This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kiefer, R.-T. Articles by Jensen, T. S. Search for Related Content PubMed Articles by Kiefer, R.-T. Articles by Jensen, T. S.

---

LETTERS

The Analgesic Potency of NMDA-Antagonists—A Question of Mechanism-based Use and Timing?

Department of Anesthesiology, University of Tuebingen, Tuebingen, Germany Institute of Medical Psychology and Behavioral Neurobiology University of Tuebingen Tuebingen, Germany Institute of Medical Psychology and Behavioral Neurobiology University of Tuebingen Tuebingen, Germany and Dipartimento di Psicologica Generale Universitá di Padova Italy

To the Editor:

We would like to contribute to the discussion of the excellent work by Nikolajsen et al. (1), a well designed and carefully conducted study of the effect of a memantine on neuropathic pain after amputation or surgery. The authors concluded that memantine at a dosage of 20 mg/d does not reduce spontaneous nor evoked pain inpatients with nerve injury pain.

Successful treatment of chronic neuropathic pain remains difficult; often insufficient pain relief is achieved (2,3). However, subjects of Nikolajsen et al. (1) were patients with established chronic pain (duration between 1–28 yr). Data, suggesting a clinical role of N-methyl-D-aspartate (NMDA)-antagonists in chronic neuropathic pain are so far mainly based on single cases or a small series of patients and the use of ketamine (4–5). The exact clinical role of NMDA-blockade remains to be investigated (2,3,6,7). Strong experimental evidence points at a substantial role of the NMDA-receptor initiating central sensitization possibly leading to persistent pain-states (2,3,6–8). Consecutively, the use of NMDA-receptor antagonists in the early postinjury phase, or even before, may blunt or even preempt central sensitization and the subsequent development of chronic pain. From this point of view, the therapeutic efficacy of NMDA-antagonists once chronic pain is established seems to be questionable (2,3).

References

1. Nikolajsen L, Gottrup H, Kristensen AGD, Jensen TS. Memantine (a N-Methyl-D-Aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized, double-blinded, cross-over study. Anesth Analg 2000; 91: 960–6.[Abstract/Free Full Text]
2. Flor H, Birbaumer N, Sherman RA. Phantom limb pain. Pain Clinical Updates 2000; 8: 1–4.
3. Flor H, Birbaumer N. Phantom limb pain: cortical plasticity and novel therapeutic approaches. Curr Opin Anaesthesiol 2000; 13: 561–4.
4. Baron R. Neuropathische schmerzen: der lange weg vom mechanismus zur mechanismenorientierten therapie. Anaesthesist 2000; 49: 373–86.[Web of Science][Medline]
5. Nikolajsen L, Hansen CL, Nielsen J, et al. The effect of ketamine on phantom pain: a central neuropathic disorder maintained by peripheral input. Pain 1996; 67: 69–77.[Web of Science][Medline]
6. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999; 353: 1959–64.[Web of Science][Medline]
7. Birbaumer N, Flor H, Lutzenberger W, Elbert T. The corticalization of chronic pain. In: Bromm B, Desmedt JE, eds. Pain and the brain, Vol. 22: Advances in pain research and therapy. New York: Raven Press, 1995:331–44.
8. Yaksh TL, Hua XY, Kalcheva I, et al. The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proc Natl Acad Sci U S A 1999; 96: 7680–6.[Abstract/Free Full Text]

Response

Danish Pain Research Center Åarhus Kommunehospital Aarhus, Denmark

In Response:

We appreciate the thoughtful comments on our study by Kiefer et al. and agree that further research is needed to clarify the role of NMDA receptor antagonists in neuropathic pain.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kiefer, R.-T. Articles by Jensen, T. S. Search for Related Content PubMed Articles by Kiefer, R.-T. Articles by Jensen, T. S.