Diabetic Neuropathy

From Pain Medical Wiki
Jump to: navigation, search

Dietary Changes

mediaplayer>http://www.youtube.com/watch?v=3F5Sly9JQao</mediaplayer>

Recent study of vegan diet showed improvement in pain but did not show any benefit over B12 alone for pain. Mcgill questionnaire suggested it had less character though

Dm neuropathy.png

Diabetic Control

Exercise

  • India study: [1]
 - 8 wk moderate exercise (40-60% maximal heart rate)
 - 30% improvement in pain and significant improvement in quality of life

Smoking

Vitamins

B12 - px500

metformin lowers B12 levels


Vitamin D

  • Vitamin D deficency is twice as likely in cases of Diabetic neuropathy:[2] abstract here
  • recent article written on how reversal of vitamin D deficiency was associated with large improvement in diabetic neuropathy pain[3] free article here
-they suggest level under 30 ng/ml is a critically low level.
- 50,000 unit vitamin D weekly tripled subject's levels from 16 to 48 ng/ml {sold here as Osto-D2 50,000). I often use 50,000 weekly in high risk patients - that dose is non-toxic
- improved "dramatically with correction of the vitamin D deficiency"
  • They refer to a larger study of 51 type I diabetics with levels below 25 ng/ml - that develolped "a 50% decrease in pain scores with vitamin D repletion."[4] abstract here
  • vit D might help prevent diabetic neuropathy [5]
  • High Vit D protective against development of diabetes in metabolic syndrome cases[6] abstract here


Testosterone


Magnesium

Interventional

Caudal D5W - The Sweet Caudal

Experimental procedure where 10 mls D5W (dilute sugar) is injected caudally The Sweet Caudal Epidural.Though there might be concerns about 10 mls going high enough, alternative treatments with 10 mls solution with steroid has been used for L5/S1 and L4/5 disc levels satisfactorily.[7].

This is given epidurally - which means must attempt to not go more than
2 cm up the caudal canal

Female member of CAOM (need name) mentioned at Toronto 2012 meeting she was having good results with diabetic neuropathy.

Intrathecal B12

A Study[8] gave 2,500 ug Methylcobalamin in 10 mls saline intrathecally several times a month. abstract here

- Cases used had intraspinal B12 levels the same level as controls
- effect appeared within hours to one week and lasted from several months to four years 

- injected through a 0.45 um-pore filter - total injections ranged from 1-8 with an average of 3.5 - many were also given 1,500 ug/day to take orally - 11 bad cases - most had retinopathy, 3 had diabetic gangrene - "most experienced a burning sensation in legs within several hours of injection" " The most striking effects common to all patients were the relief of heaviness in the legs and the return of sensation. These effects were apparent in less than one week after the injections and lasted from several months to as long as four years." - they felt intrathecal transport of oral B12 was poor and intrathecal injections gave better results. They felt intraspinal levels had an anesthetic effect. - no observed side effects - resulted in dramatic relief of symptoms in legs - burning, paresthesia, and heaviness - This article is supported by two previous Japanese articles[9] [10]

Question comes to mind is whether this combined with D5W could give additional benefit.


Epidurals


Lumbar sympathetic Blocks


- Severe Case Diabetic neuropathy treated 2012[11]

-Lumbar blocks - at L3 "12mL of 1% Lidocaine and 20mg Triamcinolone on each side".

- Results on pain are plotted but included Thoracic pain issues which were treated with T8 bilateral paravertebral sympathetic nerve block, "which was performed in the classic fashion, under fluoroscopic guidance. A solution of 1% Lidocaine 10mL and 20mg Triamcinolone was injected on each side."

- Stated got good sustained relief of leg pains from blocks.

- Plot of pains that unfortunately include thoracic pain readings which become more an issue as time went on:

Symapthetic1.PNG

Medications

On the whole relatively disappointing. A drop in VAS pain scale of 3 is considered life changing - They do not achieve that difference from placebo.

This leaves one to consider several obvious issues:

- Other mechanical issues are going to contribute to the pains and need treatment: 
     - back problems, particularly post-laminectomy and spinal stenosis, 
     - Inflammatory Issues Sacroiliac, hip, knee, ankle and foot
     - Tibialis posterior issues with its myofascial aches in lower legs, tendonitis at ankle,   and associated 
tarsal tunnel syndrome at ankle. - Myofascial knots - gluteal, piriformis, hamstings and quads, gastrocnemius and soleus, and so on - leading to question of "Didn't anybody bother to turn out the lights?" - (when considering residual myofascial pains
left behind despite other treatments) - The need for polypharmacy to achieve results - The wisdom to know what drug works best for certain types of pains and for what type of patient (eg. the poorly sleeping
or depressed one) - How poverty contributes to suffering by keeping certain medications beyond their reach - eg -ALA below is a herbal as successful as other meds, and in select non-cardiac subjects (get a cardiologist to clear?)-
, could work as well but would again cost near $200/month
NOTE - From various studies, Placebo averages out to give a 27% drop in pain level by self. However, one study[12] accepted
anything greater than 20% as better than placebo.
In a medscape article on Tapendadol, it was mentioned that the FDA requires at least a 1/10 point VAS difference
between active drug and placebo[13] medscape link here for those who register
Recent analysis[14] has found that placebo effect determines 62% of the clinical effect.
I try to maxify this effect by printing out a study showing the virtues of a particular drud/treatment.
If the patient has a relation that has done well on a particualr medication, that works well as well.


Amitriptyline


Below resuilts of Amitriptyline and Desipramine on DM neuropathy and their side effects[15] free article here

Amit desp placebo.PNG

Amitrip desimsideeff.PNG

In a gabapentin study, before the cross over (unreliable after), amitriptyline did not fare well at all [16]: abstract here

Amit gp.PNG

In some the results were similar to placebo: In a study comparing Amitriptyline to electretherapy[17], amitriptyl;ine did not get over the 27% drop anticipated by a placebo. : "With amitriptyline, the pain scores decreased significantly from 3.8 ±0.1 to 2.9 ± 0.2 (P < 0.01)" (that is a 24% drop). To be fair, 4 weeks might of not been enough time to get full benefits, and it looks like 50 mg is a suboptimal dose - though many would not be able to tolerate higher due to side effects.

Amitript4wk.PNG


Another study [18] abstract herecomparing woefully inadequate doses of Amitriptyline to woefully inadequate doses of gabapentin showed rather lackluster effects assuming placebo reduces pain by 20%. Amitriptyline average 16 mg vs gabapentin average 218 mg/day

What was most striking was the fact only half maintained on treatment in either group.

Results:

Ami pregab.PNG

A study comparing Amitriptyline to Maprotiline[19](latter unusage because crossed over from amitriptyline)again showed mediocre results:


Amitript75 ludiomelstudy.PNG

Another study compared Amitriptyline 50 mg to Lamotrigine[20] - the effect after cross over are difficult to understand - is there a a residual beneficial effect from the former treatments - this might make their results unreliable.


Amitri lamotri.PNG

Another study compared Amitriptyline and Duloxetine[21] free article here

-58 people, 14 weeks -working up to 50 mg Amitriptyline and 60 mg Duloxetine


Amit dulox.PNG


CONCLUSION: Most studies did not find a differnce of more than 1 with placebo making it not recognizable as a painkilling agent by FDA. The cuple of studies did find it 1.4 - 1.5 VAS better than placebo but this falls short of the 2 thought to be clinically relevant [need put ref].:


Significance.PNG



Fluoxetine

NO good - Results are so disappointing with the Crossed over fluoxetine group still having more pain than placebo.


Fluoxetines.PNG

Fluoxetine se.PNG


Venlafaxine


A Small study[22] http://www.ncbi.nlm.nih.gov/pubmed/15288411

Placebo dropped pain to about 4.8 and venlafaxine to 3.3 - that amounts to only at 1.5/10 VAS pain difference.
The drug was supposedly more tolerable yet had a 15% discontinuation rate. Keeping the drug dose to 75 mg was no better than placebo.

- 15% discontinuation rate

Venlafaxine.PNG

Venlafaxine se.PNG


a recent rodent study found venlafaxine augmented analgesic properties of morphine[23]






Other Anti-depressants Table comparing some TCA and SSRI drugs effectiveness [24]

caption


Gabapentin

Dose used in one study started with 300 mg tid for 7 weeks - "continued in stepwise fashion (up to five titration
increments with target doses of 1,200, 1,800, 2,400, 2,700, and 3,600 mg/day) for non-responders until there was a response or 3,600 mg/day was reached" (ref below).
- mean dose reached 1936 mg.

Gabapentin results appear dose related [25]

Effects: caption


Side effects: - 48% cases -4.7% withdrawal rate - Somnolence 20.1% dizziness 16.6% - other side effects mild

They also consider gabapentin's sleep aid as a benefit


Pregabalin

[26]

Pregabalin Results, Pregabalin Side Effects, and its sleep effects:

Pregabalin.PNG

Pregabalin se.PNG

Pregabalin sleep.PNG


- their comment: "Treatment with pregabalin was not associated with serious AEs such as orthostatic hypotension 
and other risks common in elderly patients and patients with cardiac arrhythmias as associated with some TCAs, or
with gastrointestinal effects seen with nonsteroidal anti-inflammatory drug (NSAID) use.There are no known
pharmacokinetic drug interactions."

- Felt that 600 mg was better if tolerated: "while 37/81 (46%) and 39/81 (48%) of patients in the 300- and 600-mg/day
groups achieved a >50% reduction in mean score from study baseline to endpoint, 22/81 (27%) of patients in the 600-mg/day group achieved
a >70% reduction in score compared with 13/81 (16%) in the 300-mg/day group. This observation was supported by the increased proportion
of patients on the 600 mg/day dosage (54/78, 69%) who rated themselves on the PGIC as much improved or very much improved compared
with patients receiving 300 mg/day (44/79, 56%)".

-Sleep aid is played up despite fact a little amitriptyline, trazadone, or gabapentin could achieve that:


Comparison of Duloxetine, Pregabalin and Gabapentin

[27]

- Pregabalin showed better sleep benefits

Doses:

Gabapentin 300- 1800 (a low dose considering you can work up to 3,600 mg but that would probably take too long to reach)

Duloxetine 20-120 mg /day

Pregabalin 75 - 300 mg/day (a low dose since you can go up to 600 mg/day and one study on spinal neuropathic pain needed average 460 mg [28]) No significant difference in effectiveness between types at dose used - not great for duoxetine compared to half dose gabapentin

Preg gp dul1.PNG

Duo pg gp se.PNG

Duloxetine

- Goldstein(2005) [29] - abtract here
- Cymbalta at 60 or 120 mg   
- "safe and well tolerated with less than 20 percent discontinuation due to adverse events"
- Helped the sharp, shotting, stabbing pains most
- They felt only 0.2% of effect was mood enhancement.
- expensive and may not be on drug plan 

Treatment Effects below; Side effects - nausea drowsiness/dizziness the big ones.

Duloxetine.PNG

Duloxetinesideeffects1.PNG

Carbamazepine

Carbamazepine[30] Double blind cross over all but the 2 rashes continued treatment pain types included following:

caption

Unclear specifics but approximately 50% improvement; high incidence of neuralgic shooting pains in their group  might explain their benefits.

side effects:

caption

authors felt except for the 2 rashes, the side effects wained after a week. I suspect at the time it was take it or nothing else there so most stuck to it. Getting thru a week of dizziness seems to much for most - need to start low with the 100 mg chewables.

Tramadol

[31]

Effects and Side Effects:

Tramadol.PNG

Tramadol se.PNG


Tramadol with Acetaminophen (Tramacet) -Effects and side effects

Tramadol acetamin.PNG

Tramadol aceet se.PNG

Tapentadol

Placebo controlled trial with initial Open Laberl phase follwoed by double blind[32]

- Initiated at tapentadol ER 50 mg bid for 3 days 
- titrated to 100 mg bid for 3 days (minimum dose for study).
- then be titrated in 50 mg increments every 3 days 
- kept in the range of 100–250 mg bid
- could cut does by 50 mg bid as needed.

Results:

Tapentadol.PNG


This barely makes the 1/10 VAS pain difference required to be a minimal effect.

Side effects:

Tapentadol se.PNG

Lack of side effectrs matched the lack of efficacy. They had highly significant differences only because they recruited over 500 patients for study



Opioids

Oxycodone CR:[33]

Pain control is suspect because of high drop out rate (45%) potentially leaving only the best cases. Side Effects: - Constipation is the big one:

Oxycodone.PNG

Oxycodone se.PNG

- 10/22 withdrew mostly from side effects.

_ They started with 10 mg Oxycodone CR BID and worked up weekly to 40 mg bid - subjects crossed over at 4 weeks.

- Oxycodone CR was recently delisted here due to addiction concerns. Escalating oxycodone CR use in Ontario corresponded to escalating death rates from opioids.

Another study on control release oxycodone [34]

-Only 19/82 withdrew
- started with 10 mg of control released twice daily and ramped up by one extra twice daily every 3 days
until 60 mg bid though could be decreased to acceptable level if side effects

Oxycodone2.PNG

Oxycodone2 se.PNG


Methadone

Case study in a resistent subject highlighted how methadone could be used[35] free article here

- used following conversion from morphine - at 50-75% of conversion dose to start with. Methadone.PNG

If starting Opioid naive,:

-Start Opioid-naıve, frail, or elderly patients - 0.5–1 mg every 8 h;

-Normally start - 2.5–5 mg every 8 h.

-Breakthrough pain - at least 10–20% of daily dose given every 3–4 h PRN

-Night doses higher to deal with increased pain then

-Titration doses every 4–7 days,or reflecting braktrhough extra dosing

-Occasionally,use 6-h dosing in poor controlled

- side effect less than other opioids - if wait few days may go away. nausea, vomiting, constipation, sweating, itching, respiratory depression.

NSAID anti-inflammatory drugs

Both Ibuprofen 600 mg four times daily and Sulindac 200 mg twice daily were found to be better than placebo without affecting blood sugar or renal function.[36] abstract here


Alpha Lipoic Acid

Alpha Lipoic Acid

IV 600 mg/day best results (p<0.001):

[37]

-anti-oxidant
- Dissolved in 250 mls saline  - infused: "once daily over two 5-day periods (Monday to Friday) 
and one 4-day period (Monday to Thursday) during 3 consecutive weeks."

Results:


caption

Side Effects:

- 18.2% at 600 mg/day IV

headache (5/63) rare nausea/vomiting (seen at higher dose)

Unfortunately in this study, gains in neuropathy symptoms wained despite oral ALA 600 tid over subsequent 6 months
and were not different from placebo:

[38] Free full text

Oral ALA:

Multiple studies have shown benefits with just 600 mg/day for 5 weeks [39] http://www.hindawi.com/journals/ije/2012/456279/cta/


caption


- "lack of tolerability did not differ between placebo and treatment groups."


Problems:

- slightly more pricy than even pregabalin (above ref)
- Disconcertainly, heart rate and rhythm disorders over 4 years higher in ALA(6.9% ALA versus 2.7% placebo (P 0.047))[40]

Mexilitine

95 cases[41] free article here

-double blind randomized control trial

- start 75 mg tid for one week, then 150 mg tid for one week; then 225 mg tid if suggested by weight - average dose was 150 tid = 450 mg/day

EXCLUSION CRITERIA:
POSSIBILITY OF A PREGNANCY
NEUROPATHY OF OTHER ORIGIN
ALCOHOL OR DRUG ABUSE
VITAMIN B12 DEFICIENCY
DIABETICS WITH RENAL INSUFFICIENCY (CREATININE THRESHOLD VALUE 1.5 MG/DL)
CIRRHOSIS OF THE LIVER
HEPATITIS
SEVERE CHRONIC DAMAGE TO THE LIVER
MANIFEST CARDIAC INSUFFICIENCY
MYOCARDIAL INFARCTION <3 MO BEFORE
CARDIAC ARRHYTHMIA
PREVIOUSLY KNOW SICK-SINUS SYNDROME
UNCLARIFIED SYNCOPES
AV BLOCK
2ND AND 3RD DEGREE.
OCCLUSIVE ARTERIAL DISEASE, STAGE II ONWARDS

Results - scaled to 7/10 to start:

caption

Side Effects- unless dose was pushed over average dose of 450 mg/day, side effects were higher in placebo.

caption


Gastrointestinal and CNS symptoms appeared at higher doses.


A smaller earlier study - 16 cases treated with 10 mg/kg daily[42]

- randomized double bliind control crossover trial for 26 weeks

- mexiletine 150 mg first 3 days, 300 mg for next 3 days, then 10 mg/kg daily thereafter.

- 3/16 mild side effects - nausea, hiccups, tremor - two maintained on same dose; one reduced meds to 8 mg/kg

- dropped pains from 7 to 4.4 (scaled) -


Topirimate

Poor tolerance[43] - Only 112/214 completed study and side effectrs are listed below

Topiramate.PNG

Topiramate se.PNG


High Dose Dextromethorphan

DM ends up 24% better than placebo:[44]

caption

Lamotrigine 2006 study[45]

-Start with 25 mg and gradually work up to 400 mg
- potentially life threatening rash can occur - did get 2/26 cases (at weeks 4-7)-  rashes in study - none serious
- no other significant side effects
- Potentially very useful in depression - particulary in bipolar subjects
- p<0.001

Lamotrignine1.PNG

Lamotrigine se.PNG

Another study comparing amitriptyline and Lamotrigine[46]: They felt due to side effects, Lamotigine should be restricted to 25 mg BID.

Amitri lamotri.PNG


Sodium Valproate

48 Cases with type II DM[47] free article here

Their Exclusions: liver disease
pulmonary tuberculosis
thyroid disorders
uraemia
vitamin deficiency
hereditary and paraneoplastic neuropathy
alcoholism
patients on steroid therapy

Dose - started on valproate mg od (presumably hs) for 1 week - looked at nausea/vomiting, nystagmus/ataxia - If Ok gradually worked up to 500 mg TID

Results:


Valproate.PNG

Side Effects Included:

Valproate se.PNG

-Authors felt it was useful and well tolerated

Other Medications - ketamine


Overall conclusions

Treatment algorithms rely heavily on tricyclic antidepressants (shown to work poorly above, gabapentin and pregabalin. One of the lastest large sudies[48] abstract here used a better version of gabapentin up to 3600 and pregabalin at 300 mg/day. Results showed pregabalin did WORSE than placebo and high dose gabapentin NOT statistically better than placebo. People who rely on just medications for treatment of diabetic neuropathy are going to be in for a disappointment.

Gaba pregaba bad.PNG

Topicals

Amitriptyline and Ketamine


Capsaician


Nitroglycerin patches

Initially it had been found that Isosorbide dinitrate spray was able to reduce diabetic foot pains[49]. 50% reported benefit. This product has been withdrawn from the market. attempt has been made to use nitroglycerin patches, though not submitted to placebo controlled trial[50]

Design:
Start with 5

Polyurethane Film

Opsite Flexifix Roll

Opsite.PNG


Opsite has been found helpful in DM neuropathy[51] A recent article on subject[52] free article here stipulates optsite Flexifix rolls come in 5 and 10 cm widths and are 10 meters long. They can be wrapped around from toes up - usually to ankle though can go uptp knee. They state "Moleskin adhesive sheeting was added to the forefoot and heel contact areas on the plantar surface of the foot to increase the longevity of the film as walking on it can lead to breakdown of the material on the plantar surface." Excessive moisture inside leading to fungal infections and accumulation of shed skin are problems. The wrap is often left on 10 days and can get expensive. Moleskin adhesive pads are used to pad furniture and can be bought at a Dollar store or hardware store.


A second product is Lycra material fashioned into custom made stockings.

Lycra1.PNG


Third product is a stocking with some Lycra in it sold commercially as Swiss Venosan Legline 20

Legline.PNG

This product and how to measure and order is mentioned here on page 72: catalogue

Needling

Acupuncture


Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study B.B Abuaisha, J.B Costanzi, A.J.M Boulton Diabetes Research and Clinical Practice Volume 39, Issue 2, February 1998, Pages 115–121

6 courses classic acupunture over 10 weeks to both limbs

Acupuncture points: Liver 3 - web of the big toe

caption


Spleen 6 - 4 fingers above the medial malleolus From:

caption
caption




Spleen 9 - upper tibia caption



Stomach 36 - approximating to the head of fibula From: 'Why Are You Doing That Point?’ Stomach 36 By Sara Calabro [1] States "located on the shin. It’s found about a hand length below the patella, just outside the prominent tibia bone (see picture below). Having this point needled often produces a strong sensation that sometimes travels down the leg."

caption



"Standard references were consulted when choosing the acupuncture points. The precise points were confirmed by determining the position of the least skin resistance using a hand-held electrical conductance meter. Stainless steel disposable acupuncture needles (diameter 0.25 mm) are inserted into the skin to a depth of 3–4 mm. The first session was for 5 min and served to familiarize the patient with the acupuncture procedure while the rest of the sessions were for 20 min each. The second and third sessions were at weekly intervals. The fourth and fifth sessions were fortnightly. The sixth session was after 1 month. Thereafter, subsequent sessions took place when the patient felt the need for them, respectively."

Results - helped pain but did not help sleep

Acupuncture results.PNG

Acupuncture sleep.PNG

PENS Percutaneous Electical Nerve Stimulation (PENS)

Percutaneous Electrical Nerve Stimulation [53] appears to be westernized acupuncture - points are nearly identical but instead of acupuncture points they are described in terms of location to certain nerve trunks. When compared to acupuncture for postoperative pain, [54]abtract here some cases results are identical, some PENS better. PENS surg.PNG Near direct quotes:

"- standard, sterile, flexible solid 30-gauge, 1-inch acupuncture needles intramuscularly

- approximately 15–30-degree angles in points Sp6 and Sp8 bilaterally: - Sp6 at the posterior margin of the tibia, 3 units directly above the medial malleolus of the ankle, - Sp8 at the posterior margin of the tibia, 3 units below the inferior margin of the medial condyle of the tibia. (There are 13 units between the tip of the medial malleolus and the medial condoyle of the tibia.)Unit = fingerbreath - the needles were secured against the integument with medical tape and remained in place for the duration of the day until the second treatment 12 hours later, consistent with a morning and evening regimen on postoperative days 1 and 2. - The needles were removed at the end of each day by the nurse researchers." - Stimulation procedure - twice daily for 45-60 minutes - they did not directly say what frequency they used but since they varied pulse width up to 250 ms, one can assume it was near 4-5 hertz - pulse width was varied from 125-250 ms as such :"if the pulse width was set for the maximum output value (250ms), pulse width would decrease to 125 ms and then increase again to 250 ms in a period of 4 seconds. Thus, the nerve receptors would not become accustomed to the stimulation as quickly as would occur in a continuous mode."

For diabetic neruopathy they used following sites - look familiar?:


PENS.PNG

- "10 32-gauge (0.2 mm) stainless steel acupuncture-like needle probes (ITO, Tokyo, Japan) to a depth of 1–3 cm"
- stimulated at alternating frequencies of 15 and 30 Hz every 3 seconds
- maximum of 25 mamps res electrical stimulation
- biphasic square-wave pattern and a 
- pulse width of 0.5 ms in a continuous duty cycle.
- intensity  - highest tolerable level without muscle contractions
- 30 min three times a week for 3 wks

Results:- As can see 1/2 effectiveness gone within 1 week of no treatment so top ups would have to be at least weekly.

Pensrx last3.PNG



Intramuscular Stimulation


Other Needling

Treating Skin Sensitivity and Scars

Myofascial Release

Neuroprolotherapy


Stocking /bodyu wraps

Treating Myofacial Pains

Massage techniques


Injection techniques


Treat Back Pain Issues

Spinal stenosis and Postlaminectomy issues NB

Epidurals

Intrathecal midazolam


MacKenzie therapy


Manual medicine techniques


Treat Joint Pains

OA hip

OA knee


Treat Feet

Diabetic foot

Intermetatarsal bursitis


Pes Planus


IV and Injectable

B12

Lidocaine IV

Ketamine IV

Lidocaine and ketamine combined IV

Ketamine IM


Treat Restless Legs

Sleep Issues

disordered breathing


sleep apnea

Sleep study on Type 2 Diabetics[55] free article herefound sleep apnea common:

AHI 10+ - mild - may need CPAP - 48%

AHI 15+ definite - will need CPAP - 36% altogether = 29% females; 41% males

AHI 20 - severe - 29%

Another study[56]found sleep apena 2.8 times more likely in diabetics with neuropathy than those without abstract here. This means that in subjects with diabetic neuropathy, sleep apnea is more likely than not.Sleep apnea will encourage weight gain, encourage depression, and promote testosterone deficiency, all changes that will make DM neuropathy worse. (need ref) An epworth drowsiness scale should be done, and if >12 would indicate need for a sleep lab investigation.

Epworth home site:
How likely are you to doze off/fall asleep in the following circumstances?
0– never doze off
1 – Slight chance of dozing
2- moderate chance of dozing
3 – High chance of dozing

 Situation   -rate each from 0-3                                                                                                    

Sitting and Reading

Watching TV

Sitting inactive in a public place (e.g. a theater or meeting)

As a passenger in a car for an hour without a break

Lying down to rest in the afternoon when circumstances permit

Sitting and talking to someone

Sitting quietly after a lunch without alcohol

In a car, while stopped for a few minutes in the traffic

Score a total:

0-6 – good
7-8 – average
9-12 – abnormal
12+ - highly abnormal



Other sleep

Psychological Treatments

Cognitive Behavioural Therapy

Acceptance and Commitment

Mindfulness Meditation


Treatment Depression

Medications


BeHavioural


Cognitive


SAD light



Physiotherapy Techniques

Sciatic nerve stretching and Hamstring Transverse Mobs

Poster IASP Montreal 2010 [57]

  • Sciatic nerve stretch treatments help diabetic peripheral neuropathy pain and vibration sense further confirming nerve entrapments in diabetes
  • Sciatic nerve stretches were done something like this:
  • Leg is brought up to 90 degrees with knee bent and then knee straightened - 5 times each - 5 sets

Scaitic nerve stretch DM.png


  • Then transverse sciatic nerve massage - adjacent to but not on sciatic nerve - five reps, 5 sets again (sorry re pic quality)

Hamstring transverse stretch.png

  • People were given 1 hour sessions, one weekly for 5 weeks – there was a control group as well

results: Sciatic hamstring DN.png

Wax therapy

Chinese article [58] http://en.cnki.com.cn/Article_en/CJFDTOTAL-XDJH200835006.htm abstract here


- daily wax therapy - 40 minutes daily for 4 weeks (not sure how to make it 40 min except by repeated dipping)
- control was daily injectable 500 ug B12 and 100 mg B1  therapy.
- no reactions to treatments
- significant difference on symptoms,signs (p = 0.05 and NCV (nerve conduction studies)(p = 0.005) between the 
two groups. This is surprising since
frequent B12 shots is associated with beneficial effects of pains. - Their conclusion - "Wax therapy has significant curative effects on diabetic peripheral neuropathy" WARNING - Chinese articles may suffer from a
mis-reporting to "respected doctor" issue. Some years ago, methylene blue injection into disc was reported as an excellent way to treat disc disease but
the Chinese study did not stand up to other reports.

Therabath commonly advertised:Need other sources

caption

Canadian site: Canadian site for wax

Infrared (890 nm)gallium aluminum arsinide diode therapy

60 LED pads put below and above foot and on each side of calf above ankle for 40 minutes 3 times a week

Used a company that won't even list the cost of their pads so suggest get 850 nm LED IR Infrared Illuminator Light Lamp For CCTV Camera as long as you
can monitor units so they don't get too hot for skin (use at own risk!) Two units I can across on ebay:

caption

Each unit is 35-50 dollars which I imagine is much less than the undisclosed amount on other site.

Results: Did not give results for placebo treatment pain levels except to say they were P<0.001 for 6 and 12 treatments. I scaled results to Pain VAS starting at 7
and put placebo where most studies have found the placebo response goes - here is what I found:

caption

This would make results maybe VAS 1.3 better than placebo - which is comparible to what you get with some drugs.

Didn't work quite as well in subjects with numb feet.

About 1/2 reported improvement of sensation and balance.

They did not have any info on "durability" of treatment response though I would suspect weekly top-ups might be necessary.

Postural

Exercise

Laser

Ultrasound and massage

Transcutaneous Electical Nerve Stimulation (TENS)

studies:

Study one:[59]free article here

- 4-70 hz - 4 ms pilse - to maximum comfort - 30 minutes daily - 4 pads - two above knee - medial and lateral quads

        - two below knee - fibular neck and 3 " below popliteal space in medial gastrocnemius

- 4 weeks

results:

caption

- If scaled to start at 7, dropped to 4.4/10

Study 2 - Turkish study with pad applied in back[60] free pdf clickable here The idea for using lumbar pads came from a physiotherapy case article[61] This early reference put their pads single channel (2 pads) 1.3 cm (1⁄2 in) lateral to the posterior superior iliac spine each side.

Present study - 80 hz; 30 minutes daily;  "Double channel TENS device ...with four electrodes was used. After skin cleaning and applying hydrophilic gel to the electrodes, the electrodes
were bilaterally applied 3 cm lateral to the vertebral column on the lumbo sacral region."

Results:

caption

Study 3: - a long term study:[62]

- H wave machine with biphasic, exponentially decaying waveforms - 2-70 hz, 4 msec.; 4 pads - no info on usage time or positioning pads as just a home survey. 
- Followed for average 1.7 years
- Clamined a 2/10 mm drop in VAS on scale 0-10; this is not much better than the 1.9 anticipated from placebo
- However, suggested 70% were helped some and would have hardly stuck to it if it did not.


Trial with stocking electrodes 50 micoramp stimulated (small amount) 8 hours a night for 6 weeks did not fair better than control[63]

Spinal Stimulation

Diabetes Care. 2014 Sep 11. pii: DC_140684. [Epub ahead of print] Spinal Cord Stimulation and Pain Relief in Painful Diabetic Peripheral Neuropathy: A Prospective Two-Center Randomized Controlled Trial. Slangen R et al [2] RESULTS: Trial stimulation was successful in 77% of the SCS patients. Treatment success was observed in 59% of the SCS and in 7% of the BMT patients (P < 0.01). Pain relief during daytime and during nighttime was reported by 41 and 36% in the SCS group and 0 and 7% in the BMT group, respectively (P < 0.05). Pain and sleep were "(very) much improved" in 55 and 36% in the SCS group, whereas no changes were seen in the BMT group, respectively (P < 0.001 and P < 0.05). One SCS patient died because of a subdural hematoma.

CONCLUSIONS: Treatment success was shown in 59% of patients with PDPN who were treated with SCS over a 6-month period, although this treatment is not without risks.

Claudication Circulation Problems

Treat Tarsal Tunnel Syndrome

Innovative Techniques

Brain and spinal magnetic stimulation

Pulsed radiofrequency


Steroids in Diabetic Amyotriophy


Unproven Treatments

Melatonin

In experimental model of diabetic neuropathy[64] melatonin, alone or combined with nicotinamide (B3 derivative) ameliorated symptoms. Doses of melatonin were huge (3-10 mg/kg) where in an adult all I have ever used is max 12 mg at bedtime for sleep.



Epson salt soaks

Have on pateint who uses it for his neuropathy (not diabetic).

Warning was included in one patent application [65] free article herethat "epsom salts have been applied topically in low concentration as a wet soak, because a soak using a saturated epsom salt solution for longer than about fifteen minutes will likely cause local dermatitis" - so use of dilute warm soaks - Have no further info on its use - any comments?


Chi Machine

Rhythmically moves legs back and forth. Used to treat lymphedema but I have one patient with waldenstrom macroglobulinemia neuropathy that finds it removes 75% of his pain with a 20 minute use (testimonial is not proven though...)

caption

References

  1. Qual Life Res. 2013 Dec in press. Effect of aerobic exercise on quality of life in population with diabetic peripheral neuropathy in type 2 diabetes: a single blind, randomized controlled trial.Dixit S, Maiya A, Shastry B. http://www.ncbi.nlm.nih.gov/pubmed/24326731
  2. 7.L. H. Soderstrom, S. P. Johnson, V. A. Diaz, and A. G. Mainous, “Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001–2004 NHANES,” Diabetic Medicine, vol. 29, no. 1, pp. 50–55, 2012.
  3. Case Report Endocrinol. 2012;2012:165056. Reversal of the Symptoms of Diabetic Neuropathy through Correction of Vitamin D Deficiency in a Type 1 Diabetic Patient. Bell DS.
  4. 9.P. Lee and R. Chen, “Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain,” Archives of Internal Medicine, vol. 168, no. 7, pp. 771–772, 2008
  5. 2.A. G. Pittas, J. Lau, F. B. Hu, and B. Dawson-Hughes, “The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 6, pp. 2017–2029, 2007
  6. 2.A. G. Pittas, J. Lau, F. B. Hu, and B. Dawson-Hughes, “The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 6, pp. 2017–2029, 2007
  7. J Spinal Disord Tech. 2007 Feb;20(1):49-52.Caudal epidural injection for L4-5 versus L5-S1 disc prolapse: is there any difference in the outcome? Mohamed MM, Ahmed M, Chaudary M.
  8. Clin Ther. 1987;9(2):183-92.Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy. Ide H, Fujiya S, Asanuma Y, Tsuji M, Sakai H, Agishi Y
  9. Yoshida K, Katoh Y, Waseda et al. Effect of intrathecal injection of vitamin B12 on diabetic neuropathy. Horumon to Rinsho 1981. 29(suppl): 162-165
  10. Kawamuurs T, Nisahida T, Sano T. et al. Effect of intrathecal administration fo active type of vitamin B12 on diabetic peripheral neuropathy in patients with resistent subjective symptoms. Rinsho to Kenkyu 1982; 59:2985-2988.
  11. Case Rep Anesthesiol. 2012;2012:285328.Sympathetic blocks provided sustained pain relief in a patient with refractory painful diabetic neuropathy. Cheng J, Daftari A, Zhou L.
  12. A Comparison of Amitriptyline and Maprotiline in the Treatment of Painful Polyneuropathy in Diabetics and Nondiabetics.Clinical Journal of Pain December 1997; 13(4) 313-323; Vrethem, Magnus; Boivie, Jörgen; Arnqvist, Hans M.D.; Holmgren, Helen M; Lindström, Torbjörn M.D.; Thorell, Lars-Håkan
  13. FDA Approves Tapentadol ER for Diabetic Neuropathy. Pauline Anderson. Medscape Aug 29, 2012
  14. PAIN 152(8), August 2011, 1709–1717. Systematic review: Placebo response in drug trials of fibromyalgia syndrome and painful peripheral diabetic neuropathy—magnitude and patient-related predictors Winfried Häusera, Eva Bartram-Wunna, Claas Bartrama, Henriette Reinecke, Thomas Tölle
  15. N Engl J Med. 1992 May 7;326(19):1250-6.Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dubner R.
  16. Arch Intern Med. 1999 Sep 13;159(16):1931-7. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Morello CM, Leckband SG, Stoner CP, Moorhouse DF, Sahagian GA.
  17. Diabetes Care. 1998 Aug;21(8):1322-5.Diabetic peripheral neuropathy. Effectiveness of electrotherapy and amitriptyline for symptomatic relief. Kumar D, Alvaro MS, Julka IS, Marshall HJ.
  18. Amitriptyline vs. pregabalin in painful diabetic neuropathy: a randomized double blind clinical trial Diabet. Med. 26, 1019–1026 (2009). D. Bansal, A. Bhansali*, D. Hota, A. Chakrabarti and P. Dutta
  19. A Comparison of Amitriptyline and Maprotiline in the Treatment of Painful Polyneuropathy in Diabetics and Nondiabetics.Clinical Journal of Pain December 1997; 13(4) 313-323; Vrethem, Magnus; Boivie, Jörgen; Arnqvist, Hans M.D.; Holmgren, Helen M; Lindström, Torbjörn M.D.; Thorell, Lars-Håkan
  20. Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy;Diabet. Med. 24, 377–383 (2007) V. M. Jose, A. Bhansali, D. Hota and P. Pandhi
  21. Diabetes Care. 2011 Apr;34(4):818-22.A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: a randomized, double-blind, cross-over clinical trial. Kaur H, Hota D, Bhansali A, Dutta P, Bansal D, Chakrabarti A.
  22. Pain. 2004 Aug;110(3):697-706. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study.Rowbotham MC, Goli V, Kunz NR, Lei D.
  23. Pharmacol Rep. 2012 Sep;64(5):1267-75. Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model. Cegielska-Perun K, Bujalska-Zadrożny M, Makulska-Nowak HE.
  24. Clinical Pharmacology and Therapeutics (1992) 52, 547–552; The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. Søren H Sindrup MD, Ulla Bjerre MD, Anders Dejgaard MD, Kim Brøsen MD, Tove Aaes-Jørgensen MSc and Lars F Gram, R. Quibrera, H. González-Millán and O. Lozano Castañeda
  25. Gabapentin for the treatment of painful diabetic neuropathy: dosing to achieve optimal clinical response Br J Diabetes Vasc Dis 2004;4:173–8. Francisco J Gómez-Pérez, Armando Perez-Monteverde, Osvaldo Nascimento, Pablo Aschner, Marino Tagle, Klaus Fichtner, Ponni Subbiah, Elizabeth M Mutisya
  26. Neurology. 2004 Dec 14;63(11):2104-10.Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Lesser H, Sharma U, LaMoreaux L, Poole RM.
  27. Indian J Pharmacol. 2012 Jan;44(1):51-6. Evaluation of efficacy and safety of gabapentin, duloxetine, and pregabalin in patients with painful diabetic peripheral neuropathy. Devi P, Madhu K, Ganapathy B, Sarma G, John L, Kulkarni C.
  28. Neurology. 2006 Nov 28;67(10):1792-800.Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK.
  29. Pain 2005 Jul;116(1-2):109-18, Duloxetine vs. placebo in patients with painful diabetic neuropathy, Goldstein DJ et al
  30. Diabetologia Volume 5, Number 4 (1969), 215-218,Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine (Tegretol®): Double blind crossover trial. J. A. Rull, R. Quibrera, H. González-Millán and O. Lozano Castañeda
  31. Neurology. 1998 Jun;50(6):1842-6. Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P,Cornblath D, Sachdeo R, Siu CO, Kamin M.
  32. Current Medical Research & Opinion Vol. 27, No. 1, 2011, 151–162. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial Sherwyn Schwartz, Mila Etropolski, Douglas Y. Shapiro, Akiko Okamoto, Robert Lange, Juergen Haeussler, Christine Rauschkolb
  33. Pain. 2003 Sep;105(1-2):71-8. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Watson CP, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J.
  34. Neurology. 2003 Mar 25;60(6):927-34. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Gimbel JS, Richards P, Portenoy RK.
  35. Diabetes Care. 2005 Feb;28(2):485-7. Use of methadone for the treatment of diabetic neuropathy. Hays L, Reid C, Doran M, Geary K.
  36. Cohen KL, Harris S. Efficacy and safety of nonsteroidal antiinflammatory drugs in the therapy of diabetic neuropathy. Arch Intern Med. 1987;147:1442-1444.
  37. Diabetologia. 1995 Dec;38(12):1425-33. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schütte K, Gries FA.
  38. Diabetes Care. 1999 Aug;22(8):1296-301.Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schütte K, Kerum G
  39. Gerritje S. Mijnhout, Boudewijn J. Kollen, Alaa Alkhalaf, Nanno Kleefstra, and Henk J. G. Bilo, “Alpha Lipoic Acid for Symptomatic Peripheral Neuropathy in Patients with Diabetes: A Meta-Analysis of Randomized Controlled Trials,” International Journal of Endocrinology, vol. 2012, Article ID 456279, 8 pages, 2012. doi:10.1155/2012/456279
  40. D. Ziegler, P. A. Low, and W. J. Litchy, “Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial,” Diabetes Care,vol. 34, pp. 2054–2060, 2011.
  41. Diabetes Care. 1992 Nov;15(11):1550-5. Mexiletine in the treatment of diabetic neuropathy. Stracke H, Meyer UE, Schumacher HE, Federlin K.
  42. The Lancet 331, Issues 8575–8576, 9 January 1988, 9–11. MEXILETINE FOR TREATMENT OF CHRONIC PAINFUL DIABETIC NEUROPATHY. Anders Dejgarda, Palle Petersenb, Jens Kastrupc
  43. Neurology. 2004 Sep 14;63(5):865-73. Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects. Raskin P, Donofrio PD, Rosenthal NR, Hewitt DJ, Jordan DM, Xiang J, Vinik AI
  44. Neurology May 1, 1997 vol. 48 no. 5 1212-1218. High dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Kristine A. Nelson, Karen M. Park, Elaine Robinovitz, Constantine Tsigos, and Mitchell B. Max
  45. Neurology. 2001 Aug 14;57(3):505-9.Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Eisenberg E, Lurie Y, Braker C, Daoud D, Ishay A.
  46. Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy;Diabet. Med. 24, 377–383 (2007) V. M. Jose, A. Bhansali, D. Hota and P. Pandhi
  47. QJM. 2004 Jan;97(1):33-8. Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study. Kochar DK
  48. Pain Pract. 2012 Nov 27. in press. A Randomized, Controlled Trial of Gabapentin Enacarbil in Subjects with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy.Rauck R, Makumi CW, Schwartz S, Graff O, Meno-Tetang G, Bell CF, Kavanagh ST, McClung CL.
  49. Diabetes Care 25:1699–1703, 2002 Treatment of Chronic Painful Diabetic Neuropathy With Isosorbide Dinitrate Spray A double-blind placebo-controlled cross-over study. KEVIN C.J. YUEN, NEIL R. BAKER, GERRY RAYMAN
  50. Glyceryl Trinitrate Patches as an Alternative to Isosorbide Dinitrate Spray in the Treatment of Chronic Painful Diabetic Neuropathy. DIABETES CARE, VOLUME 26, NUMBER 9, SEPTEMBER 2003; 2697-8. GERRY RAYMAN, NEIL R. BAKER, SINGHAN T.M. KRISHNAN
  51. Application of OpSite Film: a New and Effective Treatment of Painful Diabetic Neuropathy Diabetic Medicine Volume 11, Issue 8, pages 768–772, October 1994 Mrs. A.V.M. Foster*, C. Eaton, D.O. McConville, M.E. Edmonds
  52. The use of Opsite, Fixomull and Lycra ® in the management of diabetic neuropathic pain of the foot. Primary Intention 2002; 10(4):162-164, 166-170.Troy T.
  53. Diabetes Care. 2000 Mar;23(3):365-70.Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain. Hamza MA, White PF, Craig WF, Ghoname ES, Ahmed HE, Proctor TJ, Noe CE, Vakharia AS, Gajraj N.
  54. Pain Manag Nurs. 2012 Sep;13(3):150-6. doi: 10.1016/j.pmn.2009.08.001. Postoperative pain: acupuncture versus percutaneous electrical nerve stimulation. Gavronsky S, Koeniger-Donohue R, Steller J, Hawkins JW.
  55. Endocr Pract. 2007 Jul-Aug;13(4):355-62.Prevalence of sleep apnea in a population of adults with type 2 diabetes mellitus. Einhorn D, Stewart DA, Erman MK, Gordon N, Philis-Tsimikas A, Casal E.
  56. Am J Respir Crit Care Med. 2012 Sep 1;186(5):434-41.Obstructive sleep apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes.Tahrani AA, Ali A, Raymond NT, Begum S, Dubb K, Mughal S, Jose B, Piya MK,Barnett AH, Stevens MJ.
  57. A RANDOMIZED SHAM-CONTROLLED TRIAL OF SCIATIC NERVE NEURODYNAMIC MOBILIZATION IN PAINFUL DIABETIC PERIPHERAL NEUROPATHY P. S. Kumar1, P. Adhikari2, M. M. Prabhu. IASP Poster PH 479, Montreal 2010
  58. Study of wax therapy on diabetic peripheral neuropathy. Wen Huijun,Yang Jinsuo,Zhang Jianjun,Wei Xiaoli. Modern Journal of Integrated Traditional Chinese and Western Medicine 2008-35
  59. D. Kumar, H.J. Marshall, Diabetic peripheral neuropathy:amelioration of pain with transcutaneouselectrostimulation, Diabetes Care 20 (1997) 1702–1705.
  60. The Comparison of Effectiveness of TENS and Placebo TENS in Peripheral Neuropathic Pain in Patients with Type II Diabetes Mellitus Turkiye Klinikleri J Med Sci 2011;31(4):913-8. Meltem BULUT, Ayşe ÖZCAN, Türkay ÇAKAN, Meltem BEKTAŞ, Cavit ÇULHA
  61. Somers DL, Somers MF. Treatment of neuropathic pain in a patient with diabetic neuropathy using transcutaneous electrical nerve stimulation applied to the skin of the lumbar region. Phys Ther 1999;79(8):767-75.
  62. The Journal of Foot & Ankle Surgery 37(3) :191-194, 1998. Beneficial Effects of Electrical Stimulation on Neuropathic Symptoms in Diabetes Patients Inderjeet Singh Julka, MD, Michael Alvaro, DPM, and Dinesh Kumar
  63. Diabet Med. 2004 Aug;21(8):940-4.Electrical stimulation therapy through stocking electrodes for painful diabetic neuropathy: a double blind, controlled crossover study.Oyibo SO, Breislin K, Boulton AJ.
  64. Neuropharmacology. 2010 Mar;58(3):585-92. Functional and biochemical evidence indicating beneficial effect of Melatonin and Nicotinamide alone and in combination in experimental diabetic neuropathy. Negi G, Kumar A, Kaundal RK, Gulati A, Sharma SS.
  65. Formulations of magnesium compounds for local application and methods of treatment using the same. AJ Marx - US Patent 5,898,037, 1999