|ORIGINAL RESEARCH REPORT
|Year : 2016 | Volume
| Issue : 2 | Page : 46-50
Frequency of neuropathic pain in type 2 diabetes mellitus at the Lagos University Teaching Hospital: A questionnaire-based outpatient survey
Oluwadamilola O Ojo1, Ifedayo A Odeniyi2, Sandra O Iwuala2, Olajumoke O Oshinaike3, Njideka U Okubadejo1, Olufemi A Fasanmade2
1 Department of Medicine, Neurology Unit, College of Medicine, University of Lagos, Lagos, Nigeria
2 Department of Medicine, Endocrinology and Metabolism Unit, College of Medicine, University of Lagos, Lagos, Nigeria
3 Department of Medicine, Neurology Unit, College of Medicine, Lagos State University, Lagos, Nigeria
|Date of Web Publication||4-Apr-2016|
Oluwadamilola O Ojo
Department of Medicine, Neurology Unit, College of Medicine, University of Lagos, PMB 120003, Idi Araba, Lagos
Source of Support: None, Conflict of Interest: None
Background: Neuropathic pain (NP) is one of the most common complications of type 2 diabetes mellitus (DM). The frequency of NP in population living with type 2 DM is unclear. Objective: To determine the frequency of NP symptoms in patients with type 2 DM. Materials and Methods: This cross-sectional study recruited 250 type 2 DM patients attending the outpatient diabetes clinic of the Lagos University Teaching Hospital (LUTH) over a period of 4 weeks. Demographic data and data regarding current DM treatment, prior diagnosis of NP, and current treatment of NP were obtained using a structured questionnaire. Glycaemic status of the patients was assessed measuring fasting blood glucose and glycosylated hemoglobin level. Presence of NP was documented using the painDETECT questionnaire (PDQ). Results: NP was present in 54 out of the 250 type 2 DM patients studied giving a frequency of 21.6%. Out of 54 patients 36 (66.7%) were females and 18 (33.3%) were males giving a male: female ratio of 1:2 (P < 0.05). The mean age of type 2 DM patients with NP was significantly higher than the mean age of type 2 DM patients without NP (62.4 ± 10.9 years vs 58.9 ± 11.7 years; P = 0.05). Glycaemic status and disease duration did not differ among DM patients with or without NP. Only 10 out of 54 (18.5%) patients were treatment naοve at the time of study; however, out of the 44 patients receiving treatment only 9 (20.5%) were on appropriate treatment compared to international guidelines on treatment of diabetic NP. Conclusion: NP was present in 21.6% of type 2 DM patients attending the LUTH.
Keywords: Lagos University Teaching Hospital, neuropathic pain, treatment, type 2 diabetes mellitus
|How to cite this article:|
Ojo OO, Odeniyi IA, Iwuala SO, Oshinaike OO, Okubadejo NU, Fasanmade OA. Frequency of neuropathic pain in type 2 diabetes mellitus at the Lagos University Teaching Hospital: A questionnaire-based outpatient survey. J Clin Sci 2016;13:46-50
|How to cite this URL:|
Ojo OO, Odeniyi IA, Iwuala SO, Oshinaike OO, Okubadejo NU, Fasanmade OA. Frequency of neuropathic pain in type 2 diabetes mellitus at the Lagos University Teaching Hospital: A questionnaire-based outpatient survey. J Clin Sci [serial online] 2016 [cited 2019 Aug 19];13:46-50. Available from: http://www.jcsjournal.org/text.asp?2016/13/2/46/179648
| Introduction|| |
Neuropathic pain (NP) is defined as pain resulting from damage to the peripheral or central somatosensory system. , It is associated with considerable disability including functional impairment and psychosocial dysfunction.  The causes of NP include painful diabetic neuropathy (PDN), postherpetic neuralgia, painful nondiabetic small fiber neuropathy, entrapment neuropathies, and radiculopathies. The most common cause of peripheral neuropathy worldwide, Nigeria inclusive, is diabetes mellitus (DM) and PDN is the most common neurologic complication of type 2 diabetes.  Overall, approximately 10% of patients with diabetes experience persistent pain from distal symmetric polyneuropathy (DSP)  and approximately 20% of them experience pain that is severe enough to result in significant amount of impairment in motor functioning and quality of life. 
PDN is the presence or occurrence of NP in patients with DM. Though there is considerable evidence regarding the pathophysiologic mechanisms causing nerve damage in DM, they do not distinguish between painless and painful DM neuropathy. The following mechanisms have been proposed to result in altered pain transmission leading to PDN  : Spinal rewiring (sprouting of A-fibers), , peripheral sensitization leading to central spinal sensitization, , ectopic electrical impulses,  metabolic changes such as rapid changes/fluctuation in blood glucose, , and sorbitol accumulation in the nerves from activation of the polyol pathway. 
Clinical features of DSP comprise both "positive" and "negative" symptoms and may be asymptomatic. Positive symptoms include abnormal excessive sensations such as burning, pricking, or tingling, and these positive symptoms result in NP. The negative symptoms such as numbness or sensory loss are sometimes severe enough to lead to painless injuries.
Diabetic pain syndromes can be classified according to its duration.  Those that occur for less than 6 months are classified as acute. These include a self-limiting syndrome such as insulin neuritis syndrome that occurs often at the beginning of therapy for diabetes. Pain syndromes continuing longer than 6 months are classified as chronic.  The pain may be ongoing, spontaneous, or hyperalgesic (increased response to a painful stimulus). NP in DM is usually severe and sometimes intractable.
The diagnostic evaluation of NP in DM (just like NP from any other etiology) requires a concise clinical history, physical examination, and confirmatory investigations. Clinical features suggestive of NP are presence of positive phenomenon described above in the presence of sensory loss. The most common confirmatory tests are nerve conduction studies (NCSs), and the most common feature found is reduction in the sensory nerve action potential amplitudes of lower extremities. Other tests such as skin biopsy with measurement of intraepidermal nerve fiber density can be used in patients with suspected small fiber neuropathy with normal NCSs.
Surveys have shown that nearly 25-39% of diabetes patients with NP are either undiagnosed, and therefore, untreated or poorly treated with minimal control of pain. ,, The associated discomfort continues to interfere considerably with sleep, daily functioning, and other aspects of quality of life. 
Several studies have reported the prevalence of NP in patients with type 2 DM. However, reports vary as the methodology and case definition differ from study-to-study. Historically, the prevalence of PDN ranges 10-20% of the diabetic population and 40-50% of the diabetic patients with peripheral neuropathy. ,,,
In a review of the epidemiology of PDN, the prevalence was estimated as 15% in the diabetic population.  There are several reports in our environment on peripheral neuropathy in patients with DM; however, studies addressing NP are usually sparse hence the need for this study.
Our aim was to determine the frequency of NP symptoms in type 2 DM patients from an outpatient perspective and also to determine the proportion of these that are on treatment.
| Materials and methods|| |
Approval of the study protocol was obtained from the Health Research and Ethics Committee of the Lagos University Teaching Hospital (LUTH). The study was cross-sectional and descriptive in nature and conducted at the outpatients diabetes clinic of the LUTH. All consecutively attending persons with type 2 DM over a 4-week period were recruited after obtaining informed consent from them.
The study instrument incorporated the PainDETECT questionnaire (PDQ) along with demographic data, and questions regarding current DM treatment, prior diagnosis of NP, and current treatment of NP where relevant. Glycaemic status was assessed using fasting plasma glucose and glycosylated hemoglobin level. The PDQ is a simple screening tool designed to detect NP symptomatology in patients with pain. The total score on the pain questionnaire is graded as follows: 0-12 (negative: NP component is unlikely), 13-18 (unclear: result is ambiguous; however, an NP component may be present), and 19-38 (positive: an NP component is likely).
The instrument was interviewer administered, with additional information obtained from case records at the time of the interview. All information was based on historical data.
NP was defined as pain arising as direct consequence of a lesion or disease affecting the somatosensory system for the purpose of the study. Pain restricted to the joints was classified as somatic/nociceptive pain (probable osteoarthritis).
Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 20.0 (SPSS-Inc., Chicago, US).
| Results|| |
A total of 250 type 2 DM patients were recruited for the study from the diabetic clinic of the LUTH. The study subjects comprised 96 males and 154 females. The demographic parameters (age, sex ratio) and DM-related characteristics (mean duration of diabetes, body mass index, mean indices of glycaemic control) are shown in [Table 1]. Out of all the subjects, 58.6% had long-duration diabetes (defined as diagnosis of DM >5 years).
|Table 1: The demographic and treatment-related characteristics of the study population|
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All study subjects were on treatment for DM. Out of these subjects, 65.6% were on a combination of sulfonylureas and biguanides; 9.6% were on biguanides only; 8.8% were on insulin only; 4.8% were on a combination of sulfonylureas, biguanides, and thiazolidinediones; 4% were on insulin and biguanides; 2.8% were on sulfonylurea only. Insulin with sulfonylureas was used by 0.8% of the study subjects.
Frequency and characteristics of NP symptoms
Out of 250 study subjects, 99 (39.6%) experienced pain as per the PDQ. The distribution of the different types of pain is shown in [Figure 1].
|Figure 1: Distribution of pain syndromes using the PainDETECT questionnaire|
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Out of the 99 patients, 54 who reported pain were likely to have NP making the frequency of PDN in our type 2 DM patients 21.6%. Out of all the subjects, 36 (66.7%) were females and 18 (33.3%) were males giving a male: female ratio of 1:2 (χ2 = 11.9, P < 0.05).
Pattern of NP using the PDQ
Of the 54 type 2 DM patients with NP symptomatology, 17 (31.5%) experienced pain attacks with pain in between, while 9 (16.7%) experienced pain attacks without pain in between. Fourteen (25.9%) patients with DM had persistent pain with pain attacks, while 13 (24.1%) experienced persistent pain with slight fluctuations. Only 8 (14.8%) experienced radiating pain.
Clinical characteristics of DM with NP
The mean age of our patients with type 2 DM with NP was 62.4 ± 10.9 years, which was significantly higher than the mean age of the patients with DM without NP [58.9 ± 11.7 years (P = 0.05)].
There was no statistically significant difference in disease duration between DM patients with and without NP (P > 0.05, [Table 2]). Though there was a trend of increasing disease duration in the DM patients with NP, other clinical characteristics such as glycaemic status did not differ between the two groups as shown in [Table 2].
|Table 2: Clinical characteristics of DM cohort with and without neuropathic pain|
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Treatment pattern in PDN
Out of 54 type 2 DM patients 44 (81.5%) with NP were on treatment at the time of the study, while 10 (18.5%) were treatment naïve. However, out of the 44 patients on treatment, only 9 (20.5%) were on evidence-based treatment (4 on pregabalin, 1 on gabapentin, and 3 on amitriptyline), and the remaining 35 (79.5%) were on inappropriate treatment (28 on carbamazepine, 1 on acetaminophen, 3 on vitamin B, and 3 on nonsteroidal anti-inflammatory drugs) (χ2 = 82.1, P = 0.000).
| Discussion|| |
The frequency of NP in type 2 DM patients attending the LUTH was 21.6% that is higher than the worldwide prevalence estimate of 15%. 
A previous study in Jos, Nigeria, estimated the frequency of diabetic sensorimotor neuropathy to be 40.4%  A previous study by Okubadejo et al.  at this same facility estimated the prevalence of symptomatic somatic neuropathy to be 47.6%.  However, these studies did not distinguish between painful and painless DM neuropathy.
The frequency of PDN obtained in this study is also higher than what was obtained in Turkey where Erbas et al.  obtained a prevalence of 14% in their population of people with DM. Though the Turkey study also involved patients attending diabetes outpatient clinics of university hospitals, the study population consisted of both type 1 and type 2 DM patients unlike the current study. Their study instrument was the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS) scale that included both symptoms and signs as opposed to the present study that used the PDQ that focused mainly on symptoms.
Bouhassira et al.  in a multicenter study involving 1,194 type 1 and type 2 diabetics obtained a prevalence of 18% in their subcohort of type 2 DM. They evaluated diabetics already screened for peripheral neuropathy with a Neuropen for NP using the Douleur Neuropathique 4 (DN4) questionnaire.
The prevalence rate in the present study is, however, much lower than figures obtained from a university clinic in Saudi Arabia where prevalence rate of painful diabetic peripheral neuropathy was 65.3%.  Their prevalence rate is much higher than the global prevalence estimates. They used the DN4 to screen for NP but found that prevalence was higher in type 1 than type 2 diabetics. The authors postulated poor glycaemic control to be responsible for the higher than expected prevalence; however, they did not assess their populations' glycaemic status.
Our DM patients with NP were significantly older than those without NP. This is similar to findings in Turkey and Saudi Arabia and agrees with the literature. , Also NP in our DM cohort occurred more in females which is in agreement with findings from Saudi Arabia  and Turkey.  In contrast to those two studies, our study did not reveal a relationship between diabetic NP and duration of disease. DM patients with PDN historically have longer disease duration than those without PDN. Also though DM NP correlates with poor glycaemic status in the literature, this was not corroborated by our findings. There was no difference in glycaemic profile [fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c)] between DM patients with NP and those without NP. This is in keeping with earlier work done at the same center on symptomatic somatic neuropathy in type 2 DM. 
Only 20.5% (N = 9) of our type 2 DM patients experiencing NP received first line agents for treatment according to international guidelines. , The first line agents for treatment of diabetic NP are pregabalin, duloxetine, nortriptyline, gabapentin, venlafaxine, and tramadol. This low frequency could be attributed to high cost of these first line agents in our environment and nonavailability. Also the side effect profile of the tricyclic antidepressant amitriptyline could contribute to its underutilization as nortriptyline is not readily available in our environment. More than half of our patients were on carbamazepine that is not in line with international guidelines for the management of diabetic NP. , The high use of carbamazepine could be attributed to its availability, its cost (cheaper than the other first line agents such as pregabalin and gabapentin), and the fact that it has a better side effect profile than amitriptyline. Other agents used for treatment in this study that are not in compliance with international guidelines on treatment of NP in type 2 DM patients are acetaminophen, nonsteroidal anti-inflammatory drugs, and vitamin B.
In conclusion, the frequency of diabetic NP in type 2 DM patients attending our health-care facility is higher than the worldwide prevalence. Also management of these patients needs to conform to international best practice to improve symptomatology and patients' quality of life.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al
. Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology 2008;70:1630-5.
Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: Epidemiology, pain description, and quality of life. Diabetes Res Clin Pract 2000;47:123-8.
Smith AG, Singleton JR. Diabetic neuropathy. Continuum (Minneap Minn) 2012;18:60-84.
Low PA, Dotson RM. Symptom treatment of painful neuropathy. JAMA 1998;280:1863-4.
Pourmand R. Diabetic neuropathy. Neurol Clin 1997;15:569-76.
Spruce MC, Potter J, Coppini DV. The pathogenesis and management of painful diabetic neuropathy: A review. Diabet Med 2003;20:88-98.
Boulton AJ. What causes neuropathic pain? J Diabetes Comp 1992;6:63-8.
Veves A, Young MJ, Boulton AJ, Manes C. Differences in peripheral autonomic nerve function measurement in painful and painless neuropathy. A clinical study. Diabetes Care 1994;17:1200-2.
Baron R. Peripheral neuropathic pain: From mechanisms to symptoms. Clin J Pain 2000;16(Suppl):S12-20.
Haigh RC, Blake DR. Understanding pain. Clin Med 2001;1:44-8.
Scadding JW. Development of ongoing activity, mechanosensitivity, and adrenaline sensitivity in severed peripheral nerve axons. Exp Neurol 1981;73:345-64.
Ziegler D, Mayer P, Wiefels K, Gries FA. Assessment of small and large fibre function in long-term type 1 (insulin-dependent) diabetic patients with and without painful neuropathy. Pain 1988;34:1-10.
Wunderlich RP, Peters EJ, Bosma J, Armstrong DG. Pathophysiology and treatment of painful diabetic neuropathy of the lower extremity. South Med J 1998;91:894-8.
Greene DA, Lattimer SA, Sima AA. Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 1987;316:599-606.
Vinik AI, Park TS, Stansberry KB, Pittenger GL. Diabetic neuropathies. Diabetologia 2000;43:957-73.
Boulton AJ, Vinik AL, Arezzo JC, Bril V, Feldman EL, Freeman R, et al
. Diabetic neuropathies: A statement by the American Diabetes Association. Diabetes Care 2005;28:956-62.
Zochodne DW. Diabetic polyneuropathy: An update. Curr Opin Neurol 2008;21:527-33.
Calcutt NA, Dunn JS. Pain: Nociceptive and neuropathic mechanisms. Anesthesiol Clin North America 1997;15:429-44.
Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: Epidemiology, natural history, early diagnosis, and treatment options. Pain Med 2008;9:660-74.
Veves A, Manes C, Murray HJ, Young MJ, Boulton AJ. Painful neuropathy and foot ulceration in diabetic patients. Diabetes Care 1993;16:1187-9.
Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care 2003;26:1790-5.
Sadosky A, McDermott AM, Brandenburg NA, Strauss M. A review of the epidemiology of painful diabetic peripheral neuropathy, postherpetic neuralgia, and less commonly studied neuropathic pain conditions. Pain Pract 2008;8:45-56.
Ugoya SO, Echejoh GO, Ugoya TA, Agaba EI, Puepet FH, Ogunniyi A. Clinically diagnosed diabetic neuropathy: Frequency, types and severity. J Natl Med Assoc 2006;98:1763-6.
Okubadejo NU, Ohwovoriole AE. Prevalence and associated factors of symptomatic somatic neuropathy in type 2 diabetes. Niger J Med 2004;7:4-8.
Erbas T, Ertas M, Yucel A, Keskinaslan A, Senock M; TURNEP Study Group. Prevalence of peripheral neuropathy and painful peripheral neuropathy in Turkish diabetic patients. J Clin Neurophysiol 2011;28:51-5.
Bouhassira D, Van Acker K, Weiss S, Matthys K, Mathieu C, Colin I. 260 Prevalence of polyneuropathy with or without neuropathic pain in Type 1 and 2 Diabetic patients. Eur J Pain 2007;11:S115.
Halawa MR, Karawagh A, Zeidan A, Mahmoud AE, Sakr M, Hegazy A. Prevalence of painful diabetic peripheral neuropathy among patients suffering from diabetes mellitus in Saudi Arabia. Curr Med Res Opin 2010;26:337-43.
Brownlee M, Aiello LP, Cooper ME, Vinik AI, Nesto RW, Boulton AJM. Complications of diabetes mellitus. In Melmed S, Polonsky KS, Larson PR, Kronenberg HM eds. William′s Textbook of Endocrinology. Philadelphia: Saunders. p. 1462-551.
Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, et al
. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010;17:1113-e88.
Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, et al
.; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evidenced-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011;76:1758-65.
[Table 1], [Table 2]