseline. (14)

Also, a double-blind crossover study has found that caffeine ingestion may reduce the effectiveness of transcutaneous electrical nerve stimulation (TENS). (15) This finding suggests that patients trying TENS should avoid caffeine for a few days prior to the trial.

More information on the influence of nutrition on pain associated with a variety of illnesses can be found in the second edition of Dr. Werbach's classic SourceBook, Nutritional Influences on Illness--and in his updated and expanded CD-ROM with the same title. A free brochure on his books is available from Third Line Press Inc., 4751 Viviana Drive, Tarzana, California 91356, USA. (Phone: 800-916-0076; 818-996-0076; Fax: 818-774-1575; e-mail: tlp@third-line.com; Internet: www.third-line.com.)

References

1. Kuntz D, Brossel R. [Analgesic effect and clinical tolerability of the combination of paracetamol 500 mg and caffeine 50 mg versus paracetamol 400 mg and dextropropoxyphene 30 mg in back pain.] Presse Med 25(25):1171-4, 1996 (in French)

2. Laska EM et al. Caffeine as an analgesic adjuvant. JAMA 251(13):1711-18, 1984

3. Kraetsch HG et al. Analgesic effects of propyphenazone in comparison to its combination with caffeine. Eur J Clin Pharmacol 49(5):377-82, 1996

4. Forbes JA et al. Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain. Clin Pharmacol Ther 49(6):674-84, 1991

5. Zhang WY, Li Wan Po A. Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis. J Clin Pharm Ther 21(4):261-82, 1996

6. Zhang WY, Po AL. Do codeine and caffeine enhance the analgesic effect of aspirin?--A systematic overview. J Clin Pharm Ther 22(2):79-97, 1997

7. Ward N, Whitney C, Avery D, Dunner D. The analgesic effects of caffeine in headache. Pain 44(2):151-5, 1991

8. Currie SR et al. Caffeine and chronic low back pain. Clin J Pain 11(3):214-19, 1995

9. Boublik JH et al. Coffee contains potent receptor binding activity. Nature 301:246-8, 1983

10. Strubelt O et al. Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo. Experientia 42(1):35-7, 1986

11. Ghelardini C et al. Caffeine induces central cholinergic analgesia. Naunyn Schmiedebergs Arch Pharmacol 356(5):590-5, 1997

12. Myers DE et al. Hypoalgesic effect of caffeine in experimental ischemic muscle contraction pain. Headache 37(10):654-8, 1997

13. Glossary of Osteopathic Terminology. Glossary Review Committee, Educational Council on Osteopathic Principles of the American Association of Colleges of Osteopathic Medicine. Revised April 2002

14. Reeves RR et al. Somatic dysfunction increase during caffeine withdrawal. J Am Osteopath Assoc 97(8):454-6, 1997

15. Marchand S et al. Effects of caffeine on analgesia from transcutaneous electrical nerve stimulation. Letter. N Engl J Med 333(5):325-6, 1995

by Melvyn R. Werbach, MD

4751 Viviana Drive * Tarzana, California 91356 USA

Phone 818-996-0076 * Fax 818-774-1575

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