TL;DR: Chemotherapy-induced peripheral neuropathy (CIPN) is numbness, tingling, burning, and pain in the hands and feet caused by nerve damage from certain chemotherapy drugs. It develops in up to 68% of patients during treatment and can persist for months or years after chemotherapy ends. There are no Health Canada-approved pharmacological cures. Pre-clinical research on hyperbaric oxygen therapy (HBOT) for CIPN is growing: several laboratory studies show HBOT reduces nerve pain, inflammation, and damage in rodent models of cisplatin- and paclitaxel-induced neuropathy. Human trials are still limited, and CIPN is not currently a Health Canada-recognised indication for HBOT. This Daffodil Month, we explain what CIPN is, what the research shows, and what Canadian cancer survivors need to know.

Estimated reading time: 10 minutes

What Is Chemotherapy-Induced Peripheral Neuropathy?

Chemotherapy-induced peripheral neuropathy (CIPN) is damage to the peripheral nerves caused by cytotoxic chemotherapy. The peripheral nerves are the long, delicate fibres that carry sensory, motor, and autonomic signals between the spinal cord and the rest of the body. When chemotherapy damages these fibres – particularly the long ones that reach the hands and feet – patients experience a characteristic set of symptoms:

Numbness in the fingertips and toes, often spreading up the hands and feet in a “glove and stocking” pattern
Tingling or pins-and-needles sensations (paraesthesia)
Burning pain, electric-shock sensations, or a feeling of walking on pebbles
Allodynia – pain from stimuli that should not be painful, such as light touch, bed sheets, or cold air
Loss of fine motor control – difficulty buttoning shirts, handling coins, or typing
Balance problems and falls from impaired position sense
Cold sensitivity, especially after oxaliplatin

Published reviews estimate that CIPN develops in around 68% of patients within the first month of chemotherapy, falling to roughly 30% at six months as some nerves recover. For a meaningful subset – between 20% and 40% of survivors depending on the drug and regimen – symptoms persist beyond one year and become a chronic survivorship problem. CIPN is one of the most common reasons that chemotherapy doses are reduced or stopped early, which means it is not only a quality-of-life issue but can also directly affect cancer outcomes.

During Daffodil Month, the Canadian Cancer Society highlights survivorship issues that persist long after treatment ends. CIPN is squarely in that category: a chronic, often invisible complication of successful cancer treatment.

Which Chemotherapy Drugs Cause Neuropathy?

Several major classes of cytotoxic drugs are neurotoxic. The risk and pattern of neuropathy differ by drug:

Drug class	Examples	Typical cancer	Neuropathy pattern
Platinum agents	Cisplatin, oxaliplatin, carboplatin	Colorectal, ovarian, testicular, lung, head and neck	Sensory; oxaliplatin causes cold-triggered symptoms
Taxanes	Paclitaxel, docetaxel, nab-paclitaxel	Breast, lung, ovarian, prostate	Sensory, often with burning pain; can persist for years
Vinca alkaloids	Vincristine, vinblastine	Leukaemia, lymphoma, testicular	Mixed sensory and motor; can affect autonomic nerves
Proteasome inhibitors	Bortezomib	Multiple myeloma	Painful sensory neuropathy, often dose-limiting
Immunomodulatory agents	Thalidomide, lenalidomide	Multiple myeloma	Sensory, can be delayed

The probability of developing CIPN increases with cumulative dose, with pre-existing diabetes or peripheral neuropathy, and with combinations of neurotoxic agents. Patients undergoing combination regimens for breast, colorectal, ovarian, or multiple myeloma treatment are particularly likely to experience it.

Why Is CIPN So Difficult to Treat?

Despite decades of research, there is no widely accepted pharmacological cure for CIPN. Guidelines from the American Society of Clinical Oncology continue to identify duloxetine as the only drug with moderate evidence for treating established painful CIPN, and even this offers only modest benefit. No preventive agent has been consistently supported in clinical trials. Canadian oncology practice generally follows these international guidelines.

The difficulty comes from the biology. CIPN is not a single disease; it reflects several overlapping mechanisms:

Mitochondrial dysfunction in long peripheral nerves, which have the highest energy demand
Neuroinflammation driven by activated microglia and inflammatory signalling (including TLR4, NF-kappaB, and related pathways)
Axonal transport disruption from microtubule-targeting drugs like paclitaxel
Apoptosis of dorsal root ganglion neurons, particularly from platinum agents
Ion channel remodelling that produces hyperexcitability and neuropathic pain
Microvascular ischaemia in the nerve itself, which limits recovery

Because CIPN involves energy failure, inflammation, and reduced perfusion of nerves, it has drawn interest from researchers exploring oxygen-based therapies. HBOT affects all three processes – which is why pre-clinical teams have been studying it for CIPN over the past decade.

How Might HBOT Help CIPN?

Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen at pressures typically between 2.0 and 2.4 atmospheres absolute (ATA). This elevated oxygen environment dissolves large amounts of oxygen directly into blood plasma, enabling it to reach tissues with poor perfusion. The biological mechanisms relevant to CIPN include:

Improved oxygen delivery to peripheral nerves with compromised microcirculation
Reduced neuroinflammation – pre-clinical studies show HBOT downregulates TLR4, MyD88, and NF-kappaB inflammatory signalling in damaged nerves
Mitochondrial support by restoring oxygen availability for oxidative phosphorylation
Reduced apoptosis in sensory neurons and supporting cells
Modulation of TRPV1 and TLR4 pathways central to neuropathic pain
Promotion of angiogenesis and recovery of the nerve’s own blood supply (the vasa nervorum)

These mechanisms are not speculative – they have been directly demonstrated in published laboratory studies. The question is whether the pre-clinical benefits translate into meaningful clinical results for cancer patients.

What Does the Research Show?

Research on HBOT for CIPN is currently dominated by pre-clinical (animal) studies, with human clinical trials still very limited. This section summarises what the peer-reviewed evidence base contains as of 2026.

Paclitaxel-Induced Neuropathy – Anti-Inflammatory Mechanism

A mechanistic study on HBOT for paclitaxel-induced peripheral neuropathy demonstrated that HBOT reduced nerve pain and nerve fibre damage in rodents, and showed that the effect was mediated through suppression of the TLR4/MyD88/NF-kappaB inflammatory signalling pathway. This is a central inflammatory cascade in many forms of neuropathic pain and is an attractive therapeutic target.

Simultaneous HBOT During Chemotherapy

A 2023 pre-clinical study explored whether HBOT could be delivered simultaneously with systemic chemotherapy to prevent or reverse CIPN. The investigators reported that concurrent HBOT reversed chemotherapy-induced nerve pain and protected nerve structure, with effects mediated through both TLR4 and TRPV1 inhibition in the central and peripheral nervous systems. Importantly, simultaneous HBOT did not appear to blunt the cancer-treatment effect of the chemotherapy.

Cisplatin-Induced Neuropathy – HBOT Preconditioning

A rat model of cisplatin-induced peripheral neuropathy showed that HBOT delivered before chemotherapy (“preconditioning”) reduced neuroinflammation and protected sensory neurons from apoptosis. This preconditioning approach is an emerging research direction – giving HBOT before or during chemotherapy rather than waiting for neuropathy to develop.

Sex Differences in Response

A study on the effect of HBOT on CIPN in male and female rats found that behavioural and biochemical responses to HBOT differed by sex. This has obvious clinical implications: optimal HBOT protocols for CIPN may differ between men and women, and human trials will need to be powered to detect sex-based differences.

Cannabinoid Signalling and HBOT Analgesia

A further mechanistic study demonstrated that the analgesic effect of HBOT on paclitaxel-induced neuropathic pain involves spinal cannabinoid receptor type 2 (CB2). CB2 is a target of growing interest in chronic pain research, and this finding suggests HBOT and the endocannabinoid system may share overlapping mechanisms.

Summary of the Evidence Base

Pre-clinical (animal) studies: consistent evidence that HBOT reduces neuropathic pain and nerve damage in cisplatin, paclitaxel, and general chemotherapy models, with clear anti-inflammatory and anti-apoptotic mechanisms
Mechanistic plausibility: multiple converging signalling pathways (TLR4, NF-kappaB, TRPV1, CB2) reinforce the biological rationale
Human randomised controlled trials: very limited; CIPN is listed among the conditions with only modest clinical evidence for HBOT to date
Clinical trials in progress: a handful of small trials are recruiting or underway internationally

In short, the biology is promising and the laboratory data are encouraging, but the human clinical evidence is not yet at the level required for routine recommendation.

What Canadian Patients Need to Know

CIPN is not currently one of Health Canada’s 14 recognised conditions for hyperbaric oxygen therapy, and it is not covered by any provincial health plan for this indication. Patients exploring HBOT for CIPN should understand several practical realities:

Coverage: no provincial health plan currently pays for HBOT to treat CIPN. Treatment is self-funded at private hyperbaric clinics or accessed through a clinical trial
Cost: a typical private course is 20 to 40 sessions, with per-session fees in Canada ranging from roughly $150 to $350 depending on the clinic and chamber type
Oncology coordination: any HBOT plan for CIPN should involve the treating oncologist, particularly if the patient is still receiving active chemotherapy or has any history of active malignancy
Conservative care first: continue established CIPN management – duloxetine if prescribed, physiotherapy, acupuncture, footwear and hand-care strategies, fall prevention, and cold-avoidance for oxaliplatin patients
Expectations: the strongest evidence is pre-clinical. Patients should understand that HBOT for CIPN is a research-supported but not regulator-recognised use, and individual response is variable

The Canada Hyperbarics facility directory lists hospital-based and private hyperbaric programmes across the country. Patients should ask any potential clinic about their experience with cancer-survivorship indications, which chemotherapy agents they have treated, the protocol they propose (pressure, session length, course length), and whether they coordinate with the referring oncology team.

Is HBOT Safe for Cancer Survivors?

A common concern among patients and clinicians alike is whether HBOT could promote cancer growth. Multiple safety reviews have concluded that HBOT does not promote tumour growth or recurrence. Because HBOT is a standard treatment for late radiation tissue injury – a complication of cancer therapy – it has accumulated a long safety record specifically in the cancer-survivor population.

The typical side effects of HBOT are mild and usually transient: middle-ear barotrauma (pressure-related ear discomfort), temporary myopia (short-term nearsightedness that resolves after treatment completes), confinement anxiety, and rare episodes of oxygen toxicity. Patients with poorly controlled pneumothorax or specific lung conditions require screening before treatment.

Patients with active malignancy or who are receiving chemotherapy or immunotherapy should always consult their oncologist before considering HBOT. Simultaneous HBOT during chemotherapy is still an emerging research area and should only be undertaken in a coordinated, informed manner.

Frequently Asked Questions

How many HBOT sessions would I need for CIPN?

No consensus protocol exists, because CIPN is not yet a clinically approved indication. Courses used in research range from 20 to 40 daily sessions at 2.0 to 2.4 ATA, similar to standard radiation-injury protocols. A hyperbaric medicine physician should set the specific protocol based on the patient’s chemotherapy history and neuropathy severity.

Can HBOT prevent CIPN if I start it before chemotherapy?

Preconditioning – starting HBOT before chemotherapy – has shown promising results in animal models. In humans, this strategy is still experimental and is not a standard Canadian practice. Patients interested in this approach should ask about clinical trials rather than self-funding an unproven preventive course.

Can HBOT be delivered at the same time as chemotherapy?

Simultaneous HBOT during chemotherapy has been investigated in pre-clinical work, with initial evidence suggesting it did not reduce the anticancer effect of the chemotherapy. This concept has not yet been established in human trials and should not be pursued without direct oncologist oversight.

Will OHIP, MSP, or another provincial plan cover this?

Not for CIPN specifically. Provincial plans cover HBOT only for Health Canada’s 14 recognised conditions – CIPN is not on that list. Coverage may apply if a patient has a co-existing recognised indication (for example, a non-healing diabetic wound or radiation injury) but not for CIPN in isolation. Confirm with the treating facility before assuming coverage.

Should I stop duloxetine if I start HBOT?

No. HBOT is being studied as an adjunct, not a replacement, for established CIPN care. Any medication change should be discussed with the prescribing oncologist or family physician.

Key Takeaway

Chemotherapy-induced peripheral neuropathy is a common, under-treated survivorship problem with limited pharmacological options. Pre-clinical research on hyperbaric oxygen therapy shows that HBOT reduces neuropathic pain and nerve damage in rodent models of cisplatin- and paclitaxel-induced neuropathy, acting through well-mapped inflammatory and apoptotic pathways. Human clinical evidence is still limited and CIPN is not a Health Canada-recognised indication. Patients who pursue HBOT for CIPN in Canada will generally self-fund treatment at a private clinic and should do so only as part of a coordinated plan with their oncology team and an experienced hyperbaric medicine physician.

References

This content is for informational purposes only and does not constitute medical advice. HBOT for chemotherapy-induced peripheral neuropathy is an investigational use and is not currently listed under Health Canada’s recognised conditions for hyperbaric oxygen therapy. Patients should consult their oncologist and a certified hyperbaric medicine specialist before pursuing any HBOT-based treatment plan. Canada Hyperbarics is an independent educational resource and is not affiliated with any specific clinic or manufacturer.

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Chemotherapy-Induced Peripheral Neuropathy and HBOT: What the Research Shows