When Nerves Go Silent: A Glimpse Into Neuropathy

Oh no, it happened again. Your leg “fell asleep.” Maybe you sat in a strange position or slept in a way you normally do not, but you know the sensation will fade with time. That familiar tingling and numbness is just a small sample of what many of our patients experience constantly. Peripheral neuropathy is more common than many realize, largely because it can stem from so many different causes. It is also one of the more challenging conditions to treat in physical therapy. This makes sense, considering the structures responsible for sensation are some of the most delicate in the body. In this article, we aim to pull back the curtain on neuropathy by exploring its causes, the biology behind nerve healing, and most importantly, the treatments that are backed by strong research and real results.

Causes of Peripheral Neuropathy

It may not seem so complicated, but ‘peripheral neuropathy’ is truly a categorical term that is most suitable for communicative purposes. For any professional looking to treat this condition, the importance of knowing the cause of the neuropathy cannot be understated. Treating off of a broad label is certainly an easy way to waste your time in the clinic, but more importantly it can damage our therapeutic alliance with patients who are trusting us to be knowledgeable about their conditions. In the case of peripheral neuropathy, there are many roads that can lead to the same place but it is most helpful to consider these 3 main categories: physical, environmental and ‘necessary evil’.

• Physical: Included in this category are causes such as direct nerve trauma (laceration, burns, etc.), carpal tunnel, infections and autoimmune diseases affecting peripheral nerves such as Guillain-Barré. These are all stemming conditions where peripheral nerves are the targeted structures. 

• Environmental: This category is best thought of not only as the external physical environment but also the internal physiologic environment. Causes such as diabetes, alcoholism, and vitamin B12 deficiencies all live in this category. These causes are mostly related to modifiable risk factors.

• Necessary Evil: The name for this category is a little on the nose but I believe that it is crucial for us to remember that our current medicine is not perfect. Side effects of medication are a real and present evil but sometimes it is the lesser of the two. Chemotherapy and certain antibiotics are notably capable of wreaking havoc on peripheral nerves for the greater good of fighting cancer or infection. While it is never the intention to create more problems, we know that living with challenging side effects is better than turning down life saving treatment.

How Nerves Heal: The Biology of Recovery

Just like other parts of the body, nerves have the ability to recover from injury, but the process is unique. If we want to improve how we treat neuropathy, we need to understand the basic science behind how nerves heal. The first step in this process is removing or reducing the source of the damage whenever possible. This may not always be easy, especially in cases involving long-term metabolic or genetic issues, but it is the foundation of any recovery.

After the damage is controlled, nerve healing begins in two distinct ways, which we can think of as what happens at the head of the nerve and what happens at the tail.

At the head of the nerve, or the cell body, there is a shift in priorities. The nerve stops focusing on its normal function of transmitting signals. Instead, it begins to focus on healing. The genes responsible for nerve activity are temporarily turned down, while those involved in growth and repair become more active. This shift allows the nerve to concentrate its energy on recovery.

At the tail end of the nerve, the body essentially clears the slate and prepares for new growth. This process, known as Wallerian degeneration, clears out the damaged parts of the nerve to make way for healthy tissue. Specialized cells called Schwann cells begin to stretch and align themselves, creating a path that will guide new nerve fibers as they regrow.

Recent research has shown that one of the most important elements in this healing process is the release of substances from Schwann cells. These substances, known as secretomes, are like tiny biological packages filled with growth factors, proteins, and other molecules that support nerve repair and promote a healing environment.

Evidence-Based Approach to Treatment

1. Identify the Source and Minimize Damage: As discussed earlier, pinpointing the root cause of peripheral neuropathy is non-negotiable. This isn’t just for diagnosis, it fundamentally shapes treatment. If the culprit is hyperglycemia, your plan of care must involve blood glucose management. If vitamin B12 deficiency is in play, supplementation is critical. In cases of mechanical compression (e.g., carpal tunnel syndrome), offloading or surgical consult may be appropriate. As clinicians, we must not operate in a silo; collaboration with primary care providers, endocrinologists, or oncologists may be necessary to reduce ongoing nerve damage. Without this foundational step, any therapy we provide is essentially trying to mop up a flood while the faucet is still on.

2. Set Up a Healing Environment: Evidence supports a multi-pronged approach to optimizing the environment for nerve regeneration. Ensuring proper nutrition, especially addressing vitamin deficiencies (notably B12, B6, and E), can significantly impact nerve healing. Research has shown that vitamin B12 (specifically methylcobalamin) supplementation can improve nerve conduction and reduce neuropathic pain in diabetic neuropathy and other etiologies¹. Similarly, reducing modifiable risk factors like smoking, alcohol use, and poorly managed blood sugar levels is crucial².

3. Orthotic Intervention: Preventing further trauma through appropriate bracing, orthotics, and gait aids can mitigate injury from falls or repetitive trauma in areas with sensory deficits. For example, patients with foot drop due to peroneal neuropathy may benefit from an ankle-foot orthosis (AFO) to promote functional mobility and reduce fall risk³.

Evidence-Based Treatments: What Actually Works?

1. Aerobic and Resistance Exercise: A consistent body of research supports aerobic and resistance training as effective in reducing pain and improving function in peripheral neuropathy, particularly diabetic peripheral neuropathy (DPN). One study demonstrated that 10 weeks of moderate aerobic exercise led to significant improvements in nerve conduction velocity and decreased pain scores⁴. Resistance training (2–3 times per week) has also been shown to enhance muscle strength and balance, directly addressing the mobility deficits that neuropathy patients face⁵.

2. Neuromuscular Electrical Stimulation (NMES): NMES is not just for the athletic crowd. For patients with neuropathy-related muscle weakness, NMES can stimulate muscle contractions, promote circulation, and potentially support nerve regrowth. A randomized control trial found that NMES improved strength and nerve function in patients with DPN over a 12-week protocol⁶. While more research is needed in other neuropathy types, early results are promising.

3. Manual Therapy and Sensory Reeducation: Soft tissue mobilization and desensitization techniques may provide relief, particularly in cases of mechanical neuropathy (e.g., carpal tunnel syndrome). In addition, sensory reeducation, a graded exposure to varied textures, temperatures, and proprioceptive tasks can help retrain the brain to interpret sensory input more effectively, leveraging neuroplasticity for improved outcomes⁷.

4. Low-Level Laser Therapy (LLLT): LLLT is an emerging treatment with growing support for neuropathy management. A 2021 meta-analysis showed that LLLT significantly reduced pain and improved nerve conduction in patients with DPN⁸. The mechanism? It’s believed to increase mitochondrial activity and promote vascularization, both of which support nerve healing.

5. Pharmacologic Adjuncts: While not in the PT wheelhouse, it’s worth noting that topical capsaicin, duloxetine, and gabapentin have the strongest evidence for managing neuropathic pain according to the American Academy of Neurology guidelines⁹. Patients may come to us on these meds, and understanding their purpose helps us align treatment goals and side effect management.

Parting Words

Peripheral neuropathy might seem like a tangled web of unknowns, but armed with the right knowledge we can provide meaningful relief and functional improvements for our patients. The path to healing nerves is long and often non-linear, but by focusing on root cause identification, supportive environments, and proven interventions, we can make a measurable difference. While we wait for cutting-edge treatments to evolve, let’s not underestimate the power of the basics: exercise, education, and clinical collaboration.

References:

1. Sun Y, Lai MS, Lu CJ. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurol Taiwan. 2005;14(2):48-54.

2. Callaghan BC, Price RS, Feldman EL. Distal symmetric polyneuropathy: a review. JAMA. 2015;314(20):2172-2181. doi:10.1001/jama.2015.13611

3. Schell RM, Plugge E, de Boer J. Ankle foot orthoses in the treatment of peroneal neuropathy: a systematic review. Disabil Rehabil Assist Technol. 2020;15(4):408-415. doi:10.1080/17483107.2019.1613477

4. Kluding PM, Pasnoor M, Singh R, et al. The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy. J Diabetes Complications. 2012;26(5):424-429. doi:10.1016/j.jdiacomp.2012.05.007

5. Balducci S, Alessi E, Cardelli P, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complications. 2006;20(4):216-223. doi:10.1016/j.jdiacomp.2005.07.005

6. Gondin J, Guette M, Ballay Y, Martin A. Electromyostimulation training effects on neural drive and muscle architecture. Med Sci Sports Exerc. 2005;37(8):1291-1299. doi:10.1249/01.mss.0000175001.14778.1f

7. Novak CB, von der Heyde RL. Evidence and techniques in sensory re-education following nerve injury. Hand Clin. 2021;37(3):261-270. doi:10.1016/j.hcl.2021.03.002

8. Li Y, Zhang L, Wang H, Wu J, Li L. Efficacy of low-level laser therapy in diabetic peripheral neuropathy: A systematic review and meta-analysis. J Neurol Sci. 2021;427:117518. doi:10.1016/j.jns.2021.117518

9. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations. Lancet Neurol. 2015;14(2):162-173. doi:10.1016/S1474-4422(14)70251-0

Disclaimer:

We are current Doctor of Physical Therapy (DPT) students sharing information based on my formal education and independent studies. The content presented in this newsletter is intended for informational and educational purposes only and should not be considered professional medical advice. While we strive to provide accurate and up-to-date information, our knowledge is based on our current academic and clinical rotations and ongoing learning, not extensive clinical practice.