Sensory profile and its impact on quality of life in patients with painful diabetic polyneuropathy

Introduction

Neuropathy is one of the most common complications in both type I and type II diabetes mellitus. It can present in various forms, as both focal or symmetric types. The most common form is a chronic, symmetrical, length-dependent axonal sensorimotor polyneuropathy. Some patients are asymptomatic, but many patients have sensory symptoms, either negative or positive ones. These symptoms may fluctuate over time. Some of them also have pain associated with neuropathy, also known as painful diabetic neuropathy (PDN), which is strongly associated with other diabetic complications.

On the other hand, painful diabetic neuropathy is the most common cause of neuropathic pain.[1] The diagnosis of PDN is a clinical one, which relies on the patient's description of pain.[2] The symptoms are distal, symmetrical, often associated with nocturnal exacerbations, and commonly described as prickling, deep aching, sharp pain, like an electric shock, and burning with hyperalgesia and frequently allodynia upon examination.[2]

These symptoms were always categorized using rating scales and standard pain questionnaires to assess the frequency and severity of painful symptoms, and treatment responses. Moreover, each type of pain is believed to be caused by different pathophysiological mechanisms, therefore, each neuropathic pain medication might have a different effect on sensory symptoms.[2]

Having PDN also has a significant negative effect on quality of life, especially in physical terms, and a significantly worse trajectory of quality of life outcomes over time and long-term increased total costs.[34]

Results

Thirty three patients were included in this study. Their details were broken down by gender and are summarized below in Table 1. There was no significant difference in demographic information, except height.

Table 1 Baseline patient characteristics

Regarding pain characteristics, NPS, SF-MPQ and SF-36 data were reported in Tables 2–4. From NPS, the most common type of pain was sharp pain and the least common one was itching. The unpleasantness score was 6.9. This was high. The SF-MPQ score showed an average score across all components. The average VAS was 53 mm. Out of the ten types of pain listed in the NPS questionnaires, 14 of 33 (42.2%) had four types of pain or more, 11 of 33 (33.3%) had three types, 7 of 33 (21.1%) had two types and only one out of 33 (3.03%) of patients had one type. Multiple comparisons and association analysis between pain intensity, pain type and baseline characteristics revealed that high pain intensity and presence of any types of pain were significantly associated with the female subjects (P = 0.03) and in subjects with creatinine level less than 1.2 mg/dl (P < 0.01).

Table 2 Neuropathic pain scale

Table 3 Short-form McGill pain questionnaire

Table 4 Comparison of SF-36 mean score in relevant studies

Regarding SF-36, the physical function was most affected and the social function was least affected. The SF-36 data from each disease and healthy subjects were compared in Table 4.

Discussion

DPN is still a clinical diagnosis, despite the advance in neurophysiologic studies. Incorporating standard pain questionnaires in clinical evaluation will aid in early diagnosis and better management in these patients.[9] In this study, we used a DN4 questionnaire, which has been validated as a reliable screening tool for neuropathic pain in diabetic patients with the cut-off point score of 4.[10] The questionnaires can be used to screen and differentiate between neuropathic and non-neuropathic pain.[11]

The sensory profile in our DPN patients showed that sharp pain is the most common and the least common is itching. This NPS and SF-MPQ data is in line with previous reports.[1213] Almost all patients had more than one type of pain which adds more complexity to any clinical evaluation. This may imply that the mechanism of pain is most likely from small nerve fibers, rather than from large fiber dysfunction. Previous clinical and electrophysiological studies also confirmed that neuropathic pain in diabetic polyneuropathy is not associated with the degree of involvement of large diameter sensory fiber or diabetes severity.[14]

Interestingly, when looking at the sharp pain, the duration of diabetes was not associated with painful symptoms. This is due to the history of small fiber neuropathy which can occur in pre-diabetes stage.[15] Although the pain of PDN may resolve completely over time in some patients, in those in whom painful neuropathic symptoms had persisted over five years, no significant improvement in pain intensity was observed.[16] In our patients, the mean duration of pain was four years. This indicated the persistency of pain and it was probably less likely to resolve spontaneously. Female subjects were predictive of pain,[9] as in this present study. However, creatinine levels lower than 1.2 mg/dl was also associated with a higher risk of PDN, which has never been reported before and needed to be confirmed in the future with larger dataset.

The presence of DPN significantly affected patients’ quality of life, especially physical function. Moreover, it was associated with significantly worse trajectory of quality of life outcomes over time and long-term increased total costs, when compared to patients with non-painful diabetic polyneuropathy. The presence and severity of neuropathic pain were associated with greater impairments in a number of important health-related quality of life (HRQoL) domains.[31718] This data was in line with previous reports in diabetic patients whether they had PDN or not.[192021] When comparing with the normal healthy Thai population with regards to the SF-36 subcategories[8] in Table 4, DPN had a detrimental effect in all subcategories, except vitality. Moreover, PDN patients had poorer physical function than other chronic neurological illnesses or than the general diabetic population [Table 4].[22] Their quality of life (QOL) was similar to diabetic foot ulcer patients which indicated severe disability.[20]

A recent American Academy of Neurology evidence-based review has used VAS as a primary measure and physical function and QOL, e.g., using SF-36 as guidelines for an efficient assessment to formulate the recommendation for pharmacological treatment of painful diabetic polyneuropathy (PDN).[23] However, in a clinical trial situation, quantitative sensory testing (QST) is still necessary for a more objective measurement of outcomes, as well as HRQoL.[2425]

There were some strengths and limitations of this study which should be mentioned. This study was based on an outpatient clinic population which reflected a real-life practice. However, it was a single center study with a small number of patients. A quantitative sensory test was not performed to confirm the neuropathy. However, it might not have been necessary in this real life practice survey.

Despite the improvement in treatment modalities for chronic pain in recent years, patients with PDN continue to be inadequately treated. The different profiles of pain quality and spatial characteristics suggest that the assessment of patterns of pain symptoms might contribute to the identification of distinct pathophysiological mechanisms, subgroups of patients and the development of mechanism-based treatment approaches.[26] This will eventually improve the outcome and quality of life in these patients.