Current Strategies for the Management of Painful Diabetic Neuropathy

Abstract

The development of painful diabetic neuropathy (PDN) is a common complication of chronic diabetes that can be associated with significant disability and healthcare costs. Prompt symptom identification and aggressive glycemic control is essential in controlling the development of neuropathic complications; however, adequate pain relief remains challenging and there are considerable unmet needs in this patient population. Although guidelines have been established regarding the pharmacological management of PDN, pain control is inadequate or refractory in a high proportion of patients. Pharmacotherapy with anticonvulsants (pregabalin, gabapentin) and antidepressants (duloxetine) are common first-line agents. The use of oral opioids is associated with considerable morbidity and mortality and can also lead to opioid-induced hyperalgesia. Their use is therefore discouraged. There is an emerging role for neuromodulation treatment modalities including intrathecal drug delivery, spinal cord stimulation, and dorsal root ganglion stimulation. Furthermore, consideration of holistic alternative therapies such as yoga and acupuncture may augment a multidisciplinary treatment approach. This aim of this review is to focus on the current management strategies for the treatment of PDN, with a discussion of treatment rationale and practical considerations for their implementation.

Treatment of Painful Diabetic Neuropathy—A Narrative Review of Pharmacological and Interventional Approaches

“…The first treatment for pain, including chronic pain, is often pharmacotherapy, but neuropathic pain is not the same as musculoskeletal pain, and commonly used analgesics such as opioids are not appropriate or effective for managing chronic neuropathic pain such as PDN [15,16]. The pharmacotherapies approved and used to manage PDN are mostly not traditional analgesics or opioids that can be taken "as needed" but rather agents such as anticonvulsants or antidepressants that must be taken regularly for a period of time to achieve full effect [17]. There are now more pharmacotherapies available for treating PDN than in the recent past, which are summarized in Table 2, and clinicians should consider patient-specific factors such as age, quality-of-life goals, functional status, and comorbidities when determining appropriate management [3,[18][19][20].…”

“…In addition to duloxetine, the SNRI venlafaxine and TCAs have shown evidence of efficacy for PDN and may be considered for PDN according to recommendations by the ADA, although they have not received FDA approval for this use [18]. Venlafaxine is mechanistically similar to duloxetine, but there are fewer published data for this drug in PDN [17]. An extended release (ER) formulation of venlafaxine was tested in a 6-week, double-blind, RCT in 244 subjects with PDN, and the investigators found that doses from 150 mg to 225 mg/day resulted in 50% lower pain scores than the baseline, which was significantly greater than the 27% pain reduction in the placebo group [41].…”

“…The reported AEs in this trial were nausea, somnolence, and electrocardiogram abnormalities, and there was no significant difference in the rate of serious AEs between subjects receiving placebo (10%) or 150-225 mg/day venlafaxine ER (12%). Amitriptyline is the most commonly used TCA for treating PDN, but the high risk of AEs requires careful monitoring and this drug is best suited as a last resort [17]. A metaanalysis of trials testing amitriptyline in subjects with PDN included four studies with doses ranging from 10 mg to 90 mg/day for 12 to 14 weeks [34].…”

“…The authors concluded amitriptyline was 1.95-fold more effective than placebo at producing at least 50% pain relief, which was not significant, but the odds ratio (OR) for subject withdrawals due to AEs for amitriptyline was 10.24 relative to placebo and 7.03 relative to gabapentin [34]. Common AEs encountered with TCAs include gastrointestinal issues, orthostatic hypotension, dry mouth, urinary retention, and QTc prolongation, and this safety profile reflects concurrent actions at histaminergic, adrenergic, and cholinergic receptors [17].…”

Therapeutic role of yoga in neuropsychological disorders

“…Yoga and neuropathy: Peripheral neuropathy is a common neurological condition due to physical nerve injury, diabetes mellitus, autoimmune disorders, malignancy, kidney failure, nutritional deficiencies, systemic disorders, and idiopathic neuropathies, which can implicate the motor, sensory, and/or autonomous peripheral nerves[ 102 , 103 ]. Several lines of evidence suggest that yoga may alleviate symptoms of various neuropathies[ 104 , 105 ].…”