Tired of Hurting: The Frustrating Road to Treating Diabetic Neuropathy.

I. Introduction

"For millions living with diabetes, the burning, tingling pain of peripheral neuropathy isn't just a symptom — it's a daily battle with nerves gone rogue."  It's a relentlessly painful condition for many diabetic people that cuts into every facet of the sufferer's life.  It is associated with depression, loss of productivity, and impaired quality of life.

Current estimates suggest that there are 425 million people with diabetes worldwide, and up to 1/3 to 1/2 of these patients will develop painful (DPN).  The condition of DPN comprises up to 27% of the overall cost of treating diabetes. 

DPN is not a disease itself but rather a condition occurring as a result of having high blood sugar. There is no cure for this condition; management is the only option once you have it.   If you are one of those few million people with painful DPN, life can sometimes be a frustrating experience in trying to find relief from symptoms.    People who suffer from this condition are reminded of it every single day, no matter how effective the treatments may be.  This article will discuss the changes to the peripheral nerves that occur with diabetic peripheral neuropathy (DPN), current treatment options, patient frustrations experienced by those living with this condition, and new treatments on the horizon.

II. What's Happening in the Nerves with High Blood Sugar

Damage to peripheral nerves from high blood sugar occurs as a result of several mechanisms that damage the tiny blood vessels that feed your nerves.   The blood supply to those nerves has only a few tiny arteries called arterioles that penetrate the endoneurium or covering of the nerve.  Damage occurs over time as excess sugar in the blood alters how the nerves use energy, causing harmful substances to accumulate inside them. Damage also leads to the production of toxic molecules that create stress and inflammation in the nerves, as well as reduce the ability of nerve cells to receive oxygen and nutrients. All of this combined can slow down nerve function and even cause nerve damage, which is what leads to diabetic nerve damage, especially in the hands and feet, with symptoms typically starting in the feet and progressing up the legs in a pattern known in the medical community as a stocking-glove pattern.  As the disease progresses, the affected person will eventually start experiencing symptoms in the hands. 

III. What Doctors Use to Treat DPN

1.  Control the blood sugar.  

All medical providers begin treatment for DPN by focusing on controlling blood sugar levels. To understand the importance of this, imagine a firefighter trying to put out a fire while the gas leak that started it is still fueling the flames. If the fuel keeps flowing, the fire—and in this case, the nerve damage—only gets worse.

 We can also use this same metaphor to explain why it's not curable.   The fire might be out, but the damage that is left is final.  Yet, strict blood sugar control can halt or help slow the progression of the condition. 

2.   Treatment combinations are used simultaneously to provide the best results.  

A lifelong commitment to lifestyle changes, used in conjunction with any treatment method, will improve tolerability and long-term outcomes. Good sleep hygiene measures to enhance the quality of sleep is essential. The pain of DPN tends to bother people more at night than in the day.   Regular daily exercise helps control blood sugar and regulate mood. Daily foot checks for wounds or sores can help prevent serious skin conditions and infections. Regular monitoring by your medical provider is also integral to maintaining adequate DPN treatment. 

3. Oral medication therapy is a standard treatment option. 

The FDA has currently approved only three medications for the treatment of DPN. However, many medical providers widely accept and use other off-label medications as helpful options.  It is also important to note that there is usually no single drug that controls symptoms well, and many people end up taking more than one drug to try and control their symptoms.  Additionally, some research studies have found taking high doses of a single medication or taking multiple medications is no better one way or another.   

Pregabalin, approved by the FDA in 2004, is a medication in the class of antiseizure or gabapentinoids. It is one of several first-line treatment options, meaning it is the approach doctors should try first. Of others in this class, gabapentin is probably the most commonly tried, but carbamazepine, topiramate, or valproic acid might also be considered.    

Medical providers also use antidepressants in the treatment of painful DPN.  The FDA approved duloxetine in 2004 for use in the treatment of DPN.  Venlafaxine, in the same drug class and similar to duloxetine, has also been used. Several drugs from the tricyclic antidepressant drug class, such as amitriptyline, nortriptyline, and desipramine, are also used.  In addition to their effect on nerve pain, they can provide the added benefit of control of symptoms of depression.

The medication Tapentadol is a newer opiate that is FDA-approved for the management of painful DPN. However, medical professionals consider this medication to be third-line therapy for use after several others have been tried and failed. It is different than traditional opiates like morphine or oxycodone, which are generally not recommended as their low therapeutic benefit typically do not outweigh the concern for tolerance, misuse, or abuse with long-term opiate medication.   There is some positive evidence for tramadol or methadone for its NMDA receptor activity, which is known to have a more positive effect on nerve pain.

 4.  Topical pain medication

Capsaicin is a topical treatment derived from chili peppers that desensitizes the nerves in the skin over time.  There is an over-the-counter preparation that helps some people.   It needs to be Applied 3-4 times a day over a period of two months to see any results. 

Capsaicin in high concentration, by the brand name Qutenza, was approved by the FDA for the treatment of DPN. However, the delivery method is a patch form that a healthcare provider must apply, as it requires a topical anesthetic to reduce pain upon application. Patients also need to be monitored closely for an hour after treatment for potential side effects or complications. 

Many people find over-the-counter lidocaine patches helpful, though results are temporary, and you can only apply for 12 hours at a time before needing to be removed. 

Prescription-based topical pain creams that contain a combination of agents, such as lidocaine, gabapentin, amitriptyline, clonidine, and ketamine, are often recommended for symptom management. Clinical data supporting these medications is limited and inconsistent. However, they are typically tolerated well with fewer side effects and low toxicity. The downside is that people must apply the topical medication several times a day to maintain the effect, and you can only obtain it from a specialized compounding pharmacy.

5. Non-Medication, Alternative Treatments.  

Some literature discusses the effectiveness of acupuncture, electromagnetic stimulation, neural electrical stimulation, and Laser therapy. These services are more likely to be offered in natural or holistic type clinics.  

6. Other Non-medication, Neuromodulation Treatments.  

These are devices that can affect the brain's interpretation of pain. Think of neuromodulation as a "volume control" for the nervous system. It's a way to change (or "modulate") how nerves behave. Transcutaneous Electrical Nerve Stimulation (TENS) therapy is widely recognized and is readily available over the counter, making it relatively inexpensive.

Scrambler therapy and Frequency Rhythmic Electrical Modulation System (FREMS) therapy target different nerve fibers than a TENS unit. Healthcare providers typically apply these neuromodulating devices topically in clinical settings, and they work through mechanisms distinct both from each other and different from those of TENS.

The spinal cord stimulator, a minimally invasive implantable device, typically has been reserved for low back pain, radicular symptoms, and failed back syndromes. The high-frequency 10 kHz spinal cord stimulator has received FDA approval for the treatment of PDN in 2023.

There is also an implantable drug delivery device that can deliver a limited number of medications directly into the spine to modulate pain. There is one specific medication derived from snail venom for nerve pain called Prialt. Doctors typically reserve this method to treat severe chronic nerve pain when all other treatments have been tried and have failed—as a last resort.  

6.   Mental health support like CBT (cognitive behavioral therapy) for coping with chronic pain.

Psychological services such as Cognitive Behavioral Therapy (CBT)  can be an integral part of pain management by changing thoughts, feelings, and behaviors about how you interpret your pain experience. This type of therapy helps you learn to deal with this condition on a day-to-day basis. 

IV. You Need a Team, Not Just One Doctor

Managing DPN often requires assistance from multiple specialists, including a primary care provider, a diabetes specialist, a pain specialist, a neurologist, a physical therapist, and a mental health provider, among others, depending on your case. Talk to your doctor or someone you trust if you feel stuck or unheard. This same advice also applies to caregivers who need to prioritize their health.

III. Why Treating DPN Is So Frustrating.

1.  Barriers to treatment.  

Today's healthcare is challenged by a declining workforce, which limits people's access to specialists and is not expected to improve in the future. Appointments with specialists like neurologists or pain doctors can take weeks or months, especially if there are none of these types of specialists near you.  Some smaller towns or rural areas may not have these specialists within hundreds of miles, making it nearly impossible for some people to access this type of care.

Cost and insurance issues are also a concern for many, as healthcare costs continue to rise year after year. Additionally, many of these medications and treatments have significant co-pays, making them cost-prohibitive, or they're not covered at all.  

2. Side effects.  

Significant side effects, such as drowsiness and abnormal thinking, as well as others, are well known from the most commonly prescribed medications.  

3.  Expected pain relief is modest and slow.

Medical treatments for DPN are largely not extremely successful, with a goal of a 30% reduction in pain being considered statistically meaningful to the medical community.   Additionally, everyone responds differently, and what works for one person might not help another at all.  Research studies have been unable to clearly identify a specific medication protocol that works well for everyone,  making choices by medical providers often a system of old-fashioned “trial and error".  Medical providers usually prescribe medications in titrating amounts over a 4 to 6-week trial. Pain relief is a slow process that can take months and become frustrating for the patient who can’t sleep at night or have difficulty walking during the day. 

IV.  What’s on the Horizon-Emerging Therapies and Medications? 

New avenues for research and the development of novel therapeutic targets aimed at modulating central pain pathways in DPN are underway, with new treatments focusing on nerve regeneration.  This includes but is not limited to gene therapy and stem cell therapy. There are also new developments in how medication is delivered, such as nano-technology to enhance action to specific target areas.

Other newer and upcoming treatments are focused on restoring normal nerve function.  New drugs currently used for diabetes treatment, such as Jardiance and Farxiga, have been shown to reduce some of the stress and inflammation on nerve fibers.  Other medications, such as Ozempic and Wygovy, have been shown to have anti-inflammatory and direct neuroprotective properties.

Metanx is a neutraceutical medical food containing a mixture of vitamins that reduce inflammation and stress of vascular endothelium. The antioxidant alpha-lipoic acid has been shown in research to have many positive effects on nerve cells.

Some research has shown probiotic supplementation helps reduce inflammation in the gut, which can affect nerve health. Microbiota therapy, which involves the transfer of fecal material from healthy donors to patients with DPN, aims to restore gut microbial balance and reduce inflammatory markers.

V. Wrapping It All Up 

Painful DPN is a tough condition to live with, both physically and emotionally.  You can't easily fix or cure it, but catching it early gives you the best chance to lessen its severity and slow its progression over time.

A multidisciplinary approach is typically required to manage DPN symptoms, and regular appointments with your healthcare provider are a crucial step in diagnosis and management.  Treatment options are numerous but often limited when used as a single agent. Most patients suffering from DPN will require more than one treatment modality to achieve satisfactory results.    

However, there is hope on the horizon, with emerging therapies offering improved benefits, including nerve regeneration and restoration of normal function, some of which are already in use today.  

If you are struggling or not happy with the results you are receiving, do some research on your own. Learn about some of these alternate treatments. Speak with your healthcare professional or a trusted individual to help you in this process. You don't have to do it alone. Additionally, there are support groups that can help you manage and get through the day-to-day challenges of living with painful DPN.  One last word of caution: Be wary of anyone promoting a supplement, medication, or treatment as a miracle cure—it will likely leave you disappointed and with less money.

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