Treating Neuropathic Pain: A Practical Algorithm for Clinicians

If there’s one thing that stands out about neuropathic pain, it’s that it can make life pretty miserable—for both patients and providers. The trick with this beast is to recognize it early, be systematic, and recognize there’s no magic bullet. What we do have: a logical algorithm, and some pragmatic clinical pearls to help treat it more effectively.

Step One: Nail the Diagnosis

Start by asking the right questions. Neuropathic pain presents as burning, pins and needles, numbness, itching, crawling, painful cold, squeezing, and that deep ache. Check for distribution—it’ll follow nerve roots or peripheral nerves, or show up glove-and-stocking style in peripheral neuropathy. If the sympathetic system is involved, expect swelling, strange color changes, temperature swings, and sweating.

You can save yourself some headaches by using decent questionnaires. DN4, LANSS, and PainDetect all have good sensitivity. Get patients to fill this out in the waiting room and you’ve already got a head start.

And don’t skip the pain diagram. Get the patient to draw their pain, use keys—lightning bolts for electric pain, circles for numbness, dots for pins and needles. This gets invisible pain mapped onto the page, streamlines your thinking, and helps with clear communication. Patients explain things in all sorts of ways; standardize the approach or you’ll get lost in the weeds.

Step Two: Address the Amplifiers

Neuropathic pain rarely arrives alone, let alone when a patient has been struggling with it for a long time. Look for mood swings, depression, anxiety, insomnia, and fatigue. These aren’t just “side issues”—they amplify pain and can wreck quality of life faster than most meds. Suss these out early and deal with them in parallel with pain management—not as an afterthought.

Remember, amplifiers like anxiety upregulate pain but are not the lone cause—don’t let patients feel blamed; just treat the full picture. If sleep is a problem, refer to a sleep specialist or get their sleep issues sorted—no need to reach straight for the sedatives every time.

Step Three: Medications—Realities and Trade-offs

Start simple. If no one’s started them on amitriptyline, well, that’s your go-to TCA. The number needed to treat (NNT) is 3.4, so you’re looking at 25% of patients for whom it actually works—don’t be surprised when it doesn’t land. Duloxetine is next, NNT about 6. Gabapentin and pregabalin finish the big three—NNT is 8, so only about 11% of folks respond at that 30-50% pain reduction mark.

Four- to six-week trials on all these. If effective, stick with it; if not—or if side effects outweigh the benefit—bin it and move to the next. Don’t let patients feel guilty if meds don’t work: it’s not their fault, that’s just how the dice roll. It working actually makes you the outlier.

Here’s the nuance: If the patient can’t sleep, go with amitriptyline since it affects that as well. If they’re struggling with untreated depression, duloxetine is up as it attacks both issues. Already on antidepressants? Gabapentin’s easier to taper than Lyrica, so usually start there.

Prepare for side effects. With pregabalin: weight gain and brain fog are the big ones. For high-functioning professionals, brain fog can be brutally disabling. Adjust plans accordingly and always reevaluate as other things change—no one’s wedded to one drug forever.

Step Four: Combinations and What Works in Reality

Half your patients with diabetic neuropathy will need more than one medication. Combo therapy can bump the pain relief, but side effects add up just as fast. Sometimes adding gabapentin to amitriptyline lets you lower the dose and net better function with fewer side effects. Work the combinations logically and don’t expect perfection—40-50% pain relief might be the ceiling.

Second-line therapies (tramadol, for example) are rarely first up for Dan. Nausea, falls, and cognitive hit are high for older patients, plus it dances with serotonin and risks serotonin syndrome if you’re not careful—brisk reflexes and anxiety are early flags on that front.

Step Five: Topical Solutions

Localized pain can often be tackled with topical agents. Amitriptyline, gabapentin, ketamine, or clonidine—trial these. Low risk except for skin reactions and cost (usually not covered by insurance or PBS). Capsaicin, now FDA-approved for diabetic neuropathy, also worth considering to cut down peripheral sensitization.

Don’t expect miracles, and be upfront: some patients find these useless, others get their life back.

Step Six: When to Refer—Specialist Input and Interventions

If you’ve worked through the above and the patient is still struggling, time for a specialist referral. Expect the rotation through less mainstream anticonvulsants and maybe ketamine. Dan doesn’t do pumps or hardcore meds like tapiramate or lamotrigine—refer out and ask colleagues if it’s worth it. The NNT and side effects often keeps rising as you move through these options.

Interventions have their place. Pulsed radiofrequency seems promising, especially post-epi for nerve roots, but data’s still emerging. Adhesiolysis helps with scarring, especially post-surgery. Sympathetic blocks for those with color, swelling, and sweating issues. Avoid burning nerves with thermal RF unless you like cleaning up disasters.

Neuromodulation—Last Lines and Real-World Expectations

Once everything else fails and pain is unrelenting, or depending on patient preferences, neuromodulation (spinal cord stimulation or DRG stims) comes in. You trial leads and look for meaningful functional improvements—not just in pain but mood, sleep, sociability etc. I look for at least 80% pain relief in trial periods (guidelines say 50%, but in practice, less doesn’t really justify the downsides/risks).

Remember: these aren’t forever—patients can explant if things settle or side effects get out of hand. Complication rates hover around 3-4%; most are lead migration or pocket pain. Don’t get sucked in by high complication claims—always know your denominators. Subcutaneous 5% glucose is my current favorite for pocket pain (try before explanting).

Opioids: Caution and Calculation

Opioids will knock off neuropathic pain, but only briefly—NNT is 2.1 for mixed cases, 5.1 for peripheral. Number needed to harm? About 17. The problem is they make pain worse long term (opioid-induced hyperalgesia) and steal motivation, clarity, and agency. Short-term, understandable in certain situations; long-term, beware. Guidelines say stay under 90 milliequivalent of morphine—easy enough to calculate. But for most, I’d prefer to leave opioids out of the mix altogether if possible.

Targeted Drug Therapy: Rarity, Not Routine

Intrathecal pumps are for a small, specialized subset. Microdose opioids or ziconidide can be effective but come with complications—refer to a pump specialist; it’s outside most physicians usual arena.

Our Takeaway for You:

Ask, diagram, use questionnaires, and look for amplifiers and consequences. Tackle meds stepwise, trial topicals if local, combine when needed, and refer out when options are exhausted. Intervene judiciously, weigh neuromodulation carefully, and keep opioids as a reluctant last resort.

Getting neuropathic pain under control can be tricky, but there’s a structure—and if you work through it and listen to your patients, you'll help more than you frustrate. And if you’re in doubt, laminate the algorithm and keep it somewhere handy.

For more insight and practical advice, tune in to episode 17 of It’s Not in Your Head Podcast.