Multiple Sclerosis (MS) Pain Treatment Options

 

I have an MS patient who was in bad shape when I started to see her – was using a walker. With various measures, she was much better. What worked? Vit D2 50,000 u weekly, B12 injections 1000 mcg subcut injection every day or two, ketamine injections 2-3 times a week, Pramipexole and Sinemet – bedtime dopa  for restless legs, and local injection treatments have helped. Spironolactone may have helped as well.

The usual drugs in Chronic MS pain are well recorded elsewhere and have limited effectiveness. For example, Cymbalta effects are minor though there might be a subgroup responding.

Pain Pract. 2014 Nov;14(8):732-44. doi: 10.1111/papr.12127. Epub 2013 Oct 24.
A randomized, double-blind, placebo-controlled trial of duloxetine for the
treatment of pain in patients with multiple sclerosis.
Vollmer TL et al
https://www.ncbi.nlm.nih.gov/pubmed/24152240

Only about 1/4 of patients with neuropathic pain feel much better with usual opioids and other measures.
Severe Neuropathic Pain – Only 1/4 Respond to Standard Drug Protocols – What Else Is There?
http://painmuse.org/?p=2640

lyrica/gabapentin
antidepressants
anticonvulsants
antispasm drugs like blacofen

So what are some other options?

1) High does Vitamin D – found to help chronic pain:

Vitamin D – Could High Doses Help Pains?
http://painmuse.org/?p=4168

Use in MS has been found helpful at high dose 10,000/day – I’ve been using 50,000/week

Vitamin D – Could High Doses Help Pains?
http://painmuse.org/?p=4168

It has been found to help MS:

Sotirchos, Elias S., et al. “Safety and immunologic effects of high-vs low-dose cholecalciferol in multiple sclerosis.” Neurology 86.4 (2016): 382-390.

https://www.researchgate.net/profile/Keith_Van_Haren/publication/288836819_Safety_and_immunologic_effects_of_high-_vs_low-dose_cholecalciferol_in_multiple_sclerosis/links/56cc8b4c08ae1106370d9996.pdf

2) Frequent B12 injections sustains high enough blood/CSF levels to improve pains:

Chronic Back Pain Help – Forgotten B12 Injections and What Else Good For…
http://painmuse.org/?p=1543

Found helpful as well in MS:
Treatment of multiple sclerosis with lofepramine, l-phenylalanine and vitamin B12: mechanism of action and clinical importance: roles of the locus coeruleus and central noradrenergic systems
C Lode
Medical Hypotheses  Voume 59, Issue 5, November 2002, Pages 594–602
http://www.sciencedirect.com/science/article/pii/S030698770200261X

B12 shots have to be given every 1-3 days to maintain high  enough blood levels to help with pain – I have them give it subcutaneously like an insulin shot.

3) Ketamine which grow synaptic nodules so should in theory help prevent deterioration. Strong pain killing and anti-depressant effects:

Simulating Ketamine Infusions with Repeated Deloid Muscle Injections
http://painmuse.org/?p=4993

Depression is a Form of Pain and Ketamine May be a Cure if One Can Make It Last
http://painmuse.org/?p=1420

It stimulates growth of synaptic buds and nerve growth is the opposite of nerve degeneration.

4) Pramipexole – Newest is the finding that a Parkinson drug (trade name miripex) stops the mouse version of MS:

MS Help – prevents mouse model of MS by dampening brain inflammation:

Mol Neurobiol. 2017 Mar;54(2):1033-1045. doi: 10.1007/s12035-016-9717-5. Epub 2016 Jan 22.
Pramipexole, a Dopamine D2/D3 Receptor-Preferring Agonist, Prevents Experimental Autoimmune Encephalomyelitis Development in Mice.
Lieberknecht et al
http://s3.amazonaws.com/academia.edu.documents/44205510/Pramipexole__a_Dopamine_D2D3_Receptor-Preferring_Agonist_.pdf?AWSAccessKeyId=AKIAIWOWYYGZ2Y53UL3A&Expires=1491144312&Signature=6SXlGmnGR9MBJIUfLcbNb9Nstd4%3D&response-content-disposition=inline%3B%20filename%3DPramipexole_a_Dopamine_D2_D3_Receptor-Pr.pdf

———–

Chronic Pain Help – Pramipexole also helps pain in Fibromyalgia

Holman, Andrew J., and Robin R. Myers.
A randomized, double‐blind, placebo‐controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications.
Arthritis & Rheumatism 52.8 (2005): 2495-2505.
http://onlinelibrary.wiley.com/doi/10.1002/art.21191/full

It also was found to reduce FM pain by–2.48 ± 0.38 cm[/10](36%) in the pramipexole group and –0.71 ± 0.54 cm (9.4%) in the placebo group.”

———–

Chronic Depression Help  – Astounding, is its potential benefit in chronic depression by bunting brain inflammation

Neuropsychopharmacology (2017) 42, 363; doi:10.1038/npp.2016.217
Pramipexole in Treatment Resistant-Depression, Possible Role of Inflammatory Cytokines
Rodrigo Escalona et al
https://www.ncbi.nlm.nih.gov/pubmed/27909317

———–

Restless Leg syndrome – what was the tie breaker for use is that it is one of the prime drugs used in restless leg sydrome. Its usual use of pramipexole is for restless leg syndrome, and she  has this condition so it is a shoe-in for her.

Montplaisir, Jacques, et al.
Restless legs syndrome improved by pramipexole A double-blind randomized trial. Neurology 52.5 (1999): 938-938.
http://www.neurology.org/content/52/5/938.short

Other Treatment considerations:

5) Testosterone – One of the things I haven’t started yet is testosterone which is always low in both male and female patients – in latter unmeasurably low.

One patent study found it useful in chronic pain:
Transdermal gel compositions containing testosterone and their use for the treatment of fibromyalgia, chronic fatigue syndrome, muscle pain or decreased libido
Robert Gyurik, Hillary White
European patent publication number EP2000143 A3
http://www.google.co.ug/patents/EP2000143A3?cl=en

Also suggested helpful in MS:
Mol Neurobiol. 2016 Dec 13. [Epub ahead of print]

The Level of Testosterone, Vitamin D, and Irregular Menstruation More Important than Omega-3 in Non-Symptomatic Women Will Define the Fate of Multiple Scleroses in Future.
Tavakol S1,2, Shakibapour S3, Bidgoli SA4,5.
https://www.ncbi.nlm.nih.gov/pubmed/27966076

I use a gel like testin – in women I use 0.2 mls (measure with syringe first time and use same size thereafter)

6) Marijuana

Has been found some useful in chronic pain though drops VAS pain by only 1-1.5/10 points according to one talk I attended.

May helps pain in MS:

Rog, David J., et al.
Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.
Neurology 65.6 (2005): 812-819.
https://www.researchgate.net/profile/Tim_Friede/publication/7576991_Rog_DJ_Nurmikko_TJ_Friede_T_Young_CA_Randomized_controlled_trial_of_cannabis-based_medicine_in_central_pain_in_multiple_sclerosis_Neurology_65_812-819/links/00b7d5354f4c96fdf8000000.pdf

  • dropped pain by 2.5/10 versus 1.7 in placebo

Zajicek, John, et al. “Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.” The lancet 362.9395 (2003): 1517-1526.
https://www.researchgate.net/profile/Andrew_Nunn2/publication/9011336_Cannabinoids_for_treatment_of_spasticity_and_other_symptoms_related_to_multiple_sclerosis_CAMS_study_multicentre_randomised_placebo-controlled_trial/links/00463524ab96b1f11e000000/Cannabinoids-for-treatment-of-spasticity-and-other-symptoms-related-to-multiple-sclerosis-CAMS-study-multicentre-randomised-placebo-controlled-trial.pdf

  • 46-50% got  reduction of pain versus 30% in placebo

 

7) Swank diet – low fat diet – Canadian study – diet spanning decades on a low fat diet found those in early stage MS rarely progressed to a wheel chair vs commonly if not. It was ignored much to my amazement presumably because it was thought those who were not doing well, would automatically stop the diet. “Voltaire’s Bastards” (book on idiocy of  validation techniques) at work and I hate it.  After 34 years, the MS related death rate was 61% in the high fat group and only 20% in the low fat group. You will never see a study like this again – a recent one followed people for 1 year only and of course did not find much. Am I the only one who thinks this is stupid?  the best article was a 1970 article you can no longer get on line.

?Gluten – one site suggested gluten an issue. Came across a study suggesting it may be an issue in 10% cases. Would be looking for irritable bowel as risk factor.

8) Peripheral treatments
Botulinum –
lady had pain and spasticity of left leg and had botulinum into affected muscle – posterior tibialis; flexior digitorum longus

TRPVI receptors – these receptors are not only found in brain but also are the prime skin receptors linked to peripheral sensitized pain. Peripherally sensitized skin is seen in neuropathic pain and mixed pain syndromes. Perineural injections of D5W (I add 3% glycerin) are becoming popular for reducing pain.
Remarkable New Treatment – Injecting Over Tenderized Skin Nerves With Plain 5% Dextrose
http://painmuse.org/?p=3579

Recently, abnormal TRPVI receptor genes have been found in some MS cases:

J Neuroimmunol. 2017 Apr 15;305:172-174. doi: 10.1016/j.jneuroim.2017.02.007.
TRPV1 polymorphisms and risk of interferon β-induced flu-like syndrome in
patients with relapsing-remitting multiple sclerosis.
Buttari F

Nerve tract injections might help peripheral sensitized kin areas in MS

9) Major Mood Disorder – commonly find it gets in way of any improvement and find it needs addressing.

10) tDCS – daily 20 min direct current with 2.0 milliamp stimuation with anode over motor strip (C3 or C4)  opposite side to worst pain or left and other opposite forehead supraorbital. This is given for 5 days.
Mori, Francesco, et al.
Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis.
The journal of pain 11.5 (2010): 436-442.
http://www.jpain.org/article/S1526-5900(09)00715-9/abstract

11) Spironolactone – this lady had pain and edema in her leg and spironolactone was added as a water pill. However, it can have spectacular effects on Fibromyalgia pain sometimes  and patient believes it is helping her pain as well:
Breathtaking Option for Treatment Resistant Fibromyalgia
http://painmuse.org/?p=4054

12) Minocycline – a tetracycline known to effect glial cells, has recently been shown to prevent relapse after 6 months from 61% without to 33% with

http://www.cbc.ca/news/canada/calgary/minocycline-ms-multiple-sclerosis-calgary-research-1.4139877

 

Please comment on treatments that worked/did not work in MS.

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