Peripheral neuropathy is a painful condition that affects the peripheral nerves of the body.

These nerves are responsible for both motor and sensory functions. They receive signals from the central nervous system—for example, the brain and spinal cord—to contract the muscles, as well as send information back to the brain about the environment, like one’s temperature, position in space, and sensations felt.

In peripheral neuropathy (also called peripheral neuritis), these nerves are damaged, leading to classic symptoms of tingling, numbness, muscle weakness, and severe pain.

Over the past few decades, the incidence and prevalence of chronic illnesses such as peripheral neuropathy have skyrocketed. These conditions severely impact a person’s quality of life and can have a lasting impact on one’s physical and mental state. (1)

In this comprehensive guide, we will discuss everything you need to know about peripheral neuropathy, including the primary signs and symptoms, causes, types, diagnosis, and available treatment options.

By the end of this article, readers will be equipped with the knowledge to identify, prevent, and treat peripheral neuropathy.

Peripheral neuropathy is a relatively common medical condition that affects nerves of all types (e.g., sensory, motor, autonomic).

As the name implies, this condition is exclusive to the nerves located in the periphery since damage to the brain or spinal cord gets termed differently. (3)

By periphery, we are referring to all the nerve cell bodies outside of the central nervous system (brain, spinal cord).

Peripheral neuropathy results from direct or indirect damage to the nerve endings, which precipitates a rich clinical presentation composed of tingling, unusual sensations, numbness, weakness, lost sensitivity to fluctuating temperatures, and burning pain. (4)

Most patients who complain of peripheral neuropathy state that their symptoms are symmetrical, meaning they affect both limbs (e.g., hands, feet). For this reason, doctors often refer to the distribution of peripheral neuropathy as a ‘glove and stocking’ pattern. (5)

While authors classify this condition based on the type of affected nerves, some choose to categorize it depending on the size and extension of the damage.

The clinical presentation of peripheral neuropathy varies depending on the affected nerve and the degree of damage.

In general, a patient with peripheral neuropathy may complain of one or more of the following signs and symptoms: (6)

• Tingling in the extremities
• Extreme, sharp pain
• Loss of sensations in the hands or feet
• Loss of temperature sensation
• Weakened muscles of the arms and legs
• Dropping objects unconsciously
• Buzzing-like sensations in the arms and feet

One classic example of neuropathy that involves one nerve is carpal tunnel syndrome, where the median nerve gets trapped and damaged inside the carpal tunnel of the wrist. (7)

Depending on the affected nerve, scientists identified more than 100 types of peripheral neuropathy that present with different signs and symptoms and have their own prognoses. (8)

For simplicity’s sake, most doctors classify peripheral neuropathy into one of these categories:

Motor neuropathy

The damage in this type of neuropathies affects the nerves that control the muscles of the body, including those you use to move your hands or feet. (9)

These nerves directly connect to your muscles, forming what’s known as the neuromuscular junction (NMJ), which transmits electrical signals from the cerebral cortex to the muscle fibers under your control (for instance, when you decide to move your finger). (10)

Peripheral neuropathy of the motor nerves causes weakness, generalized fatigue, and the frequent dropping of objects. (11)

Sensory Neuropathy

In the skin, there are several neurons (i.e., nerve cells) responsible for different sensory functions, including pain receptors, temperature receptors, light-touch receptors, and proprioception (i.e., position in space). (12)

For instance, if you touch any object right now, the nerve endings will send signals to the brain, specifying its size, temperature, and texture, which allows you to sense that object.

After collecting input from the external environment, these neurons are grouped together in one big nerve that travels to the central nervous system (spinal cord → the brain).

Damage to sensory nerves results in loss of pain and temperature sensations, numbness, and tingling. (13)

Autonomic Nerve Neuropathy

While most people are aware of motor and sensory nerve functions, autonomic nerves are rarely discussed.

To understand why peripheral neuropathy causes certain signs and symptoms, we need to address the function of the autonomic nervous system.

An Overview of the Autonomic Nervous System

This system possesses a large number of nerves that can be classified into two categories:

• Nerves that belong to the sympathetic nervous system*
• Nerves that belong to the parasympathetic nervous system*

The function of the autonomic nervous system is to regulate internal processes without the need for conscious control. (14)

For instance, this system regulates heart rate, blood pressure, sweating, respiratory frequency, digestion, bowel movement inside the gastrointestinal tract, penile erection, ejaculation, and bladder emptying.

As you can guess, any damage to the nerves responsible for autonomic control results in debilitating consequences (15), such as:

• Urinary and bowel incontinence
• Disrupted peristalsis (e.g., constipation, diarrhea)
• Abnormal heart rate
• Sexual problems in men
• Cardiac palpitations*
• Hyperactive perspiration (i.e., excessive sweating) response

Combined Neuropathy

In this type of neuropathy, patients may experience a combination of the 2 or 3 types mentioned above at the same time.

The causes of peripheral neuropathy are diverse and include chronic diseases, infectious processes, and hereditary maladies.

As a baseline, you should keep in mind that individuals with a family history of peripheral neuropathy are more likely to develop this disorder even without a clear cause. (16)

With that being said, here is a list of the most common causes of peripheral neuropathy:

Diabetes mellitus

A classic example of a disease that causes peripheral neuropathy is diabetes, especially in patients who do not keep their blood sugar in check. (17)

The chances are higher if the following risk factors are present: (18)

• Advanced age (over 40 years old)
• Being overweight or obese
• Having other concurrent medical conditions (e.g., chronic blood hypertension)

Note that these risk factors could be independent triggers of peripheral neuropathy in the absence of diabetes.

Health officials from the University of Chicago’s Center for Peripheral Neuropathy (UCCPN) state that approximately 60% of diabetic patients have some degree of nerve damage that results from the high concentrations of advanced glycation end products (AGEs).

AGEs: proteins and lipids that get glycated due to the abnormally high levels of glucose in the blood. (19)

Another mechanism that explains how diabetes causes peripheral neuropathy is the interruption of blood flow to the nerves. You see, diabetes is notoriously known for damaging blood vessels, and since nerves also have a blood supply (tiny blood vessels that provide oxygen and nutrients), this could lead to impaired electrical signaling of the nerves and potentially cellular death.

Kidney damage

End-stage renal disease impairs the function of the kidneys and their ability to detoxify the body from harmful substances and chemicals.

In other words, the kidneys are responsible for cleaning the body from toxins by excreting them through the urine.

Over time, these toxins buildup, which eventually leads to neurotoxicity of the peripheral nerves. (20)

Hypothyroidism*

Hypothyroidism is a common condition that disrupts the vast majority of physiological functions, including fluid and salt regulation. (21)

As a result, the fluid accumulates in the interstitial compartment, which applies severe pressure to the surrounding nerves, causing irreversible damage. (22)

Nutritional deficiencies

The nerves need a steady supply of vitamins and minerals that ensure their structural integrity and functions. Any deficiency in these elements could lead to peripheral neuropathy. (23)

Examples include:

• Vitamin E
• Vitamin B1
• Vitamin B6
• Vitamin B12

Alcohol intoxication

Alcohol is extremely toxic to nerve tissues when consumed in large amounts and over a long time period. For this reason, the vast majority of alcoholics have some sort of nerve damage that disrupts specific motor-sensory functions. (24)

Chronic exposure to other toxins, such as glue, solvents, insecticides, lead, and mercury can also lead to peripheral neuropathy. (25)

Infectious diseases

Foreign pathogens have specific tropism to different areas of the body.

Some viruses and bacteria can bind to receptors located on neurons to wreak havoc on the nerve tissue. Examples of these viral infections include herpes simplex virus (HSV), varicella-zoster virus (VZV), chickenpox, Epstein-Barr virus (EBV), and shingles. (26)

As for bacterial infections, Lyme disease can cause extended nerve damage and peripheral pain if left untreated. (27)

Autoimmune diseases

Autoimmune diseases refer to a group of pathologies where the body’s immune system attacks self-tissues, such as muscles, bones, cartilage, and nerves.

Conditions like rheumatoid arthritis and systemic lupus erythematosus are notoriously known to damage the nerves and cause painful and tingling sensations. (28)

Other ailments that lead to chronic inflammation could also precipitate peripheral neuropathy by damaging the myelin sheaths of the nerves.

Injury

Physical trauma damages the nerves directly by sheer pressure.

Car accidents, fractures, falls, immobilization (e.g., being bedridden), and external pressure to the limb are common causes of peripheral neuropathy. (29)

Iatrogenic peripheral neuropathy*

The final cause of peripheral neuropathy on our list is the iatrogenic type, which is the result of certain pharmacological drugs: (30)

• Antibiotics (e.g., chloramphenicol, chloroquine, fluoroquinolones, metronidazole)
• Anti-neoplastic drugs (e.g., cisplatin)
• Antihypertensive drugs (e.g., amiodarone)
• Anticonvulsants (e.g., phenytoin)

Similar to other medical conditions, the diagnosis of peripheral neuropathy is a multi-step process that starts with taking your history.

Once you inform your doctor about the specific characteristics of the pain, and if you have other preexisting medical conditions, he/she will perform a thorough physical examination to assess the degree, location, and pattern of the pain.

The final step to diagnosing peripheral neuropathy involves paraclinical tests (e.g., blood tests, imaging).

For instance, if your doctor suspects that nutritional deficiencies are causing your pain, blood tests will inspect this theory. Additionally, blood sugar and thyroid hormone testing will reveal diabetes and thyroid pathologies.

As for imaging tests, CT scans or MRIs are quite sensitive at detecting any abnormalities surrounding the affected nerve, including fluid retention, herniation, and tumors. (31)

Other tests include:

Nerve tissue biopsy

This is a minor procedure that involves studying the nerve tissue under the microscope to identify any revealing pathological features. (32)

Electromyography

Electromyography, or EMG, analyzes the electrical patterns moving through the muscles during gentle contraction.

Your doctor will place a tiny electrode (needle-like object) and ask you to move your muscles. The EMG will then record the electrical activity inside the muscle, which may reveal certain illnesses (e.g., Duchene myopathy). (33)

The treatment of peripheral neuropathy is highly dependent on the underlying disease.

For instance, if diabetes is causing your pain, the doctor will change your anti-diabetic medications and recommend a few lifestyle modifications to control it. Another example would be vitamin deficiencies, which are easily corrected with supplementation.

However, many treatments are beneficial regardless of the underlying disorders, including:

Painkillers

The first-line treatment is acetaminophen (Tylenol), which is effective with mild cases of peripheral neuropathy. Non-Steroidal Anti-Inflammatory Drugs (e.g., ibuprofen, aspirin) can also be used. (34)

Unfortunately, these drugs carry some serious side effects if you take them for a long time or in large doses. (35)

The next generation of drugs includes more powerful analgesics, such as narcotics, antiepileptic drugs, and antidepressants. (36)

Examples include tramadol, gabapentin, pregabalin (Lyrica®), amitriptyline, and duloxetine.

Plasmaphereses

Plasmapheresis involves the filtration of blood from the antibodies that may be triggering an inflammatory response. (37)

Transcutaneous electronic nerve stimulation (TENS)

TENS is a treatment that only works for a specific group of patients. (38)

During TENS, the doctor places several electrodes around the skin to disrupt the pain signals sent by the damaged nerve. (39)

Lifestyle modifications

This is perhaps the vastest treatment approach to peripheral neuropathy.

People often report pain relief after:

• Chiropractic care (40)
• Message therapy (41)
• Cubbing therapy* (42)
• Mindfulness (e.g., yoga, meditation) (43)
• Moderate exercise (44)
• Reducing the intake of alcohol (45)
• Ceasing smoking (46)

Other beneficial tips to control peripheral neuropathy include wearing protective shoes, checking the temperature of the bath with your elbow before getting inside, and avoiding static positions for too long.

Peripheral neuropathy is an extremely common condition, especially among older adults with chronic illnesses, such as diabetes.

The complex pathophysiology and gradual worsening of this disease make it challenging to manage for both patients and their physicians.

Hopefully, this article helped you grasp the basics of peripheral neuropathy; however, if you still have any questions, please don’t hesitate to ask in the comment section below or reach out to us by clicking on this link (insert the link of contact us page).

1-Collaborators, G. B. (2015). of DS 2013. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 386(9995), 743-800. Link

2-Megari, K. (2013). Quality of life in chronic disease patients. Health psychology research, 1(3). Link

3-Richard, H. (2002). AC Peripheral neuropathy. BMJ, 23, 466-469.Link

4-Hammi, C., & Yeung, B. (2019). Neuropathy. Link

5- Pachman, D. R., Watson, J. C., Lustberg, M. B., Wagner-Johnston, N. D., Chan, A., Broadfield, L., … & Paice, J. (2014). Management options for established chemotherapy-induced peripheral neuropathy. Supportive Care in Cancer, 22(8), 2281-2295. Link

6- Hammi, C., & Yeung, B. (2019). Neuropathy. Link

7- Padua, L., Coraci, D., Erra, C., Pazzaglia, C., Paolasso, I., Loreti, C., … & Hobson-Webb, L. D. (2016). Carpal tunnel syndrome: clinical features, diagnosis, and management. The Lancet Neurology, 15(12), 1273-1284. Link

8- NIoNDa, S. (2014). Peripheral Neuropathy Fact Sheet. Accessed May, 14, 2014. Link

9- Nobile-Orazio, E. (2001). Multifocal motor neuropathy. Journal of neuroimmunology, 115(1-2), 4-18. Link

10- Jones, R. A., Harrison, C., Eaton, S. L., Hurtado, M. L., Graham, L. C., Alkhammash, L., … & Simmen, M. W. (2017). Cellular and molecular anatomy of the human neuromuscular junction. Cell reports, 21(9), 2348-2356. Link

11- Streckmann, F., Lehmann, H. C., Balke, M., Schenk, A., Oberste, M., Heller, A., … & Baumann, F. T. (2019). Sensorimotor training and whole-body vibration training have the potential to reduce motor and sensory symptoms of chemotherapy-induced peripheral neuropathy—a randomized controlled pilot trial. Supportive Care in Cancer, 27(7), 2471-2478. Link

12- Reeh, P. W. (1986). Sensory receptors in mammalian skin in an in vitro preparation. Neuroscience letters, 66(2), 141-146. Link

13- Mold, J. W., Vesely, S. K., Keyl, B. A., Schenk, J. B., & Roberts, M. (2004). The prevalence, predictors, and consequences of peripheral sensory neuropathy in older patients. The Journal of the American Board of Family Practice, 17(5), 309-318. Link

14- Johnson, B. K. (2018). Physiology of the Autonomic Nervous System. In Basic Sciences in Anesthesia (pp. 355-364). Springer, Cham. Link

15- Goldberger, J. J., Arora, R., Buckley, U., & Shivkumar, K. (2019). Autonomic nervous system dysfunction: JACC focus seminar. Journal of the American College of Cardiology, 73(10), 1189-1206. Link

16- Klein, C. J., Duan, X., & Shy, M. E. (2013). Inherited neuropathies: clinical overview and update. Muscle & nerve, 48(4), 604-622. Link

17- Bansal, V., Kalita, J., & Misra, U. K. (2006). Diabetic neuropathy. Postgraduate medical journal, 82(964), 95-100. Link

18- Liu, X., Xu, Y., An, M., & Zeng, Q. (2019). The risk factors for diabetic peripheral neuropathy: A meta-analysis. PloS one, 14(2), e0212574. Link

19-Gkogkolou, P., & Böhm, M. (2012). Advanced glycation end products: key players in skin aging?. Dermato-endocrinology, 4(3), 259-270. Link

20-Moorthi, R. N., Doshi, S., Fried, L. F., Moe, S. M., Sarnak, M. J., Satterfield, S., … & Newman, A. B. (2019). Chronic kidney disease and peripheral nerve function in the health, aging and body composition study. Nephrology Dialysis Transplantation, 34(4), 625-632. Link

21, 22-Dick, D. J., Lane, R. J., Nogues, M. A., & Fawcett, P. R. (1983). Polyneuropathy in hypothyroidism. Postgraduate medical journal, 59(694), 518-519. Link

23-Hammond, N., Wang, Y., Dimachkie, M., & Barohn, R. (2013). Nutritional neuropathies. Neurologic clinics, 31(2), 477. Link

24-Mellion, M., Gilchrist, J. M., & De La Monte, S. (2011). Alcohol‐related peripheral neuropathy: nutritional, toxic, or both?. Muscle & nerve, 43(3), 309-316. Link

25-Fullerton, P. M. (1969). Toxic Chemicals and Peripheral Neuropathy: Toxic Chemicals and Peripheral Neuropathy: Clinical and Epidemiological Features. Link

26-Brizzi, K. T., & Lyons, J. L. (2014). Peripheral nervous system manifestations of infectious diseases. The Neurohospitalist, 4(4), 230-240. Link

27-Wormser, G. P., Strle, F., Shapiro, E. D., Dattwyler, R. J., & Auwaerter, P. G. (2017). A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease. Diagnostic microbiology and infectious disease, 87(2), 163-167. Link

28-Cojocaru, I. M., Cojocaru, M., Silosi, I., & Vrabie, C. D. (2014). Peripheral nervous system manifestations in systemic autoimmune diseases. Mædica, 9(3), 289. Link

29-Menorca, R. M., Fussell, T. S., & Elfar, J. C. (2013). Peripheral nerve trauma: mechanisms of injury and recovery. Hand clinics, 29(3), 317. Link

30-Jones, M. R., Urits, I., Wolf, J., Corrigan, D., Colburn, L., Peterson, E., … & Viswanath, O. (2020). Drug-Induced Peripheral Neuropathy: A Narrative Review. Current Clinical Pharmacology, 15(1), 38-48. Link

31-Rangavajla, G., Mokarram, N., Masoodzadehgan, N., Pai, S. B., & Bellamkonda, R. V. (2014). Noninvasive imaging of peripheral nerves. Cells Tissues Organs, 200(1), 69-77. Link

32-Weis, J., Brandner, S., Lammens, M., Sommer, C., & Vallat, J. M. (2012). Processing of nerve biopsies: a practical guide for neuropathologists. Clinical neuropathology, 31(1), 7. Link

33-Misra, U. K., Kalita, J., & Nair, P. P. (2008). Diagnostic approach to peripheral neuropathy. Annals of Indian Academy of Neurology, 11(2), 89. Link

34, 36-Fornasari, D. (2017). Pharmacotherapy for neuropathic pain: a review. Pain and therapy, 6(1), 25-33. Link

35-Ghlichloo, I., & Gerriets, V. (2019). Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Link

37- Cortese, I., Chaudhry, V., So, Y. T., Cantor, F., Cornblath, D. R., & Rae-Grant, A. (2011). Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 76(3), 294-300. Link

38, 39- Gibson, W., Wand, B. M., & O’Connell, N. E. (2017). Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults. Cochrane Database of Systematic Reviews, (9). Link

40- Onifer, S. M., Sozio, R. S., DiCarlo, D. M., Li, Q., Donahue, R. R., Taylor, B. K., & Long, C. R. (2018). Spinal manipulative therapy reduces peripheral neuropathic pain in the rat. NeuroReport, 29(3), 191. Link

41- Chatchawan, U., Eungpinichpong, W., Plandee, P., & Yamauchi, J. (2015). Effects of Thai foot massage on balance performance in diabetic patients with peripheral neuropathy: a randomized parallel-controlled trial. Medical science monitor basic research, 21, 68. Link

42- Dimitrova, A., Murchison, C., & Oken, B. (2017). Acupuncture for the treatment of peripheral neuropathy: a systematic review and meta-analysis. The Journal of Alternative and Complementary Medicine, 23(3), 164-179. Link

43- Teixeira, E. (2010). The effect of mindfulness meditation on painful diabetic peripheral neuropathy in adults older than 50 years. Holistic nursing practice, 24(5), 277-283. Link

44- Dobson, J. L., McMillan, J., & Li, L. (2014). Benefits of exercise intervention in reducing neuropathic pain. Frontiers in cellular neuroscience, 8, 102. Link

45- Chopra, K., & Tiwari, V. (2012). Alcoholic neuropathy: possible mechanisms and future treatment possibilities. British journal of clinical pharmacology, 73(3), 348-362. Link

46- Clair, C., Cohen, M. J., Eichler, F., Selby, K. J., & Rigotti, N. A. (2015). The effect of cigarette smoking on diabetic peripheral neuropathy: a systematic review and meta-analysis. Journal of general internal medicine, 30(8), 1193-1203. Link