The most common presentation is that of a bilateral painful peripheral neuropathy. However, pain can also be unilateral, when it is usually secondary to a focal neuropathy or mononeuritis.
Peripheral painful neuropathy
This is a singularly disagreeable complication of diabetes. Patients in severe pain who cannot sleep become profoundly disturbed, confused, depressed and unwell. Relentless, burning pain and contact dysaesthesia make patients extremely miserable. It is particularly difficult to bear because apart from the pain there are often no signs which make it obvious that something is wrong. Some patients have described severe painful neuropathy after starting insulin, a so-called insulin neuritis, but the symptoms gradually improve if tight control is maintained.
Some health-care practitioners are unsympathetic because of the absence of signs.
The pain may be sharp, shooting, stabbing or burning. There may be paraesthesiae or deep muscular aching pain, restless legs, cramps and/or sensation of cold.
Distribution of pain is usually in both feet extending into the lower legs in a stocking distribution. One limb may be slightly worse than the other. However, unilateral pain suggests either a diabetic mononeuropathy, such as femoral neuropathy, or nerve root pain due to compression such as in a prolapsed intervertebral disc.
Painful neuropathy is worse in bed at night, and when the feet and legs are in contact with clothes, including bedclothes.
On examination the feet and legs may be normal, although some patients may show a stocking distribution of loss of sensation. There may be an increased sensation to a normal stimulus such as light touch and this is termed allodynia or contact hypersensitivity. When there is increased sensation to normal painful stimuli such as pinprick, this is referred to as hyperalgesia.
When the pain is unilateral it is important to look for focal signs of root or nerve pathology, for example focal muscular weakness or unilateral loss of reflexes.
It is important to distinguish painful neuropathy from ischaemic rest pain. Rest pain is relieved by dependency but painful neuropathy is not affected by position change. In limbs with painful neuropathy, pulses are usually present. However, in the limb with rest pain there are definite signs of ischaemia, with absent pulses.
Patients suspected of having peripheral painful neuropathy should have:
• Full blood count
• Liver function tests
• Protein electrophoresis
Other causes of painful neuropathy include B12 deficiency, renal failure, alcoholic neuropathy associated with liver dysfunction and myeloma.
Vascular investigations should be carried out to rule out an ischaemic cause of the pain. In painful neuropathy, transcutaneous oxygen tension is greater than 30 mmHg and in the ischaemic limb, transcutaneous oxygen tension is usually less than 30 mmHg.
The first important step is to reassure the patient that he will get better. Painful neuropathy nearly always resolves within 2 years although the pain may be replaced by numbness. The patient should be told that there is no danger of amputation.
The next step is to explore the many treatment options and try to find something to tide the patient over the next months before the pain resolves. If one treatment does not work there will be others to be tried. Reassurance, sympathy and tender loving care alone will help considerably: the knowledge that the pain will not last forever and that every attempt will be made to relieve it are also helpful. Frequent appointments should be made for review and assessment so that patients do not feel abandoned. If the patient can be helped to sleep he will feel better.
Simple measures may help. Pain may be relieved by cold: a basin of cool water may be kept beside the bed. One of our patients purchased a small refrigerator, kept it at the end of the bed, and inserted his feet when woken by pain! One patient wore a pair of his wife's tights under his
trousers: another patient wore silk pyjamas underneath his city suit. A bed cradle can be used to prevent the bedclothes from touching the lower limb.
Treatment can be divided into four modalities:
• Topical therapy
• Glycaemic control
• Physical treatment.
OpSite film stuck directly onto the skin and OpSite spray may help to relieve burning pain and contact dysaesthesia (Fig. 3.11).
Capsaicin is applied as a cream, and depletes peripheral pain fibres of substance P thereby blocking transmission of painful signals from the periphery to central neurones. It should be applied sparingly in a thin layer four times daily to the affected area. It should only be used on intact skin. Burning or tingling may occur in the first 2 weeks but the patient should be encouraged to persist. Patients should wash their hands immediately after use. The analgesic effect may take 6 weeks to develop.
Hyperglycaemia is known to lower the threshold to pain and in general diabetic control is usually poor in patients with painful neuropathy. It is important to improve con trol. In patients with type 2 diabetes, oral hypoglycaemic therapy should be optimized, but if this fails then insulin therapy should be started.
This consists of analgesics, hypnotics, tricyclic antidepressants, anticonvulsants and antiarrythmics.
Analgesics. Initial therapy should be simple analgesics such as aspirin or paracetamol. If necessary, stronger analgesics maybe given, such as dihydrocodeine or tramadol.
Hypnotics. Hypnotics are extremely helpful as loss of sleep makes the patient more sensitive to pain and induces depression.
Tricyclic antidepressants. Imipramine or amitriptyline may relieve burning pain. It is best to commence at a low dosage at night to avoid the side-effect of postural hypotension. The dose of amitriptyline should be 25 mg initially and this should be increased to 150 mg over a period of 16-20 weeks as long as serious side-effects do not occur. Mild side-effects include drowsiness, constipation, blurred vision, dry mouth and sweating. However, these symptoms should not persist on continuing therapy. If they do, the dose should be reduced. If the patient has difficulty in passing urine or becomes confused or develops palpitations then the medication should be stopped immediately by the patient, who should be reviewed urgently.
Anticonvulsants. These include gabapentin, phenytoin, carbamezapine, sodium valproate and lamotrigine. Gabapentin is commonly used and the starting dose is 300 mg on the first day, 600 mg on the second and 900 mg on the third day. Thereafter the dose should be increased to 1800 mg daily. It is usually well tolerated and initial drowsiness resolves.
Carbamezepine can be started at 100 mg once or twice daily and increased up to the maximum tolerated dosage (usually 800-1000 mg/day). Valproate (100-500 mg 1-3 times daily) and phenytoin (100-400 mg 1-2 times daily) maybe helpful.
Lidocaine can be given by intermittent intravenous infusion and may provide relief for several days. Mexilet-ine often has unacceptable side-effects although dosages of 450 mg/day significantly reduce burning pain and paraesthesiae without causing cardiovascular side-effects. Anecdotally, patients have reported that cannabis helps.
Transcutaneous electrical nerve stimulation (TENS) can be used to block the pain. Electrodes are placed on either side of the painful area. Acupuncture has anecdotally been reported as useful. In very severe cases, spinal cord stimulation with implanted spinal electrodes has been used.
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