Category Archives: Brain Changes Caused by Pain – Is This Reversible?

Adverse Changes in the Brain Caused by Chronic Pain – Is this Reversible If Pain is Eliminated?

Dear Pain Matters blog readers,

It is now known that chronic pain (eg nerve pain) changes the brain.  This is true regardless whether the pain mechanisms are peripherally and/or centrally mediated.

Thus, regardless whether the pain mechanisms reside in the periphery (e.g. in a limb) and/or centrally (in the spinal cord/brain), the brain undergoes significant, adverse changes as a result of severe and persistent pain.  This is called pain-induced cortical reorganization.

The good news is that IF this nerve pain can be blocked, via Nerve Block, pain medicine, surgery, and/or another effective treatment, the brain can change back to normal.

Several studies show this including an important study by Birbaumer et al (1997) involving 6 Phantom Limb Pain patients.

Not only was Birbaumer’s team able to show that:

(1) severe, unrelieved nerve pain (Phantom Limb Pain) causes pain-induced changes in the brain,

(2) but they also showed that these brain changes were reversible,

but only in those patients who ‘experienced a virtual elimination of current phantom pain attributable to anesthesia (quoting from Abstract).   

In other words, the successful, pain-relieving effects of the Nerve Block (Regional Anaesthesia via Brachial Plexus Blockade) was simultaneously reflected by (quoting from Abstract)a very rapid elimination of cortical reorganization‘ in the brain in 3/6 patients.

The most impressive results were observed in a 56 year old patient with severe Phantom Limb Pain who lost his upper limb 28 years earlier.  This man (‘Subject Pr3‘) underwent both:

(1) reversal of pain-induced cortical reorganization; and

(2) complete elimination of Phantom Limb Pain

within only 20 minutes after complete anaesthesia in his stump and shoulder!

NB  It is likely that the pain mechanisms were peripherally mediated in the 3 patients who had pain relief from the Nerve Block.

In summary, the Nerve Block was effective for 3/6 patients with Phantom Limb Pain.  Thus, pain-induced brain changes were rapidly reversed as a direct consequence of the pain-relieving effects of the Nerve Block in these 3/6 patients.  However, this did not happen in the latter 3/6 who did not obtain relief from the Nerve Block.

Thus, the brain appears to change ‘for the worse’ to reflect persistent pain.  On the other hand, the brain is also able to change back to normal if/when persistent pain is finally successfully blocked.


Here is another patient with Phantom Limb Pain named ‘Trevor’:

While Trevor suffered from severe Phantom Limb Pain prior to his Nerve Block, his residual pain is now managed, post-Nerve Block.  Quoting (go to 27:43 in the video link):

“….At that moment, it was instant pain relief for me.”

While this video does not show images of Trevor’s brain, I would bet 2 cents that Trevor’s brain also changed, both ‘before’ and ‘after’ his Nerve Block.


Here’s to less chronic pain in the world,

Sabina Walker


(1) Birbaumer et al; Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization; J. Neurosci (1997); 17(14), 5503-5508.

Click to access 5503.full.pdf

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

Dear Pain Matters blog readers,


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).  


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.


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



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.)



(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.

Click to access 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.

Click to access 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).

(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.

(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.


(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.