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Diabetic peripheral neuropathic pain

Diabetic neuropathic pain is the most common presentation of diabetic polyneuropathy. Diabetic polyneuropathy is found in 50% of people with long duration of diabetes (those who were diagnosed with the condition more than 15 years ago).1

There have been many small-scale studies showing varying degree of prevalence of diabetic peripheral neuropathic pain (DPNP), ranging from 16% to 26%.2,3 This differing research sampling and diagnostic criteria, such as duration of diabetes, can help explain these differences in range. In 2011, a large community-based study of 15,692 people with diabetes in North West England, conducted over a four-year period, showed one-third of all diabetic patients have DPNP.4 This study also noted greater pain levels in women, as well as in people with type 2 diabetes and people of South Asian origin. 

Diabetic neuropathy is the name given to long-term damage to the nerve fibres. Peripheral neuropathy is bilateral damage to the nerves of limbs, especially feet. A widely accepted definition of diabetic peripheral neuropathy is, “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after exclusion of other causes.”5 The other causes being hypothyroidism, alcoholism and vitamin B12 deficiency (it is important to rule out vitamin B12 deficiency related to metformin or a vegetarian diet).

 

Symptoms of DPNP

Symptoms on DPNP are common in the feet and lower legs. However, in severe cases pain may also occur in the fingers and hands. This pain can be constant or recurrent in nature but is often reported to be worse at night as patients become more sensitive to temperature changes and touch. Patients may have a heightened sensitivity to very light touch (allodynia), report sharp responses to touch (hyperaesthesia) and often pull away during foot examination due to oversensitivity.5

DPNP can last for years and impair quality of life, in contrast to acute sensory neuropathy (ASN) which occurs when there are sudden changes in glycaemic status, for example in insulin neuritis, that will gradually improve when glycaemic control is stabilised, and will often resolve within 12 months.6

Patients with neuropathic foot will also be insensitive to pressure, pain and temperature differences, so minor injuries or rubbing from footwear can quite quickly lead to diabetic foot ulceration.7 They also have loss of reflexes and muscle weakness, leading to balance, co-ordination and gait changes. 

 

Quality of life issues

Painful neuropathy can cause severe physical and mental dysfunction as well as sleep disturbance.8 In patients with confirmed DPNP, symptoms have been shown to adversely effect the quality of life in areas such as sleep disruption, which left untreated can lead to depression.9 A small study in Wales showed DPNP was more likely to occur with increasing neuropathy.3 

Pain is a complex emotion and is reliant on patients' mental, emotional and educational knowledge. Neuropathy can cause emotional stress leading to pain, depression, neuropathic symptoms and unsteadiness.8 For many patients, this can severely restrict their daily lives and therefore clinicians should carefully assess patients, explain the diagnosis of DPNP and devise a patient management plan which includes realistic treatment goals. Patients will need substantial reassurance during this difficult period as to how they can improve their daily lives, as being unable to manage their symptoms will continue to cause increased anxiety.  

 

Causes of DPNP

The exact mechanism of cause of DPNP is not well understood. However it is clear that changes in glycaemic control relate to metabolic abnormalities in nerve tissue.10 Abnormalities in blood supply to the nerves leads to nervous tissue being deprived of oxygen, and both factors contribute to the longest and shortest nerves (both myelinated and demyelinated fibres) being affected. Diabetic neuropathy is found in people who have a long duration of diabetes1 and those who have problems controlling their blood glucose levels. The UK Prospective Diabetes Study (UKPDS) found that 7% of all newly-diagnosed patients with type 2 diabetes, aged between 25 to 65 years, had evidence of neuropathy. Painful neuropathy can also be induced by intense rapid improvements in glycaemic control.11

 

Diagnosis of DPNP

In practice the diagnosis of PDNP relies on the patient's history and their own account and difficulty in describing their symptoms. Patients often use a range of explanations to highlight pain and distress which include tingling, burning symptoms, 'walking on pebbles', sudden sharp stabbing pains, pain shooting through feet often described as electric shock type pain.12 

However not all patients report pain, and some will only focus on sensory loss.13 In some cases, patients will not make the 'pain' connection due to sensory loss, particularly if there is no apparent external cause.14

There are a variety of validated tools currently available to diagnose neuropathic pain, however there is no national consensus as to which tool is best. Most professionals use a combination of tools that include pain scores, verbal description and neurological testing. The most commonly used are the Neuropathic Pain Questionnaire (NPQ) and the Leeds Assessment of Neuropathic Symptoms (LANSS). Some clinics use a simple measure and ask patients to rate pain from zero to ten, with a score of zero being pain-free and ten being in tremendous pain. There is also a visual tool, developed by Lilly, which incorporates a series of easy to read pictures to aid communication between patient and clinician to represent different pain, for example burning and tingling.13 

The diabetes Quality and Outcomes Framework (QOF) requires GP practices to allocate a risk category to patients, based on foot inspection and foot examination of pulses and neuropathy testing using a 10g monofilament. However QOF does not specifically reward practices for treating DPNP nor does it promote referral to a specialist foot specialist team, unless patients require further specialist input. The examination itself helps to address risk factors and patients are more likely to mention neuropathic symptoms at this stage. Practice nurses are ideally placed to provide appropriate advice and management on basic foot care and risk management.

Patients should be encouraged to describe their individual symptoms without too many leading questions from the clinician. Painful diabetic neuropathy can result in reduction in sleep as well as general and social activity, which in turn impacts on the quality and enjoyment of life. It has also been associated with increased anxiety and depression levels, and in a worst case scenario can even lead to unemployment.15

 

Improving and treating DPNP 

DPNP can be treated using NICE Guideline 96, Management of Neuropathic Pain, which provides a specific management pathway for treating painful diabetic neuropathy. It is always important to carefully listen to the patient concerns and discuss any coping mechanisms that the patient might find useful to manage their pain.  

Current recommended therapies only offer up to about 50% pain relief16 therefore it is essential to discuss the current treatment options available (including any possible side effects) and clarify that there will not necessarily be a complete reduction in pain and suggest how pain might be improved and managed through dose titration of the pertinent oral therapies. 

It is also important to highlight the importance of good blood glucose control and the need to improve any other pre-existing cardiovascular risk factors such as hypertension, hyperlipidaemia, obesity and smoking, through the implementation of appropriate lifestyle measures.17

 

In practice

In practice, patients will often discuss the neuropathic symptoms they are most worried about through answers to open-ended questions. Patients are advised to try and avoid having large fluctuations in their blood glucose levels and are informed about the importance of implementing general lifestyle changes into their daily lives, including exercise, before any pharmacological treatments are discussed. 

By the end of the first visit, a management plan which has been discussed and agreed with the patient will have been developed, which should exercise - for example walking 30 minutes daily and exercising their feet by counting each turn of the ankle before bedtime, starting with five and adding a further turns as appropriate. Patients have found this useful in early diagnosis when there is no pain as yet but the patient has started to feel discomfort.

Treatments recommended by NICE are outlined in Box 1. There are also topical treatments such as capsaicin and lidocaine patches available. Both have had small trials undertaken but have been shown to be of little benefit, with side-effects such as skin irritations reported. NICE doesn't recommend any topical treatments, but anecdotally some patients report that simply massaging simple emollients onto the skin can have a soothing effect. 

Acupuncture is also available and small studies have shown improvements in pain relief, sleep and the wellbeing of patient's quality of life.18,19 

 

References

1. Dyck PJ, Kratz KM, Karnes JL, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 1993;43:817-24.

2. Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med 2004;21:976-82.

3. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006;29:1518-22.

4. Abbott CA et al. 2011 Prevalence and Characteristics of Painful Diabetic Neuropathy in Large Community-Based Diabetic Population in the UK. Diabetes Care 2011;34(10):2220-2224. 

5. Boulton AJ, Malik RA. Diabetic neuropathy, Med Clin North Am 1998;82(4):909-2.

6. Caravati CM. Insulin neuritis a case report. Va Med Mon 1933;59:

745-746.

7. Reiber GE et al. Causal pathways for incident lower-extremity ulcers in patients with diabetes form two settings. Diabetes Care 1999;22:

157-162.

8. Vileikyte et al. Diabetic Peripheral neuropathy and depressive symptoms: the association revisited Diab Care 2005;28:2378-2383.

9. Argoff CE et al. Diabetic peripheral neuropathic pain: clinical and quality-of-life issues. Mayo Clinic Proc 2006:81(4s Suppl):S3-11.

10. Cameron NE, et al 2001: Vascular factors and metabolic interactions in pathogenesis of diabetic neuropathy. Diabetologia 44:1973-88.

11. Llewelyn JG et al Acute painful diabetic neuropathy precipitated by strict glycemic control. Acta Neuropathol 1986:72:157-63.

12. Edmonds et al. A Practical Manual of Diabetic Foot Care. Oxford: Blackwell Publishing; 2005.

13. Malik R et al. Addressing the burden of diabetic peripheral neuropathic pain supplement. Diabetic Foot Journal 2010;13:4.

14. Lillirank A. Back pain and the resolution of diagnostic uncertainty in illness narratives. Soc Sci Med 2003;57:1045-54.

15. Nicholson B, Verma S. Comorbidities in chronic neuropathic pain. Pain Med 2004:5(suppl 1):S9-S27

16. Sultan et al. Duloxetine for painful diabetic neuropathy and fibromyalgia pain systematic review of randomised trials. BMC Neurology 2008,8:29.

17. Tesfaye S, Chaturvedi N, Eaton SEM, et al. Vascular risk factors and diabetic neuropathy. New Engl J Med 2005;352:341-50.

18. Green J, McClennon J. Diabetic Foot Journal 2006;9:4. 

19. Walker S. A nurse led acupuncture service for painful diabetic neuropathy. Journal of Diabetes Nursing 2001;5:2.