Management of Diabetic Painful Neuropathy


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The Goal of treatment of Diabetic Painful Neuropathy include

  1. Good glycemic control
  2. Symptomatic relief
  3. Halt progression of nerve fibre loss


DCCT Research Group showed that improved control of glucose reduces the risk of clinically meaningful Neuropathy 60% (p ≤ .002), Retinopathy 76% (p ≤ .002) and Nephropathy 54% (p ≤ .04).

First line medication include: - Tricyclic anti-depressants, Duloxetine, Gabapentin, Pregabalin, Opiod analgesics and Tramadol

Gabapentin [α-2-delta voltage gated calcium- channel antagonist]. 

Begin at low dose; 100-300 mg taken at bedtime. Gradually increase dose by 100-300 mg weekly as tolerated. Maximum dose is 3600 mg/day which is rarely reached my experience. Give the patient 1-2 weeks for titration of dose. Patience is needed; rapid dose escalation may result in undue drowsiness. Use lower doses in patients with renal impairment. Concomitant use of antacids may reduce bioavailability of Gabapentin. Major side effects include sedation, ataxia and nystagmus; these are rare.

Pregabalin [α-2-delta voltage gated calcium- channel pathway moderator].   It is an analogue of Gabapentin but with higher Ca++ channel affinity and better bioavailability. Start medication at low dose of 50-150 mg a day divided in 8-12 hourly doses. Increase dose weekly by 50-150 mg/ day. Maximum dose is 300-600 mg/day in divided doses. Caution is needed in renal impairment. Side effects include sedation, dry mouth and rarely ataxia. 

Tricyclic antidepressants (TCAs):

Start at low doses of 10-25 mg.  Increase doses by 10-25 mg every

3 to 7 days. Maximum doe is 300-400 mg per day in divided doses; however, this dose is very high and

rarely achieved in clinical practice. Care must be taken with the elderly and those with heart disease as it may result in urine retention and arrhythmias. Give the patient 6-8 weeks trial period with 1-2 weeks at peak dose for maximal effect to be achieved. Side effects include hypertension, sedation, dry mouth, urine retention and arrhythmias.

Duloxetine:  Selective serotonin nor-epinephrine reuptake inhibitors (SNRIs) such as Duloxetine and Venlafaxine have been shown to be effective in relieving neuropathic pain by increasing the synaptic availability of 5-HT and nor-epinephrine in the descending pathways that inhibit pain impulses.

Start low dose of 30 mg taken at night; gradually increase to 60-120 mg in divided doses.

Opiod analgesics [Tramadol, Morphine]

Tramadol: Tramadol is a centrally acting weak Opiod and a mixed serotonin Nor-epinephrine          re-uptake inhibitor.  Start at low dose of 50 mg once or twice a day.  Increase the dose by 50-100 mg a day in divided doses, every 3-7 days.  Maximum dose is 300-400 mg a day in 3-4 divided doses.   Use Tramadol with caution in patients with epilepsy because it lowers seizure threshold.  Give the patient up to 4 weeks trial at maximal dose to evaluate response. 

Morphine sulphate: Before starting morphine, screen the patient for alcohol abuse. Start at low dose of 15 mg. every four to six hours as needed. Concomitant use of stool laxatives is advocated. In the past there has been a lot of reluctance to use morphine even in deserving cases, this should not be so.

Capsaicin: Capsaicin is an ingredient of hot chili peppers. Substance P, a neuropeptide is released from pain fibers in response to trauma. Its application on the skin results in depletion of substance P from sensory nerves in the skin hence relieving pain.  It is applied locally over the affected areas.

Non – pharmacological modes of management

Non-pharmacological modes of management of neuropathic pain include trans-cutaneous electrical nerve stimulation, physiotherapy, behavioral therapy and counseling. None of these, however, have undergone rigorous randomized controlled trials to prove efficacy.


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