Nerve Pain · Ketamine Therapy · Reviewed by Samuel Caruthers, MD
It usually starts in the toes and it usually gets worse after dark. Burning, tingling, a feeling like walking on gravel, or a strange numbness that somehow still hurts. During the day you can distract yourself. At night, with nothing else competing for your attention, it takes over. Patients often tell us the same thing: it is not the daytime pain that breaks them down, it is the third consecutive night without sleep.
If that describes your experience, you already know what diabetic peripheral neuropathy feels like. What is less widely understood is why it becomes so difficult to treat over time, and why some patients who have exhausted the standard medications are now being evaluated for ketamine infusion therapy.
What is happening in the nerves, and then in the spinal cord
Diabetic peripheral neuropathy begins as nerve damage. Sustained high blood glucose injures the small blood vessels that supply peripheral nerves, and the longest nerves in the body, the ones running to the feet, are affected first. That is why symptoms typically appear in a stocking distribution and move upward over years rather than appearing everywhere at once.
That much is familiar. The part that matters for treatment is what happens next.
When damaged nerves send abnormal signals continuously over months and years, the spinal cord and brain adapt to that input. The pathways carrying the signal become more responsive, a process closely related to the central sensitization seen in other chronic pain conditions. At that point you are no longer dealing only with damaged nerves in the feet. You are also dealing with a nervous system that has learned to amplify what those nerves are sending.
This is why excellent blood sugar control, which is essential and which slows further damage, often does not resolve pain that is already established.
It is also why patients sometimes feel dismissed. They are told to manage their diabetes better, they do exactly that, and the burning does not stop. Both things can be true: the glucose control is working and the pain persists, because the pain has become partly a separate problem.
Why it gets worse after dark
The nighttime pattern is so consistent that patients often assume it must be psychological. It is not, and there are several straightforward reasons for it.
There is less competing input. During the day your nervous system is processing movement, pressure, temperature, sound, and everything else you are doing. That input competes with pain signals for attention. Lying still in a dark, quiet room removes the competition, and the pain signal is left as the loudest thing in the system.
Skin temperature changes. Peripheral blood vessels dilate in the evening as part of the normal process that precedes sleep, and warming of the feet can intensify burning sensations in damaged small nerve fibers.
Pain perception varies over the day. There is a circadian rhythm to pain sensitivity, and for many people it runs against them at night.
The loop reinforces itself. Poor sleep lowers pain thresholds, and lowered thresholds make the next night worse. Once that cycle establishes, it continues without any change in the underlying nerve damage.
Why this matters when you describe your symptoms
Patients often report their pain based on how they feel in a clinic at two in the afternoon, which is frequently their best hour. If your nights are far worse than your days, say so explicitly. It changes the picture, and it is part of what a physician needs to know to judge whether a treatment is working.
Where first-line treatment stops being enough
Standard treatment usually begins with medications such as gabapentin or pregabalin, duloxetine, or in some cases a tricyclic antidepressant like amitriptyline. Topical agents are sometimes added. These are appropriate, evidence-supported first choices and they should be tried properly before anything else is considered.
They also have well-known limits. In neuropathic pain generally, these medications tend to produce partial relief in a subset of patients rather than full relief in most, and the side effects that come with them, sedation, dizziness, weight gain, cognitive dulling, cause a meaningful number of people to stop taking them or to stay at a dose lower than would be effective.
So the common pattern looks like this. A patient tries gabapentin, gets some benefit and considerable grogginess. They switch to duloxetine, get some benefit and some nausea. They add a topical. Each step helps a little. The sum is still a person who cannot sleep through the night.
The question worth asking your physician
Not “is there a stronger medication,” but “is there something that works on a different mechanism.” Escalating within the same category of treatment tends to produce more side effects rather than more relief. Changing the target is a different conversation.
How ketamine approaches the problem differently
At the low doses used in pain infusions, ketamine acts mainly as an NMDA receptor antagonist. NMDA receptors sit at the center of the amplification process described above, contributing to the wind-up phenomenon in which repeated pain signaling makes the nervous system progressively more responsive.
In neuropathic pain, that amplification is a substantial part of what patients are actually experiencing. Targeting it directly is a different strategy from the anticonvulsants and antidepressants used first line, which modulate signaling in other ways.
Neuropathic pain conditions are, broadly speaking, where the evidence for ketamine in chronic pain is strongest, though strongest is a relative term and the picture is far from settled. Studies have generally been small, protocols have varied widely, and the duration of benefit reported has been inconsistent. Some patients experience relief lasting weeks; others considerably less. What is reasonably well supported is that a meaningful proportion of patients with neuropathic pain do experience short-term reduction in pain intensity.
Two things we want to be clear about
Ketamine does not repair damaged nerves. It does not treat diabetes, and it is not a substitute for glucose control, which remains the single most important thing you can do to protect the nerves you still have. What it may do, for some patients, is reduce the pain that damaged nerves are producing.
Who tends to be considered
Evaluation for ketamine infusion in diabetic neuropathy generally makes sense for patients who have a clear diagnosis, who have given appropriate first-line medications a fair trial at adequate doses, and whose pain continues to interfere with sleep and daily function.
Because this population tends to be older and to carry other medical conditions, the screening step matters more here than in some other indications. Cardiovascular status in particular needs review, since ketamine can transiently raise blood pressure and heart rate. Poorly controlled hypertension, significant cardiac disease, and certain other conditions may make treatment inadvisable.
There is also a practical requirement worth planning around. You cannot drive after an infusion, and a course of treatment means arranging a ride each time. Patients who sort this out before starting are considerably more likely to finish.
What a course of treatment looks like
Infusions take place in the office with continuous monitoring. Pain protocols run longer than the short infusions used for mood conditions, and there is a recovery period before you leave.
Treatment usually begins with a series over a compressed period rather than a single visit, because a one-time infusion rarely produces durable change in a condition that has been building for years. If the initial series helps, maintenance infusions at longer intervals may follow. The number and spacing is decided based on your response, not fixed in advance.
| Option | Mechanism | Practical notes |
|---|---|---|
| Glucose control | Slows ongoing nerve damage | Essential and non-negotiable, but often does not relieve established pain |
| Gabapentin / pregabalin | Calcium channel modulation in nerve signaling | First line, daily dosing, sedation and dizziness are common limiters |
| Duloxetine / amitriptyline | Descending pain inhibition via neurotransmitters | First line, daily dosing, side effects lead some patients to stop |
| Ketamine infusion | NMDA receptor activity linked to central amplification | Off-label, self-pay, in office, requires a driver, typically a series |
What else belongs in the plan
Ketamine, if it is appropriate for you, is one component rather than a standalone answer. A sound plan for painful diabetic neuropathy usually runs on several tracks at once.
Glucose management stays central. It is the only thing on this list that slows further nerve damage. Nothing described in this article replaces the work you and your diabetes team are doing, and improvements there protect the function you still have.
Foot protection matters more than people expect. Reduced sensation means injuries go unnoticed. Daily inspection and appropriate footwear prevent problems that are far harder to treat than the pain itself.
Sleep is worth treating directly. Because the pain and sleep loop runs in both directions, addressing sleep can lower pain independently of anything aimed at the nerves.
Movement, within limits. Gentle regular activity supports circulation and appears to benefit neuropathic symptoms over time, though it needs to be matched to your balance and sensation.
We are glad to coordinate with your endocrinologist or primary care physician rather than working in isolation. Pain treatment that ignores the rest of the picture tends to underperform.
Cost, access, and location
North Jersey Interventional Pain Center is out of network, and ketamine infusion for chronic pain is generally not covered by insurance. You will get specific figures at your consultation so you can weigh the cost of a full series before you commit to the first infusion rather than partway through.
Our Parsippany office sees patients from across Morris County, including Lake Hiawatha and Rockaway, with additional locations in Clifton, Hackettstown, and Hamburg.
Frequently asked questions
Will ketamine reverse my neuropathy?
No. Nerve damage from diabetes is not reversed by ketamine. The goal is reduction in pain, not repair of the nerves. Protecting the nerves you have still depends on glucose control and the care of your diabetes team.
Can I stay on gabapentin or duloxetine?
Often yes, and many patients do. Your full medication list needs review before treatment because some combinations require adjustment, but any change is made with your prescribing physician, not unilaterally.
Is this covered by insurance?
Generally no. This practice is out of network and does not participate with Medicare or Medicaid. You will receive clear pricing at your consultation.
How soon would I know whether it helps?
Some patients notice change within the first few infusions, others not until further into a series, and some do not respond at all. Your physician will discuss a reasonable point at which to assess whether continuing makes sense.
I have heart problems. Can I still be evaluated?
You can be evaluated, and that is exactly why the evaluation exists. Ketamine can transiently raise blood pressure and heart rate, so cardiac history is reviewed carefully. Some patients are not appropriate candidates, and we will tell you directly if that is the case.
Do I need a referral from my endocrinologist?
No referral is required. Bringing recent records is helpful, and we are glad to communicate with the physicians managing your diabetes.
Still awake at 3 a.m. because of your feet?
A consultation will tell you whether ketamine infusion is a reasonable option in your case. If it is not, we will say so and talk through what else might be.
Medical disclaimer. This article is for general educational purposes and is not medical advice, nor does it create a physician-patient relationship. Ketamine infusion therapy for diabetic peripheral neuropathy is an off-label use and is not FDA approved for this indication. Individual results vary and no outcome is guaranteed. Ketamine does not treat diabetes and is not a substitute for glucose management. Do not start, stop, or change any medication based on this article. Discuss your circumstances with a qualified physician who has reviewed your full medical history. If you are experiencing a medical emergency, call 911.