NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation
Abstract
A combination therapy of morphine with an NMDA-receptor antagonist might be more effective than morphine without a NMDA-receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome (CRPS). In order to test the efficacy of this combination therapy we performed a double-blind randomized placebo-controlled study on patients suffering from CRPS of the upper extremity. We used functional magnetic resonance imaging during movement of the affected and unaffected upper hand before and after a treatment regimen of 49 days that contrasted morphine and an NMDA-receptor antagonist with morphine and placebo. We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing. Only the combination therapy reduced pain at rest and during movement, and disability. After treatment, activation in the contralateral primary somatosensory (cS1) and anterior cingulate cortex was significantly reduced when the affected hand was moved. Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex (S2). Our data suggest that the combination of morphine with an NMDA-receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS. The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA-receptor antagonist on cerebral pain processing with emphasis on sensory-discriminative aspects of pain.
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A previous double-blind randomized placebo-controlled study on CRPS patients with morphine and memantine showed pain reduction with concomitant changes in brain areas associated with pain.
“a previous, double-blind randomized placebo-controlled study on CRPS patients with morphine and memantine (NMDA-receptor antagonist) that showed pain reduction with concomitant changes in brain areas associated with pain [15].”
From Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy (2019) · cites this paper as [15]
Reducing pain facilitates psychological and physical rehabilitation in CRPS.
“The pharmacological intervention aimed to reduce pain to facilitate the psychological and physical rehabilitation [15].”
From Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy (2019) · cites this paper as [15]
A previous double-blind placebo-controlled study on memantine-morphine medication and physiotherapy for CRPS patients showed promising effects with decreased pain and neuroimaging findings with decreased activation in pain related areas.
“That study showed promising effects with decreased pain and neuroimaging findings with decreased activation in pain related areas.”
From Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy (2019) · cites this paper as [15]
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- Authors
- Gustin, S. M., Schwarz, A., Birbaumer, N., Sines, N., Schmidt, A. C., Veit, R., Larbig, W., Flor, H., & Lotze, M.
- Affiliations
- Heidelberg University (DE)
- University of Tübingen (DE)
- IRCCS San Camillo Hospital (IT)
- Universitätsmedizin Greifswald (DE)
- Corresponding author
- Lotze, M.
- Venue
- Pain
- Published
- 2010-10
- Volume
- 151
- Issue
- 1
- Pages
- 69-76
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2171946774
- Cited by
- 112
- References
- 40
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 3 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 4 · 2014: 6 · 2013: 12 · 2012: 10
- FWCI
- 12.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
- Keywords
- complex regional pain syndrome, neuropathic pain, morphine, NMDA receptor antagonists, combination therapy, primary somatosensory cortex, secondary somatosensory cortex, anterior cingulate cortex, nociceptive processing, analgesia, sensory-discriminative pain
- MeSH terms
- Adult, Aged, Analgesics, Analysis of Variance, Brain Mapping, Cerebral Cortex, Double-Blind Method, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Memantine, Middle Aged, Morphine, Oxygen, Pain, Pain Measurement, Reflex Sympathetic Dystrophy, Time Factors
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