Why Does a Missing Limb Still Hurt?

A few weeks ago, my daughter reached up and touched a hot burner on the stove. She screamed and cried, but luckily pulled her hand away before there was any real damage. I ran to help her, washed her hand with cool water, applied some cool water and aloe, and put on a bandaid. As heartbreaking as it all was, it really puts into perspective the importance of pain. Pain caused her to pull back her hand rapidly, before it could get seriously burned, and alerted me that she needed help. Pain is an unpleasant sensory and emotional experience, but it has a real, survival-ensuring purpose.^[1] 

Except when it doesn’t.

Phantom limb pain is pain felt in an amputated limb - a limb that is no longer present.^[2,3] This pain serves no purpose, since there’s no danger to pull away from and no body part to protect from damage. Hundreds of thousands of amputations occur in the US each year - hundreds per day.^[4,5] In total, over 2.3 million people are living with an amputation, with rates skewed towards those living with poverty.^[4,6] For those under the age of 45, most amputations result from traumatic injuries (like car crashes).^[4] In contrast, among adults over 65, most amputations are a result of complications from vascular conditions, like diabetes or peripheral vascular disease.^[4] Although the limb is no longer present, phantom limb pain remains a significant challenge, affecting a majority of people with amputations.^[4]

To understand why phantom limb pain exists, we have to try to understand how pain works. To feel things in the world, long, specialized cells called neurons connect receptors in or near the skin to the brain, which processes and perceives sensations such as pain.^[1] Typically, these receptors respond to things like temperature, tissue damage, skin stretching, and inflammation.^[1] Sometimes, however, the neurons themselves are damaged, and signals get sent to the brain even without a receptor present.^[1] This is called neuropathic pain, a classic example of the pain mechanism not working as it should. It’s also part of the answer to what’s happening with phantom limb pain.^[1,7]

The other part of how pain works is in the brain and spinal cord, called the central nervous system. Pain signals come from neurons, but the central nervous system has enormous leeway in how it perceives them.^[1,7] As an example, when my daughter falls at the park, she looks around to find me. If I run over, panicking and hollering, “oh no, oh no, are you ok?!” she thinks it must be serious, cries, and feels more pain. If instead I give her a thumbs up and say “nice wipeout,” she does a cool pose, gives me a peace sign, and continues running with wild abandon. The parts of the central nervous system involved in phantom limb pain include the sensory and motor networks that sense the outside world and move muscles accordingly.^[7]

Phantom limb pain doesn’t affect everyone. The exact prevalence is unknown, but high-quality surveys show that around 63-64% of people with amputations have phantom limb pain.^[2] Factors associated with increased risk of developing phantom limb pain include:^[2,3]

• Lower-limb amputations
• Pain in the stump, also called residual limb pain
• Amputations closer to the trunk of the body (e.g. above the elbow vs at the wrist)
• Amputations due to vascular complications from diabetes
• Greater pre-amputation pain

Many of these factors are related: diabetes-related amputations tend to be on the lower limbs and are more likely to have pre-amputation pain, for example.

The experience of phantom limb pain is unique to each individual.^[3] People’s experiences vary in the quality, intensity, frequency, and severity of pain, and this can change over time.^[3] Because of this, and the dual nature of how pain works, phantom limb pain can be difficult to treat. A panel of experts endorsed a handful of treatments targeting phantom limb pain, including:^[7]

• Mirror therapy, which uses a reflection of the intact limb to give visual feedback and convince the brain to stop perceiving pain
• Graded motor therapy, a three-step program which includes mirror therapy as a step
• Cognitive behavior therapy, a form of psychotherapy
• Functional prosthesis, which performs functions like the missing limb, not just a cosmetic replacement
• Virtual reality (VR) training, which can act like a more interactive version of mirror therapy
• Sensory discrimination training, which applies different textures near the amputation site
• Amitriptyline, an antidepressant prescribed for neuropathic pain

Other than this small handful of endorsed treatments, surveys have found that doctors prescribe dozens of different treatments.^[3,7] Unfortunately, few treatments have undergone clinical trials to show effectiveness for phantom limb pain, and those that have rarely outperform placebo, especially medical treatments.^[3,7] A big part of this is that a placebo (a treatment with no active ingredient) can be highly effective in treating pain, making successful trials even harder.^[8] This means we need high-quality studies to evaluate treatment options, including new ones.

One relatively new treatment option is cryoneurolysis. This method uses extreme cold (close to negative 100 degrees Fahrenheit) to temporarily destroy part of the nerve sending signals to the brain.^[9] The idea is to freeze a neuron causing neuropathy to provide weeks or months of relief in a low-risk manner.^[9] Unfortunately, like many other treatments, cryoneurolysis has not shown effectiveness in clinical trials. If scientists find strong clinical evidence of success for this and other methods, phantom limb pain may become a hot topic for keeping pain useful.

Creative Director Benton Lowey-Ball, MWC, BS, BFA

References:

[1] Kandel ER, Schwartz JH, Jessell TM, Kupfermann I, Iversen S, editors. Principles of neural science. 4th ed. New York: McGraw-Hill; 2000. p. 472-490.

[2] Limakatso K, Bedwell GJ, Madden VJ, Parker R. The prevalence and risk factors for phantom limb pain in people with amputations: a systematic review and meta-analysis. PloS one. 2020 Oct 14;15(10):e0240431. https://doi.org/10.1371/journal.pone.0240431

[3] Schone HR, Baker CI, Katz J, Nikolajsen L, Limakatso K, Flor H, Makin TR. Making sense of phantom limb pain. Journal of Neurology, Neurosurgery & Psychiatry. 2022 Aug;93(8):833-43. https://doi.org/10.1136/jnnp-2021-328428

[4] Ziegler-Graham PK, MacKenzie PE, Ephraim MP, Travison PT, Brookmeyer PR. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Archives of physical medicine and rehabilitation. 2008 Mar 1;89(3):422-9. https://doi.org/10.1016/j.apmr.2007.11.005

[5] Rivera JA, Churovich K, Anderson AB, Potter BK. Estimating recent US limb loss prevalence and updating future projections. Archives of Rehabilitation Research and Clinical Translation. 2024 Dec 1;6(4):100376. https://doi.org/10.1016/j.arrct.2024.100376

[6] Rivera JA, Churovich K, Anderson AB, Potter BK. Estimating recent US limb loss prevalence and updating future projections. Archives of Rehabilitation Research and Clinical Translation. 2024 Dec 1;6(4):100376. https://doi.org/10.1016/j.arrct.2024.100376

[7] Limakatso K, Parker R. Treatment recommendations for phantom limb pain in people with amputations: an expert consensus Delphi study. PM&R. 2021 Nov;13(11):1216-26. https://doi.org/10.1002/pmrj.12556

[8] Colloca L. The placebo effect in pain therapies. Annual review of pharmacology and toxicology. 2019 Jan 6;59(1):191-211. https://doi.org/10.1146/annurev-pharmtox-010818-021542

[9] Biel E, Aroke EN, Maye J, Zhang SJ. The applications of cryoneurolysis for acute and chronic pain management. Pain Practice. 2023 Feb;23(2):204-15. https://doi.org/10.1111/papr.13182