Neuropathy, CIPN And Pain
Pain is a complex system involving sensory cells, conducting nerves and multiple brain networks. Pain conditions such as neuropathy occur when this system is damaged or malfunctioning. At Neuromod Labs, we focus on non-invasive therapies rooted in Dr Prinsloo's research to ease the burden of these conditions.
Chemotherapy Induced Peripheral Neuropathy (CIPN)
Chemotherapy‑Induced Peripheral Neuropathy (CIPN) happens when certain cancer treatments irritate or damage the nerves that help you feel touch, temperature, and pain. When those nerves aren’t working well, people may notice tingling, numbness, burning, or discomfort in their hands and feet. CIPN affects both the nerves themselves and the way the brain interprets those signals. There are several ways to ease CIPN symptoms, but only a few have strong scientific support:
● Non‑invasive neuromodulation: Gentle external stimulation or brain‑training exercises that help the nervous system handle sensory signals more comfortably thereby easing the perception of pain.
● Medications: Can reduce nerve‑related pain by adjusting how nerves send signals.
● Invasive neuromodulation: An implanted device that interrupts pain signals; involves a minor procedure.
Our work has always focused on carefully measuring how each intervention affects the nervous system, and we know that every person’s experience is unique. That’s why we develop personalized, multifactorial plans tailored to your specific needs. If you’d like to explore what approach may best support your needs, book a free 15‑minute consultation.
Other Pain Conditions
Our approach is not limited to chemotherapy‑induced neuropathy. The same principles: precise measurement, nervous‑system‑focused methods, and personalized, multifactorial planning, can also support a range of other chronic pain and sensory conditions. Common areas we work with include:
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Diabetic or metabolic neuropathy
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Post‑surgical or post‑radiation nerve pain
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Complex Regional Pain Syndrome (CRPS)
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Persistent nerve pain after injury
Across these conditions, the nervous system plays a central role in how pain signals are generated and interpreted. By understanding how your sensory pathways and brain networks are functioning, we can identify strategies that help reduce discomfort and support daily functioning.
What Is Pain? The Longer Story
Pain is a complex experience that serves as the body's alarm system for tissue damage. It makes us stop to take care of ourselves and has significant survival value.
Rather than being a simple "direct line" from an injury to the conscious mind, pain involves a sophisticated network. This system spans specialized sensory receptors, different conducting nerve fibers, and multiple regions of the brain that dictate how the pain physically feels and emotionally affects you. It can be broken down into five main parts:
1. Peripheral Detection: The Sensory Neurons
The process begins with different kinds of specialized sensory neurons that detect harmful stimuli.
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Mechanical - physical pressure, cutting, or crushing.
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Thermal - temperatures below 59F and above 113F
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Chemical -internal tissue damage or external irritants.
2. Signal Transmission: The Conductive Nerves
Sensory neurons create an electrical signal that travels to the spinal cord along different nerve fibers. Fast fibers send a sharp signal telling the brain where and what the injury is (e.g., stepping on a nail). Slow fibers send dull, aching, burning signal that lingers after the initial injury to enforce rest and protective behaviors.
3. Central Processing: The Spinal Gate
At the spinal cord signals are processed before they even reach the brain, passing through a "gate". The spinal cord can act as a filter, dampening or amplifying the pain signals based on competing inputs (such as rubbing a stubbed toe, which sends competing, non-painful signals through faster touch fibers to "close" the gate).
4. Complex Interpretation: The Brain & Emotional Experience
If the signal passes the spinal gate, it ascends to the brain. The brain does not possess a single "pain center." Instead, it processes the incoming signal through large networks that split the experience into two components.
The Sensory-Discriminative Network of the thalamus and the somatosensory cortices determine the physical location, intensity, and duration of the pain.
The Affective-Motivational Network (The Emotional Experience) processes the unpleasantness and the suffering of pain to create an emotional response for survival and learning about threats. Several brain areas are involved in this network.
5. Top-Down Control: The Descending Modulatory Pathway
In addition to the four main steps, the brain is not just a passive receiver; it can actively turn the volume of pain up or down by sending signals back down the spinal cord.
If Pain Is Useful, What Is Neuropathy?
When the nervous system experiences intense, prolonged injury, or disease (such as diabetes, viral infection, or physical trauma), the structural "wiring" of the pain system changes through a process called maladaptive neuroplasticity. [1]. Instead of reporting external damage, the alarm system itself breaks and begins misfiring. The transition can happen across the four major elements of the pain system.
1. Peripheral Sensory Neurons
Under normal conditions, peripheral nociceptors only fire when triggered by an actual threat. However, nerve damage or persistent inflammation can cause the sensory neurons to send no signal leading to numbness. Alternatively the neurons can become hyper-excitable and send signals without any physical trigger. Called 'ectopic firing', the brain receives random pain signals, which can feel like spontaneous shooting, burning, or electric shocks.
2. Conducting Nerves: Cross-Talk and Structural Damage
Damaged nerve fibers can lose their protective insulation (demyelination). When bare nerve fibers lie next to each other, electrical signals can jump from one fiber to another. This cross-talk can cause a normal stimulus to activate a pain nerve, causing light touch to feel agonizing.
3. The Spinal Cord Gate: Sensitization & Rewiring
Continuous bombardment of pain signals causes inhibitory neurons (the "gatekeepers" that normally suppress pain) lose their dampening power. Non-painful touch fibers can also make new connections into the pain-processing layers of the spinal cord. This structural rewiring creates two hallmark clinical signs of neuropathy:
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Allodynia: Light, normally pleasant stimuli (like clothes rubbing against the skin) are severely painful because the touch fibers are now directly wired into the spinal pain gate.
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Hyperalgesia: Mildly painful stimuli result in an exaggerated, agonizing pain response because the spinal amplification system is stuck on "high volume".
4. Brain Networks: Cortical Reorganization & Glial Activation
The changes finally reshape the brain's processing, embedding the neuropathic pain into its network state. Over time, the somatosensory cortex reorganizes and the brain's descending modulatory pathway (the top-down volume control) fails. The emotional networks (amygdala and anterior cingulate cortex) become locked in a perpetual loop of distress, anxiety, and survival-driven stress, which worsens the neuropathy.
How Is Neuropathy Treated?
Treating neuropathy requires a multi-layered approach to target nerve pain, alter pain signaling pathways, and retrain how the brain processes these sensations. Management typically advances from systemic oral medications to targeted electrical interventions and cutting-edge brain-computer therapy. [2]
Drug Therapies
First-line pharmacological treatments suppress nerve signals to provide systemic pain relief. [3]
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Gabapentinoids: Medications like gabapentin and pregabalin are the most common first-line choices. They calm hyper-excited neurons by binding to voltage-gated calcium channels to slow down pain transmission.
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Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Drugs such as duloxetine and venlafaxine elevate neurotransmitter levels in the spinal cord. This boosts the body's natural descending pathways that inhibit pain. Notably, they are the primary medications recommended by oncology guidelines for chemotherapy-induced peripheral neuropathy (CIPN).
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Tricyclic Antidepressants (TCAs): Older medications like amitriptyline and nortriptyline block the reuptake of serotonin and norepinephrine while mildly blocking sodium channels to interrupt pain.
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Topical Agents: For localized neuropathy (such as in the feet), prescription 5% lidocaine patches or 8% capsaicin creams can be applied directly to the skin to desensitize local pain receptors.
Invasive Neuromodulation
When oral medications fail to provide sufficient relief, invasive neuromodulation can be used to block pain signals surgically before they reach the brain. These outpatient procedures are targeted and reversible. [3]
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Spinal Cord Stimulation (SCS): Electrodes are surgically positioned near the spinal cord and wired to a small battery implanted under the skin. Low-level electrical currents intercept and replace sharp nerve pain with a gentle tingling sensation (or no sensation at all).
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Dorsal Root Ganglion (DRG) Stimulation: This specialized form of SCS targets the specific cluster of nerve cells (the ganglion) responsible for transmitting sensory information from the limbs.
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Peripheral Nerve Stimulation (PNS): Small electrodes are placed alongside the specific peripheral nerve causing the issues (rather than the spine) to alter local pain pathways.
Non-Invasive Neuromodulation and Dr Prinsloo's Research
Non-invasive techniques alter nervous system activity without surgical incisions or systemic drugs. While traditional devices like Transcutaneous Electrical Nerve Stimulation (TENS) and Scrambler Therapy use external pads to change peripheral nerve messaging, groundbreaking research focuses directly on the central nervous system. [4, 5, 6]
Dr. Sarah Prinsloo at The University of Texas MD Anderson Cancer Center has pioneered the use of EEG-based neurofeedback to treat chemotherapy-induced peripheral neuropathy (CIPN). Chemotherapy often damages peripheral nerves, but the severity of chronic pain, tingling, and numbness is dictated by how the brain interprets those aberrant signals. Dr. Prinsloo identified the precise brain signatures that process both the physical and emotional aspects of neuropathic pain.
Clinical trials published in journals like Cancer have proven that this protocol induces neuroplasticity, teaching the brain to reinterpret or ignore the chaotic pain signals coming from the limbs. Studies showed that neurofeedback significantly and safely reduced pain intensity, numbness, and fatigue. These benefits persisted for months after the 20-session therapy concluded, providing a lasting, non-addictive option for cancer survivors.
References
[1] Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 2009; 32: 1–32. - PMC - PubMed
[2] Kaye AD, Armistead G, Amedio LS, Manthei ME, Ahmadzadeh S, Bernhardt B, Shekoohi S. Evolving Treatment Strategies for Neuropathic Pain: A Narrative Review. Medicina (Kaunas). 2025 Jun 10;61(6):1063. doi: 10.3390/medicina61061063. PMID: 40572751; PMCID: PMC12195047.
[3] Shinu P, Morsy MA, Nair AB, Mouslem AKA, Venugopala KN, Goyal M, Bansal M, Jacob S, Deb PK. Novel Therapies for the Treatment of Neuropathic Pain: Potential and Pitfalls. J Clin Med. 2022 May 26;11(11):3002. doi: 10.3390/jcm11113002. PMID: 35683390; PMCID: PMC9181614.
[4] Prinsloo S, Kaptchuk TJ, De Ridder D, Lyle R, Bruera E, Novy D, Barcenas CH, Cohen LG. Brain-computer interface relieves chronic chemotherapy-induced peripheral neuropathy: A randomized, double-blind, placebo-controlled trial. Cancer. 2024 Jan;130(2):300-311. doi: 10.1002/cncr.35027. Epub 2023 Sep 21. PMID: 37733286. https://pubmed.ncbi.nlm.nih.gov/37733286/
[5] Prinsloo S, Novy D, Driver L, Lyle R, Ramondetta L, Eng C, Lopez G, Li Y, Cohen L. The Long-Term Impact of Neurofeedback on Symptom Burden and Interference in Patients With Chronic Chemotherapy-Induced Neuropathy: Analysis of a Randomized Controlled Trial. J Pain Symptom Manage. 2018 May;55(5):1276-1285. doi: 10.1016/j.jpainsymman.2018.01.010. Epub 2018 Feb 5. PMID: 29421164. https://pubmed.ncbi.nlm.nih.gov/29421164/
[6] Prinsloo S, Gabel S, Lyle R, Cohen L. Neuromodulation of cancer pain. Integr Cancer Ther. 2014 Jan;13(1):30-7. doi: 10.1177/1534735413477193. Epub 2013 Feb 25. PMID: 23439659. https://pubmed.ncbi.nlm.nih.gov/23439659/
Content reviewed by: Dr Sarah Prinsloo, PhD
Last Updated: June 2026