CRPS and Phantom Limb Pain Treated with Memantine or Memantine/Morphine

Dear Pain Matters blog readers,

COMPLEX REGIONAL PAIN SYNDROME (CRPS) AND MEMANTINE

Three (3) German studies (by the same team) showed promising results following:

– Memantine; or

– Memantine/Morphine Combination Therapy

in CRPS patients.

(1) 1st Study –

In the 1st study, pain decreased in 3 CRPS patients (CRPS duration = 1 to 7 months) following oral Memantine treatment for 8 weeks.  Specifically, there was NIL ‘resting pain’ at the 6-month follow-up (Sinis et al, 2006).

(2) 2nd Study –

In 6 CRPS patients, the duration of CRPS ranged from 4 to 23 months before Memantine Treatment.

Pain decreased significantly, and ‘continuous pain’ disappeared in all 6 CRPS patients after 8-week Memantine Treatment (as at 6-month follow-up).   Motor function also improved, together with Autonomic Nervous System changes, in all 6 patients (Sinis et al, 2007).

(3) 3rd Study –

This study involved 20 CRPS patients, as follows:

– 10 were given ‘Memantine/Morphine Combination Therapy’; and

– 10 were given ‘Placebo + Morphine’.

Duration of CRPS ranged from 6 to 36 months.

In all 10 CRPS patients, ‘pain at rest’ and ‘pain during movement’ decreased significantly following Memantine/Morphine Combination Treatment for 8 weeks. 

Interestingly, the 10 patients who were not given Memantine (the ‘Placebo + Morphine’ group) did not benefit as much.

Only the 10 patients given Memantine/Morphine Combination Treatment for 8 weeks had significant pain reduction and reduced disability.  

… and guess what else happened (that is very interesting)??

Memantine/Morphine Combination Treatment also resulted in significantly reduced activity in certain brain regions (Primary Somatosensory Cortex – contralateral side (S1) and Anterior Cingulate Cortex) when the CRPS-hand was moved!

Thus, Memantine/Morphine Combination Treatment resulted in decreased pain.  Furthermore, this decreased pain was mirrored via reduced activity in certain brain regions (S1, S2) (Gustin et al, 2010).  

PHANTOM LIMB PAIN AND MEMANTINE

Two (2) patients had severe Phantom Limb Pain as a consequence of severe lower leg injuries.  When oral Memantine treatment was given, these 2 patients had significant reduction in Phantom Limb Pain (Hackworth et al, 2008).  More studies are needed.

SUMMARY

In summary, treatment involving Memantine or Memantine/Morphine warrants more attention given its impressive results in:

– (a total of) 19 CRPS patients; and

– 2 patients with Phantom Limb Pain

who received either Memantine alone or Memantine/Morphine.  

Sabina Walker

PS  YOU DON’T HAVE TO READ THE FOLLOWING UNLESS YOU ARE VERY INTERESTED IN SCIENCE –

POSSIBLE MECHANISMS OF MEMANTINE IN NERVE PAIN

Memantine/Morphine Combination Therapy may alleviate painful symptoms of CRPS by reducing tumor necrosis factor-α (TNF) and other inflammatory mediators.  An animal study reported that administration of Memantine Hydrochloride decreases TNF expression in rats.  Studies are warranted to determine whether Memantine decreases local TNF in pain patients including CRPS patients.  (Memantine is widely known for its antagonistic effects on the NMDA receptor.)

(Please refer to Review Paper by Sabina Walker and Prof. Peter Drummond for further details.  In particular, please refer to pages 1796 – 1797, plus 4 Memantine-related References on pages 1805-1806, plus papers below.)

REFERENCES:

COMPLEX REGIONAL PAIN SYNDROME (CRPS) AND MEMANTINE

(1) Gustin SM, Schwarz A, Birbaumer N, et al. NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation. Pain 2010;151:69–76.

http://www.rsds.org/pdfsall/Gustin_Pain_2010.pdf

(2) Sinis N, Birbaumer N, Gustin S, et al. Memantine treatment of complex regional pain syndrome: A preliminary report of six cases. Clin J Pain 2007;23: 237–43.

http://www.rsds.org/pdfsall/Sinis_Birbaumer_Gustin.pdf

(3) Sinis N, Birbaumer N, Schwarz A, et al. Memantine und komplexes regionales Schmerzsyndrom (CRPS): Behandlungseffekte und kortikale Reorganisation (Memantine and complex regional pain syndrome (CRPS): Effects of treatment and cortical reorganisation). Handchir Mikrochir Plast Chir 2006;38:164–71. (in German).

http://www.researchgate.net/publication/239488100_Memantine_und_komplexes_regionales_Schmerzsyndrom_(CRPS)_Behandlungseffekte_und_kortikale_Reorganisation

(4) Sabina Walker, Peter D. Drummond; Implications of a Local Overproduction of Tumor Necrosis Factor-α in Complex Regional Pain Syndrome [Review Paper, 24 pages]; Pain Medicine (Dec 2011), 12 (12), 1784–1807.

In particular, please refer to pages 1796 – 1797, plus 4 Memantine-related References on pages 1805-1806.

http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4637.2011.01273.x/abstract

(5) Park et al; Antinociceptive Effect of Memantine and Morphine on Vincristine-induced Peripheral Neuropathy in Rats; Korean Journal of Pain (Sept 2010); 23(3):179-185.

doi: 10.3344/kjp.2010.23.3.179.

PHANTOM LIMB PAIN AND MEMANTINE 

(6) Hackworth et alProfound pain reduction after induction of memantine treatment in two patients with severe phantom limb pain; Anesth Analg (2008); 107:1377–1379.

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