Novel and Emerging Therapies
Stem cells have emerged as an intriguing treatment for diabetic neuropathy on multiple fronts. One possible use for stem cells is treating the elevated glucose levels that cause diabetic neuropathy. Research suggests that stem cell transplantation can protect and restore the insulin-secreting cells of the pancreas, lowering blood glucose levels and relieving diabetic neuropathy and other complications (Sino Stem Cells 2013; GSCN 2013). Stem cells may also improve blood flow to damaged nerves, helping reduce pain and heal neurons crippled by diabetic neuropathy (Kim 2012). In addition, researchers found that certain stem cells, termed mesenchymal stem cells, may be able to reduce inflammation and thus relieve diabetic neuropathy pain (Waterman 2012). Stem cells continue to be developed and may become more widely available in the not-too-distant future.
Nabilone (Cesamet®) is a synthetic cannabinoid, which means it has some of the same properties as constituents of marijuana. It is sometimes used to treat nausea due to chemotherapy but may also be effective in treating pain caused by diabetic neuropathy (Toth 2012). Two different studies found that nabilone is effective at relieving diabetic neuropathic pain and also improved the mood and overall quality of life for diabetics. These studies also found that treatment with nabilone improved sleep in patients suffering from diabetic neuropathy (Toth 2012; Bestard 2011). This is important because for many, the pain of diabetic neuropathy is worse at night (Ziegler 2009). Physicians may prescribe nabilone as an off-label treatment option for painful neuropathy.
Botulinum toxin, a neurotoxin secreted by the bacterium Clostridium botulinum, blocks signaling from the neurotransmitter acetylcholine. Botulinum toxin can be injected in small quantities to temporarily disable nerves and muscles; it is often used for cosmetic reasons or to treat muscle spasticity (Jabbari 2011; Bach-Rojecky 2010). Early studies suggest that injection of botulinum toxin to sites of painful diabetic neuropathy may significantly reduce pain and improve sleep quality, though more studies are needed to determine the effectiveness of this treatment (Yuan 2009; Francisco 2012).
Transcutaneous Electrical Nerve Stimulation
Transcutaneous electrical nerve stimulation (TENS), which is used for the treatment of acute and chronic pain, utilizes small devices that deliver a small electric current through electrodes placed near the painful area (Stein 2013; Vance 2014; Coutaux 2017). One mechanisms of action involves the stimulation of networks of neurons resulting in decreased pain sensation (Vance 2014). TENS was accepted in France for reimbursement by the health insurance system in 2000 (Coutaux 2017).
Many studies have examined TENS for various types of pain, including acute pain, low back pain, osteoarthritis, labor, cancer pain, and postoperative pain (Vance 2014). In a randomized study of 31 peripheral diabetic neuropathy patients that received TENS or sham treatment for 4 weeks, 30 minutes per day, 83% of the TENS group experienced symptomatic improvement compared with 38% in the sham-treated group, pain scores in the TENS group decreased from 3.17 to 1.44, and symptoms reappeared about one month after TENS was terminated (Kumar 1997). In a randomized, single-blind, placebo-controlled study, TENS was examined in combination with amitriptyline for the management of chronic painful peripheral neuropathy in 26 patients with type 2 diabetes. All participants were prescribed amitriptyline, but after four weeks, those who failed to respond or who only partially responded were randomized to the TENS or sham group. Symptomatic improvement was reported in 85% of participants and 36% became asymptomatic. The study revealed that the effect of combining TENS and amitriptyline appears to be superior to TENS alone (Kumar 1998). In a randomized, double-blind, controlled study that enrolled 19 patients with mild-to-moderate diabetic neuropathy, TENS led to significant improvements in total symptom score after 6 weeks (-42%) and 12 weeks (-32%) of treatment (Forst 2004). In another study of 34 peripheral diabetic neuropathy patients treated with TENS, 76% of participants reported a subjective improvement in their neuropathic pain (Julka 1998). A meta-analysis of three randomized controlled trials that enrolled 78 patients showed that after four and six weeks of follow-up, mean pain score was significantly reduced, and at 12 weeks participants reported a subjective improvement in their neuropathic symptoms. No adverse effects were noted (Jin 2010). In another systematic review and meta-analysis of 12 studies, it was shown that TENS improved pain relief in participants with diabetic neuropathy, and the improvement was significantly better than in the placebo group. In addition, electromagnetic stimulation did not show an effect on pain relief (Stein 2013).
The Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology recommended, based on four studies, that TENS is “probably effective” and should be considered in the treatment of painful diabetic neuropathy. It also pointed out that more research is needed into the mechanisms of action, and more rigorous studies are required for examining the efficacy of this approach (Dubinsky 2010). Contraindications and limitations to the use of TENS include: the presence of a pacemaker if TENS is applied to the chest; loss of sensation in the area of the damaged nerve; uncontrolled seizures; certain types of damage to the spinal cord; pregnancy (except when used to treat low back pain during labor); and avoidance in the region over major neck arteries (Coutaux 2017).