Can We Engineer Pain Out of the Human Body?

Can We Engineer Pain Out of the Human Body?

One of the most poorly managed parts of medicine is pain, which is ironic for something that is such a universal experience. From post-surgical discomfort to chronic neuropathic pain, millions of patients live with pain that is either inadequately treated or treated at a significant cost to quality of life. For decades, pain has been viewed primarily as a symptom, something to be chemically suppressed. However, as chronic pain emerges as a condition in itself, this view is beginning to change.

Pain isn’t just a physical sensation but rather a complex biological process constructed by the nervous system. It’s caused by peripheral receptors, spinal circuits and distributed brain networks all working together but is also influenced by factors such as memory and expectation. The complicated nature of how pain is created raises an important question: if pain is produced by organised neural processes, could it be modified, redirected or even engineered out of the system entirely? And if it can, should it be?

Technology such as neuromodulation, brain-computer interfaces, genetic targeting of nociceptors and computational models of neural signalling already allow us to alter how pain is generated, transmitted and perceived. These don’t just mask pain, they intervene in the biological systems that create it. However, rare conditions in which pain is absent entirely, reveal that eliminating pain is not inherently beneficial and even dangerous.

In this article, I explore whether pain can be viewed not only as a symptom to be managed, but also as a biological system that can be understood and controlled. By examining where pain arises in the body, how it can be manipulated and what happens when it disappears altogether, I aim to analyse how far biomedical engineering can push the boundaries of pain treatment and what this might mean for the future of medicine.

1. Pain as a Protective Mechanism

Pain isn’t something that randomly developed in our bodies, nor is it just an inconvenience that can be ignored. We feel it because it is useful. Think of it as a biological warning system, it alerts us to potential or actual tissue damage and then initiates behaviours that minimize the risk of further injury or damage. Pain-driven responses such as: immediately moving away from a hot surface, avoiding sharp objects or protecting and partially immobilising an injured limb, are all behaviours that increase our likelihood of survival.

Specialised sensory neurons, called nociceptors, detect extreme mechanical, thermal or chemical stimuli and relay this information to the central nervous system causing us to feel pain. However, unlike other parallel sensory input, these signals are prioritised by our brain ensuring that potential threats receive more attention (Tracey and Mantyh, 2007). Over many centuries and many evolutionary cycles, organisms that were able to quickly detect and react to damaging stimuli could survive longer and therefore reproduce more, allowing for these pain pathways to be conserved and refined.

Not only does pain trigger immediate reflexes, but it also influences future behaviour. For example, if someone were to cut their finger with a knife, the next time they use a knife they would be more careful and keep their fingers further away from the blade. By experiencing pain, the body learns and remembers painful experiences which reduces the likelihood of repeating dangerous actions and allows pain to effectively act as a long-term protective mechanism. In this way, pain isn’t just a signal but rather part of a broader system that combines perception, decision making and behaviour (Wood et al, 2020).

The necessity of pain is especially evident when it’s absent, such as in rare genetic conditions. Individuals who can’t feel pain show that without these signals injuries often go unnoticed, infections and disease can progress without being checked and life-threatening damage can occur without warning. Cases like these show that pain isn’t inherently pathological but rather an essential defence system that only becomes a medical problem when its regulation fails.

2. Acute vs. Chronic Pain

As discussed above, pain is an essential survival mechanism, however, not all pain serves as protection. Medically, there is a clear difference between acute and chronic pain as the mechanisms and medical implications of each are fundamentally different. Acute pain is usually short term and directly linked to tissue damage or inflammation - it arises in response to injury, surgery or infection and resolves itself as the tissue heals. This type of pain encourages rest, moving away from harmful stimuli and behaviours that promote recovery. Meanwhile, chronic pain continues long after the initial injury heals meaning it could last for months or even years. Most commonly, there is no longer any clear tissue damage which could justify the continued pain, instead, the nervous system itself becomes dysfunctional. Research shows that continued pain can cause long-term changes in neural signalling - this process is called central sensitisation and it happens when neurons in the spinal cord and brain become hyper-responsive amplifying pain signals disproportionately (Woolf, 2011). A result of this is increased sensitivity to pain to the point where non-painful stimuli may also be perceived as painful and painful stimuli feel more intense.

This highlights the shift between pain as a useful signal and protective mechanism to pain as a disease. Chronic pain is being increasingly recognised not only as a symptom but also as a disorder of the nervous system in itself. For example, the International Association for the Study of Pain (IASP) now classifies pain as its own disease in the ICD-11 (International Classification of Diseases, 11th Revision) in accordance with growing evidence that it’s maintained by dysfunctional neuroplasticity rather than a current injury (Treede et al. 2019).

From a biomedical standpoint, the distinction between the two is crucial. Acute pain can often be effectively managed with common pharmacological approaches, whereas chronic pain remains resistant to many of these standard treatments. By understanding how and why pain transitions from a protective response to a self-sustaining pathological state is essential to not only improve pain management, but also identify where biomedical interventions might interrupt, modulate or reverse these modified neural processes.  

3. Pain as a Constructed Nervous System Disorder

As pain becomes chronic, it can’t be explained by ongoing tissue damage. Instead, it exposes dysfunctional changes within the nervous system leading to a growing consensus that chronic pain should be understood as a disorder of neural processing rather than a constant warning signal. Continued pain alters synaptic strength, neural excitability and network connectivity in both the spinal cord and brain which allows pain to be generated even in the absence of tissue damage (Woolf and Salter, 2000). 

These changes are driven by the same system that underlies learning and memory - neural plasticity. Plasticity is essential for adaptation, however, in the context of pain it can become the cause. Repeated nociceptive input increases the ‘gain’ of gain pathways which make them more sensitive and less selective, which over time allows the nervous system to learn pain and reinforce it through altered circuits and sustained network activity (Woolf, 2011). This explains the persistence of chronic pain despite healing, and why it can be resistant to conventional treatments that target the original injury as opposed to the altered neural state of the patient.

Crucially, pain isn’t generated in a single location within the brain. Modern neuroimaging techniques have shown that pain perception emerges from the coordinated activity of multiple brain regions such as the: thalamus, somatosensory cortex, insula, anterior cingulate cortex and prefrontal cortex (Apkarian et al, 2005). These regions are responsible for both processing the sensory intensity of pain as well as its emotional significance and contextual meaning. As a result, pain is affected by attention, expectation, mood and previous experience. These factors can amplify or reduce the perceived intensity of the same physical stimulus. All of this evidence supports the fact that pain is a constructed experience, one that’s assembled by the brain rather than passively reviewed from the body. Cognitive processes such as belief or anticipation can also significantly alter how pain is perceived - as demonstrated by the placebo effect - where pain levels may differ despite an identical sensory input (Tracey, 2010). In this way, pain is more of a reflection of the brain’s interpretation of a threat rather than a direct measure of damage.

Through understanding pain as a dynamic, distributed and learned process we can begin to understand how to effectively treat it. If pain arises from altered neural networks, not just damaged tissue alone, then effective treatment must be able to target these networks directly. This perspective lays the foundation for biomedical approaches that are able to recalibrate the neural systems causing pain instead of merely chemically suppressing it.

4. What does the Absence of Pain Reveal?

One of the strongest pieces of evidence that pain is a constructed biological process comes from genetic conditions where pain perception is entirely absent. Congenital Sensitivity to Pain (CIP), also sometimes called congenital analgesia, is a group of inherited disorders with which an individual is born unable to feel physical pain despite having otherwise working sensory systems (Cox et al, 2006).

If you think about it, this may seem like an advantage at first, however, medical observations actually reveal the opposite. Individuals with CIP frequently sustain severe injuries, fractures, infections and burns as their main protection signal - pain - is missing. It’s not uncommon for these patients to have lowered life expectancy caused by repeated unnoticed trauma which highlights how pain plays a critical role in survival - it isn’t just an unpleasant sensation (Indo, 2015).

In terms of engineering, CIP is particularly revealing as it often arises from single-gene mutations which allows researchers to pinpoint the specific molecular components required for pain generation. One of the most well-studied cases involves mutations in the SCN9A gene which is responsible for encoding the voltage-gated sodium channel Nav1.7. This channel is crucial for initiating and transmitting action potentials in nociceptive neurons. When Nav1.7 isn’t functional, pain signals fail to reach the central nervous system despite the rest of the sensory pathways remaining largely intact (Cox et al, 2006; Goldberg et al, 2007).

Other forms of CIP involve mutations affecting nerve growth factor signalling (NTRK1) which leads to the improper development of nociceptive neurons (Indo, 2015). The findings from this research show that pain isn’t an inevitable by-product of having a nervous system, but rather a culmination of specific engineerable biological components that integrate across molecular, cellular and network pathways. Additionally, CIP doesn’t imply a lack of awareness or consciousness as individuals with this condition can still feel touch, temperature (to a certain degree), pressure and emotional distress. This dissociation indicates that pain is a distinct neural construct that can be separated from other sensory and cognitive processes, or more simply, the brain doesn’t require pain to be conscious but pain requires precise pathways to be generated.

These insights have significant effects on medicine. By understanding, fundamentally, exactly how pain can be selectively removed through the disruption of specific neural mechanisms, we essentially gain a template for designing targeted pain-relieving therapies. Instead of broadly suppressing neural activity, future treatments may precisely control ion channels, signalling pathways or networks involved in the synthesis of pain, reducing its effects without compromising motor function or awareness. 

5. Genetic and Molecular Engineering of Pain

Studies on patients with CIP and their pain insensitive phenotype provide information on how nociception is generated, however, the challenge now is to turn this knowledge into a safe and controlled treatment. Genetic and molecular engineers attempt to intervene during the earliest stages of pain processing by targeting the genes and proteins that create nociceptive signals, rather than suppressing already formulated pain.

Instead of focusing on naturally occurring mutations, current research is based on selective gene modulation. Techniques such as: CRISPR based editing, RNA interference and antisense oligonucleotides allow us to edit pain related genes within groups of sensory neurons. These methods can be targeted to peripheral nociceptors which avoids any widespread effects on the central nervous system (Ovsepian & Waxman, 2023; Moreno et al, 2021). During trials on animals, these approaches have been able to produce consistent reductions in pain related behaviour without compromising sensation, movement or recognition which highlights them as a more precise alternative to systemic analgesics.

From a design point of view, the challenge lies in the degree of permanence that these interventions have. Although permanent gene edits may offer long lasting relief for severe and treatment resistant pain, they also reduce adaptability and increase risk if side effects occur. Consequently, many researchers are trying to prioritise reversible molecular treatments, such as RNA based silencing which allows pain pathways to be adjusted dynamically with the fluctuating nature of pain itself (Bajan & Hutvagner, 2020). Although reversible, the reversibility of these treatments functions more as a safety mechanism rather than a limitation.

Safety is still one of the largest constraints of genetic pain engineering due to its protective role, where excessively suppressing it risks similar complications as those with CIP. Therefore, the goal isn’t actually to eliminate pain but rather to selectively reduce pathological pain - such as pain caused by inflammation, nerve injury or maladaptive plasticity. To achieve this, we require molecular specificity, temporal control and integration with higher level neural regulation. Overall, the goal from a genetic and molecular standpoint is to move away from pain management as total suppression and more towards designing the way that specific pain signals are synthesised.

6. Why Isn’t Pharmacology Enough?

For a large part of modern medicine, pharmacology has been the most commonly used tool for altering brain function. Drugs such as: anaesthetics, antidepressants, antipsychotics and analgesics (pain-killers) have allowed us to suppress, stabilise or enhance neural activity chemically. These interventions have been essential in treating neurological and psychiatric disease, however, they have one fundamental limitation - they treat pain as a chemical problem not as a system.

Most analgesic drugs act broadly across the whole nervous system. For example, opioids reduce the perception of pain by binding to μ-opioid receptors in the brain and spinal cord. Although this reduces nociceptive signalling, it also affects other biological processes like respiration, cognition and reward pathways (Volkow & McLellan, 2016). Their lack of specificity means that pain relief often comes at the cost of sedation, addiction or respiratory depression - an overall inefficient solution as we are altering an entire system to influence a single output.

The limits of pharmacology are further tested by chronic pain, which unlike acute pain, isn’t simply a prolonged nociceptive signal (as mentioned previously) but rather a maladaptive state involving cortical reorganisation, altered synaptic plasticity and irregular network connectivity (Apkarian et al, 2009). In cases like these, simply increasing drug dosage has no effect on resolving the underlying problem as the pain no longer originates from an injury. Pharmacological approaches have limited success in reversing these extensive neural changes, which explains why many chronic pain patients experience limited relief.

Another major issue is that drugs can’t distinguish between pathological and protective pain. It’s an essential warning system but many drugs used to suppress it dampen both harmful and beneficial signals. Most analgesics work by reducing nociceptive signaling either at the peripheral level (eg. by inhibiting prostaglandin synthesis), at the spinal cord or by altering neurotransmitter activity in pain processing networks, instead of selectively targeting malfunctioning pain circuits (Basbaum et al, 2009). This is particularly harmful during long-term treatment as eliminating pain entirely can cause repercussions such as increased risk of injury, infection or tissue damage - the same risks that individuals with CIP have to manage.

From a progressive standpoint, pharmacology offers no direct insight into how pain is actually constructed by the nervous system. Chemical based treatments mask symptoms but don’t reveal much about the encoding and interpretation of pain signals across peripheral nerves, spinal pathways and cortical networks also provide little guidance for designing targeted or personal interventions.

These limitations have shifted biomedical engineering towards an approach that aims to treat pain as an information-processing problem rather than a chemical one. Technology such as: electrical neuromodulation, neural interfaces and computational models aim to disrupt specific points within pain pathways, allowing them to possibly alter pain selectively while preserving normal sensation. In this way, pharmacology remains as a helpful tool but it is no longer sufficient on its own to engineer pain out of the body.

7. Brain-Computer Interfaces and the Future of Pain Control

As pain isn’t just a sensory signal but also a perceptual and cognitive experience shaped by factors like attention, expectation and context, it is uniquely suited to intervention through brain-computer interfaces (BCIs). Rather than chemically trying to suppress nociceptive input, they aim to intercept or regulate pain-related neural activity. 

BCIs essentially rely on the fact that pain has identifiable neural patterns. Neuroimaging and electrophysiological studies have shown that the perception of pain involves coordinated activity across many different brain regions (Apkarian et al, 2005). Through invasive or non-invasive interfaces, these signals can be recorded and engineers can detect patterns associated with pain intensity and relief. 

As we continue to train and improve machine learning, we have also been able to significantly improve the ability of BCIs to decode these patterns with algorithms that have been trained on neural data even being able to predict pain ratings without verbal feedback with increasing accuracy (Wager et al, 2013; Woo et al, 2017). This is especially valuable for patients who are unable to communicate their pain, such as those under anaesthesia or with severe neurological impairment, as it opens the door for objective and personalised pain monitoring. 

BCIs also enable closed-loop pain modulation; a system where any neural activity that is associated with pain triggers focused stimulation which is meant to disrupt the maladaptive network dynamics. Experimental closed-loop neuromodulation has already shown its potential in chronic pain conditions, where stimulation of specific cortical or subcortical regions reduces pain perception more effectively than open-loop approaches (Shirvalkar et al, 2018). They are also much more precise than any drugs as they can adapt their stimulation in real time to most effectively treat fluctuations in pain.

BCIs can also be integrated with the spinal or peripheral interfaces within our bodies. Ones that are integrated with spinal cord stimulation systems can control ascending pain pathways without damaging or compromising normal sensory and motor function (Lam et al, 2023). Similarly, when integrated with the peripheral nervous system they are able to interrupt pain signals before they reach the central nervous system which basically creates a programmable filter between an injury and the pain that is perceived.

In addition, BCIs show that there is an element of cognition in pain. Neurofeedback-based systems can allow patients to actively alter their own brain activity by providing visual or audio representations of pain related neural signals. Studies have shown that, with some training, patients can alter activity in specific cortical regions of their brain thereby reducing pain and revealing a certain level of control that the brain has over it (deCharms et al, 2005). 

While technology like this is still largely experimental, it shows a shift in pain management from treating pain as a symptom and suppressing it chemically, to a process that can be measured, decoded and restructured by interacting with the nervous system. As these neural interfaces become more precise and most importantly safer, BCIs may become a part of future pain management where we don’t eliminate it entirely but rather minimise suffering strategically.

8. Ethics and the Future of Pain Management

While it’s generally positive that we are moving in the direction of being able to eliminate pain, there is an important ethical question as to how far we should intervene. As I mentioned previously, pain is not a system that came about accidentally, but rather a biological feedback system that protects us. All our attempts at engineering or intervening with pain happen at a very fragile ethical boundary where we must reduce suffering without dismantling the system that is necessary for survival.

As we have observed from individuals with CIP, life without the ability to feel pain isn’t ideal but rather detrimental to our life expectancy. Cases like these, show that removing pain entirely actually enhances our vulnerability and is therefore a constraint to the progression of pain management. Engineering the ability to control pain is fundamentally different from engineering the absence of pain. Our goal is not to fully block nociceptive signalling but rather to preserve beneficial and protective pain while selectively suppressing maladaptively caused pain, which is what we see in chronic pain disorders. To achieve this, interventions must be functionally precise so they can target specific circuits or ion channels as opposed to the neural network as a whole.

By looking at pain as an ‘editable’ process rather than a symptom, it also changes it’s role in medicine. If we are able to develop precision pain management, it will open the door to personalised treatments and therapies that are tailored to patient medical history and genetic background. This is specially relevant in fields such as post surgical recovery and long-term neurological disease where, now, pain is treated at the expense of quality of life as it affects abilities such as cognition and mobility. The future of pain management is intervening only when pain becomes maladaptive, rather than suppressing the whole system.

If you look at pain more broadly, its complexity in combining sensation, cognition, emotion and behaviour makes it an ideal condition to test and improve on evolving technology that is designed to interface with complex brain networks. The same technology that we use to decode and restructure pain may eventually be applied to conditions that involve mood, memory or motor control. In this way, pain management isn’t its own task but rather the beginning of how the medical field will interact with the nervous system in the near future.

To answer the initial question: can pain be engineered out of the human body? The short answer is no and it shouldn’t be. The longer answer would be that pain can be engineered with, through its measurement and control in ways that reduce suffering but don’t take away from its protective function or our nervous system as a whole.

Bibliography:

1. Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007 Aug 2;55(3):377-91. doi: 10.1016/j.neuron.2007.07.012. PMID: 17678852.

2. Wood, John & Stein, Christoph & Gaveriaux-Ruff, Claire. (2020). The Oxford Handbook of the Neurobiology of Pain.

3. Clifford J. Woolf, Central sensitization: Implications for the diagnosis and treatment of pain, PAIN, Volume 152, Issue 3, Supplement, 2011, Pages S2-S15, ISSN 0304-3959, https://doi.org/10.1016/j.pain.2010.09.030.

4. Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Korwisi B, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11). Pain. 2019 Jan;160(1):19-27. doi: 10.1097/j.pain.0000000000001384. PMID: 30586067.

5. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765. PMID: 10846153.

6. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;152(3 Suppl):S2-S15. doi: 10.1016/j.pain.2010.09.030. Epub 2010 Oct 18. PMID: 20961685; PMCID: PMC3268359.

7. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005 Aug;9(4):463-84. doi: 10.1016/j.ejpain.2004.11.001. Epub 2005 Jan 21. PMID: 15979027.

8. Tracey I. Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans. Nat Med. 2010 Nov;16(11):1277-83. doi: 10.1038/nm.2229. Epub 2010 Oct 14. PMID: 20948533.

9. Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006 Dec 14;444(7121):894-8. doi: 10.1038/nature05413. PMID: 17167479; PMCID: PMC7212082.

10. Indo Y. [Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis]. No To Hattatsu. 2015 May;47(3):173-80. Japanese. PMID: 26211335.

11. Ovsepian, S. V., & Waxman, S. G. (2023). Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors. Nature Reviews. Neuroscience, 24(4), 252–265. https://doi.org/10.1038/s41583-022-00673-7

12. Moreno, A. M., Alemán, F., Catroli, G. F., Hunt, M., Hu, M., Dailamy, A., Pla, A., Woller, S. A., Palmer, N., Parekh, U., McDonald, D., Roberts, A. J., Goodwill, V., Dryden, I., Hevner, R. F., Delay, L., Santos, G. G. D., Yaksh, T. L., & Mali, P. (2021). Long-lasting analgesia via targeted in situ repression of Na V 1.7 in mice. Science Translational Medicine, 13(584). https://doi.org/10.1126/scitranslmed.aay9056

13. Bajan, S., & Hutvagner, G. (2020). RNA-Based therapeutics: From antisense oligonucleotides to miRNAs. Cells, 9(1), 137. https://doi.org/10.3390/cells9010137

14. Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, Andria G, Toscano E, Kerdraon J, Bowsher D, Pimstone SN, Samuels ME, Sherrington R, Hayden MR. Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet. 2007 Apr;71(4):311-9. doi: 10.1111/j.1399-0004.2007.00790.x. PMID: 17470132.

15. Volkow ND, McLellan AT. Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. N Engl J Med. 2016 Mar 31;374(13):1253-63. doi: 10.1056/NEJMra1507771. PMID: 27028915.

16. A. Vania Apkarian, Marwan N. Baliki, Paul Y. Geha, Towards a theory of chronic pain, Progress in Neurobiology, Volume 87, Issue 2, 2009, Pages 81-97, ISSN 0301-0082 https://doi.org/10.1016/j.pneurobio.2008.09.018.

17. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009 Oct 16;139(2):267-84. doi: 10.1016/j.cell.2009.09.028. PMID: 19837031; PMCID: PMC2852643.

18. Wager, T. D., Atlas, L. Y., Lindquist, M. A., Roy, M., Woo, C., & Kross, E. (2013). An FMRI-Based neurologic signature of physical pain. New England Journal of Medicine, 368(15), 1388–1397. https://doi.org/10.1056/nejmoa1204471

19. Woo, C., Schmidt, L., Krishnan, A., Jepma, M., Roy, M., Lindquist, M. A., Atlas, L. Y., & Wager, T. D. (2017). Quantifying cerebral contributions to pain beyond nociception. Nature Communications, 8(1), 14211. https://doi.org/10.1038/ncomms14211

20. Shirvalkar, P., Veuthey, T. L., Dawes, H. E., & Chang, E. F. (2018). Closed-Loop deep brain stimulation for refractory chronic pain. Frontiers in Computational Neuroscience, 12, 18. https://doi.org/10.3389/fncom.2018.00018

21. Lam, C. M., Latif, U., Sack, A., Govindan, S., Sanderson, M., Vu, D. T., Smith, G., Sayed, D., & Khan, T. (2023). Advances in spinal cord stimulation. Bioengineering, 10(2), 185. https://doi.org/10.3390/bioengineering10020185

22. deCharms, R. C., Maeda, F., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., Gabrieli, J. D. E., & Mackey, S. C. (2005). Control over brain activation and pain learned by using real-time functional MRI. Proceedings of the National Academy of Sciences, 102(51), 18626–18631. https://doi.org/10.1073/pnas.0505210102