Neuropathic pain: why common painkillers aren't enough

What neuropathic pain is and what it feels like

Neuropathic pain is pain that arises from an injury or dysfunction of the nervous system, either peripheral (the nerves) or central (the spinal cord or brain). It is not pain from inflammation or tissue damage: it is pain coming from the nerves themselves, which are transmitting abnormal signals.

The way it presents is typical and usually points toward the diagnosis. Patients describe sensations such as:

• Persistent burning in a specific area
• Electric shocks that appear spontaneously or with movement
• Pins and needles or a stabbing, needle-like sensation
• Tingling or numbness that hurts
• Allodynia: pain from stimuli that shouldn't hurt (clothing brushing the skin, a light touch, the wind)
• Hyperalgesia: a mildly painful stimulus triggers pain that is out of proportion

When a patient describes their symptoms in these terms, there is almost always a neuropathic component. And that component requires a treatment different from that of ordinary nociceptive pain.

One technical nuance I always insist on explaining: neuropathic pain does not respond well to the usual painkillers. Anti-inflammatories and common analgesics tend to offer poor relief, and that often leads patients to conclude that 'nothing can be done'. The reality is different: there are medications specific to this type of pain — certain anticonvulsants and antidepressants at doses and schedules designed for neuropathy — that can completely change the picture. The problem is not that there is no treatment; it's that the correct diagnosis often comes too late.

Most common causes

Radiculopathies

Irritation or compression of a nerve root as it exits the spine produces pain that radiates along the nerve's path: sciatica (L5 or S1 root), cervical radiculopathy (cervical roots running into the arm). This is probably the most common cause of neuropathic pain in clinical practice.

Postherpetic neuralgia

After an episode of herpes zoster (shingles), some patients develop persistent neuropathic pain in the affected area, especially older adults. It is one of the hardest neuropathic pains to treat, which is why it is worth preventing by treating the acute zoster episode well.

Painful diabetic neuropathy

Patients with long-standing diabetes can develop neuropathic pain in the feet (typically symmetrical, in a "stocking" distribution) due to peripheral nerve damage. Good glycemic control prevents progression, but once the pain has set in, it requires specific treatment.

Trigeminal neuralgia

Very intense, brief electric shocks in the face, triggered by touching trigger points on the face or by chewing. It has very specific and effective treatments.

Chronic post-surgical pain

Some surgeries (thoracotomy, mastectomy, hernia repair, amputation) leave behind chronic neuropathic pain from nerve injury during the procedure. It is partly preventable with good perioperative management.

Other causes

Carpal tunnel syndrome, meralgia paresthetica, pudendal neuralgia, intercostal neuralgia, phantom limb pain after amputation, and chemotherapy-induced neuropathies, among others.

Why it doesn't respond to anti-inflammatories

Nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, naproxen) act on the mediators of tissue inflammation. They are effective when the pain is inflammatory: a sprain, acute arthritis, a recent muscle strain.

Neuropathic pain does not have that inflammatory basis. The nerve is firing signals because of a functional or structural alteration, not because of local inflammation. That is why NSAIDs are of little or no benefit, and patients who keep escalating the dose only end up with side effects: gastritis, kidney impairment, high blood pressure.

The same goes for common opioids (tramadol, codeine): they may provide some initial relief, but their efficacy in pure neuropathic pain is limited, and the risks of long-term use (tolerance, dependence, opioid-induced hyperalgesia) are high.

The medications that do work for neuropathic pain are those that act on the mechanisms of the sensitized nerve: gabapentinoids, SNRI antidepressants, certain antiepileptics. These are medications prescribed all the time in Pain Medicine with very good results, even though many patients have never heard of them.

Specific medication treatment

The pillars of medication treatment for neuropathic pain are four groups of drugs. The choice depends on the type of pain, the patient's other health conditions and the side-effect profile — and it is often necessary to combine two at low doses to achieve the best balance between efficacy and tolerability.

• Gabapentinoids (gabapentin, pregabalin): first-line agents. They act on calcium channels, modulating the release of excitatory neurotransmitters. Useful in radiculopathies, diabetic neuropathy, postherpetic neuralgia and fibromyalgia.
• SNRI antidepressants (duloxetine, venlafaxine): they inhibit the reuptake of serotonin and norepinephrine, key neurotransmitters in the descending pathways that modulate pain. Very useful in diabetic neuropathy and widespread chronic pain.
• Low-dose tricyclic antidepressants (amitriptyline, nortriptyline): they act on multiple systems involved in neuropathic pain. Low doses are well tolerated and do not produce the typical antidepressant effect.
• Topical 5% lidocaine patches: for localized postherpetic neuralgia and other focal neuropathic pains. Excellent safety profile because almost none of it is absorbed.

The general rule: start low, increase gradually as tolerated, allow at least 4 weeks at a stable dose before judging efficacy, and combine two medications with different mechanisms rather than pushing a single one to high doses.

My approach to neuropathic pain combines first-line medications, adjusted patiently until the effective dose is found, with procedures when there is a clear target: selective nerve blocks, pulsed radiofrequency or, in selected cases, neuromodulation. I also always look at the underlying cause: diabetic neuropathy, nerve entrapments, postherpetic neuralgia, post-surgical sequelae, nerve root injuries. Treating the symptom without understanding the context usually gives partial results. The plan is built for each patient — it isn't copied from a protocol.

When to add interventional treatment

Many neuropathic pains respond to well-conducted medication treatment. But in other cases, adding image-guided interventional procedures changes the outcome:

• Selective nerve root blocks: for radiculopathies — both diagnostic and therapeutic.
• Epidural injections: lumbar or cervical, for herniated discs with radicular pain.
• Sympathetic blocks: for certain neuropathic pains with a sympathetic component (stellate ganglion for the upper limb, lumbar sympathetic block for the lower limb).
• Pulsed radiofrequency: a neuromodulation technique that can help in some neuropathic conditions where conventional radiofrequency ablation cannot be used because of the risk of nerve damage.
• Targeted blocks: of the greater occipital nerve for occipital headache, of the pudendal nerve for pudendal neuralgia, intercostal blocks, and others.
• Neuromodulation: for selected cases refractory to conventional treatment (spinal cord stimulators, dorsal root ganglion blocks).

The practical rule: well-conducted medication treatment is the foundation. Procedures are a powerful tool, but they don't replace comprehensive medical management. Combining them correctly is what delivers the best results.

What defines a good outcome in neuropathic pain is not always the complete disappearance of the symptom, but reaching an intensity and frequency compatible with a normal life: sleeping through the night, working, exercising, not thinking about the pain all day. When a patient comes back and tells me they no longer think about their pain every hour, I know the treatment is working. Pain medicine has a great deal to offer in these conditions, as long as they are identified early and managed with a serious, stepwise and sustained plan.

Dr. Mauricio Casarsa

Anesthesiologist, specialist in Pain Medicine and Interventional Pain Management. Postgraduate training at UBA (Fundación Dolor) and UNLP (CAIDBA). Staff physician at Hospital Alemán in Buenos Aires.

MN 137756 · San Isidro · Villa Urquiza