Man’s Best Friends May Help Us Manage Pain In People

In Brief

  • Phantom limb pain (PLP) is a neuropathic pain felt by amputees.
  • Companion animals may serve as good models for understanding PLP.
  • Research is currently being conducted utilizing the connections between animals and humans to combat neuropathic pain and manage PLP

According to the National Limb Loss Resource Center, 185,000 Americans have limbs amputated each year. This means, on average, between 300 to 500 appendages are removed each and every day. In amputees, pain seemingly coming from a missing limb occurs in severe ghost-like outbursts and can be stimulated by something as minute as the touch of a feather.

For about 80% of amputees worldwide, these sensations are real and often excruciating. This type of pain, called phantom limb pain (PLP), is neuropathic. This means it occurs when an injury or disease that affects the sensory nervous system causes the brain to misinterpret reality. Amputees can experience scratching, pinching, cramping and throbbing in their absent limbs. Such mysterious sensations are difficult to understand and treat.

Could our canine or feline friends help derive an answer to the perplexing issue of PLP management?

Companion animals and humans have similar nervous systems, specifically the motor and sensory cortices within their brains. These regions provide a neurological map of the body. Studies have shown that dog and human neurons react similarly in response to an amputation. In both species, when a body part is amputated, the neuron signals that control motion and feeling in that region are interrupted. But in some instances, the brain’s inherent plasticity provides an opportunity for neighboring neurons to expand and take over. For example, if an individual’s hand is amputated, neurons in surrounding regions, such as those that control the elbow, may adopt some of these neurons and reassign them to the elbow. The extent of this neural reorganization has been linked to the severity of PLP.

These are images of the brain’s activity while an individual moves their fingers. The bottom two brains show the activity of two individual with a forearm amputation. Courtesy: eLife Sciences, Revealing the Neural Fingerprints of a Missing Hand, 28 Sept. 2016.

Unfortunately, we can’t simply ask our pets how they’re feeling, so how do we know if animals experience PLP? This language barrier makes it difficult for veterinarians to recognize and treat animals’ pain. In fact, it was not until the 1990s that many veterinarians began accepting the concept that animals feel pain the same way humans do.

In 2007, Bradley O’Hagan, BVSc, an independent veterinary professional and consultant, observed and reported on the PLP phenomenon in companion animals. Dr. O’Hagan recognized PLP after performing a hind limb amputation on a 2-year-old cat who “walked holding the stump in the air as though trying to shake the amputated leg.” He found his patient could barely walk before shaking his stump and falling over. Shortly after publishing his paper, Dr. O’Hagan was presented with a dog with similar clinical signs. He concludes that behavioral issues and consistent irritation indicated the cat and dog both felt as though their legs were still there, which parallels symptoms of PLP in humans.

However, is this observation enough to suggest companion animals may be good models for human PLP research? Dr. O’Hagan acknowledges that some veterinarians argue it is possible the “nature of neuropathic pain may mean that it is recognized as a behavioral problem in non-verbal patients like animals, and not really attributed to pain.” They attribute yelps, flinches, or snarls from our four-legged, or rather three-legged friends, not to pain, but rather to the disagreeable nature of the animal.

There is evidence that post-amputation pain research can mutually benefit animals and humans. For example, Alexis Nahama, DVM, president of Ark Animal Health, and his colleagues believe that companion animals are a good model for PLP. The company is developing resiniferatoxin (RTX), a one-time, non-opioid injection as a therapeutic solution against intractable pain like neuropathic or chronic articular pain in animals. Using this treatment could potentially eliminate or at least significantly reduce the need for daily pain medications.

In an ongoing trial, nine felines were successfully treated with the RTX injection. These cats had previously displayed behavioral changes including aggressive behavior as a result of long-term pain that persisted for months to years after declawing. Dr. Nahama discourages pet owners from considering such a procedure with their pets, highlighting that it is not a cosmetic or a minor surgery. He describes it as “the amputation of the last digits of every single finger of the front paws.”

Sorrento Therapeutics, the parent company of Ark Animal Health, found the cat study and additional work in dogs so encouraging they decided to explore the same direct to nerve application approach in human clinical trials. The physiological similarities are being leveraged to develop sophisticated pain management that benefits several species.

There are currently 2.1 million people living with limb loss in the USA, and that number is expected to double by 2050. We’re hopeful by that time, those who have lost a limb will have a greatly improved quality of life thanks to our furry three and four-legged friends’ participation in multi-species clinical trials.

Content Experts

Dr. Alexis Nahama, DVM, is the senior vice president of corporate development at Sorrento Therapeutics and President of Ark Animal Health. Dr. Nahama got his veterinary degree in statistics and experimental methodology certification at L’Ecole Nationale Vétérinaire d’Alfort, France. As both a businessman and a scientist, Dr. Nahama provided his unique perspective to this work.

Dr. Bradley O’Hagan is currently an independent veterinary professional and consultant with a diverse range of experience in clinical practice, marketing, pharmaceutical R&D, technical support, and volunteering for international development. He was the first to record potential PLP in companion animals. Dr. O’Hagan earned his BVS honors at The University of Queensland, Australia in Veterinary Science and his Master’s at The University of Edinburgh..


Citations

  1. Animal Welfare Forum. “What Is Pain?” Animal Welfare Forum: Pain Management, 14 Oct. 2001, Chicago, Illinois. American Veterinary Medical Association, AVMA, 2001, ebusiness.avma.org/Files/ProductDownloads/2001_pain_management.pdf.
  2. Chen, Albert et al. “Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation.” NeuroImage. Clinical vol. 3 498-506. 11 Oct. 2013, doi:10.1016/j.nicl.2013.10.001
  3. Collins, Kassondra L et al. “A review of current theories and treatments for phantom limb pain.” The Journal of clinical investigation vol. 128,6 (2018): 2168-2176. doi:10.1172/JCI94003
  4. Chung, Kevin C et al. “A cost-utility analysis of amputation versus salvage for Gustilo type IIIB and IIIC open tibial fractures.” Plastic and reconstructive surgery vol. 124,6 (2009): 1965-73. doi:10.1097/PRS.0b013e3181bcf156
  5. Epstein, Mark E. “Neuropathic Pain in Veterinary Patients, Part 1.” Veterinary News, 1 Jan. 2012, veterinarynews.dvm360.com/neuropathic-pain-veterinary-patients-part-1.
  6. Karl, Anke, et al. “Reorganization of Motor and Somatosensory Cortex in Upper Extremity Amputees with Phantom Limb Pain.” The Journal of Neuroscience, 15 May 2001. The Journal of Neuroscience, doi:10.1523/JNEUROSCI.21-10-03609.2001.
  7. Kenhub. “Motor and Sensory Cortical Homunculus.” Kenhub, 2019, www.kenhub.com/en/videos/cortical-homunculi?utm_source=youtube&utm_medium=video&utm_campaign=motor-and-sensory-cortical-homunculus-preview&utm_content=endscreen.
  8. Kikkert, Sanne Kikkert, and James Kolasinski. “Revealing the neural fingerprints of a missing hand.” eLifeScience, 28 Sept. 2016. eLifeScience, doi:10.7554/ eLife.15292. Accessed 5 July 2020.
  9. Owings M, Kozak LJ, National Center for Health S. Ambulatory and Inpatient Procedures in the United States, 1996. Hyattsville, Md.: U.S. Dept. of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics; 1998.
  10. People With Amputations Speak Out. PDF ed.
  11. PetMD. “Pain from the Nervous System in Cats.” PetMD, edited by PetMD, www.petmd.com/cat/conditions/neurological/c_ct_neuropathic_pain?page=show.
  12. Robertson, Sheliah, BVMS. “Innovations in Analgesia.” PDF file, 2017.
  13. Sorrento Therapeutics, Inc. “Positive Feline Clinical Trial Outcome Motivates Sorrento Therapeutics to Accelerate Human IND Filing of Resiniferatoxin (RTX) for Prolonged Non-Opioid Control of Post-Amputation Neuropathic Pain.” Global Newswire, 10 June 2019, www.globenewswire.com/news-release/2019/06/10/1866190/0/en/Positive-Feline-Clinical-Trial-Outcome-Motivates-Sorrento-Therapeutics-to-Accelerate-Human-IND-Filing-of-Resiniferatoxin-RTX-for-Prolonged-Non-Opioid-Control-of-Post-Amputation-Neu.html.

Image Credits:

Chief Editor: Sophie Zhang

Creative Team Co-Managers: Macafie Bobo and Aparna Kumar

Story Image: Jim Newman


This article was written by Stephanie Ona. Stephanie and the cSw student editing team would like to thank Cathy Moldave for serving as a mentor on this story. Cathy Moldave is a freelance science and technology writer.

As always, before leaving a response to this article please view our Rules of Conduct. Thanks! -cSw Editorial Staff

Stephanie Ona

Author: Stephanie Ona

Hello, I’m Stephanie Ona from Morristown High School in New Jersey. I love creative writing and science, specifically behavioral neuroscience. The wonderful experience I had in the curiousSCIENCEwriters program showed me that it is possible to meld my two loves together. Outside of school, I am occupied in all sorts of activities including clubs, sports, work, and teaching. I hope to become a neurologist and help better the lives of others.

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