Nerve or neuropathic pain has long been a tricky condition to treat effectively. However, a new study has comprehensively evaluated current drug and non-drug therapies to provide up-to-date guidelines to inform treatment options for those with the condition.
It’s estimated that nerve, or neuropathic, pain affects between 6.9% and 10% of the global population. Often described as burning, electrical, or shooting, this type of pain is usually accompanied by abnormal sensations like tingling, numbness, or “pins and needles.” Neuropathic pain can significantly impact quality of life.
A new study by the International Association for the Study of Pain’s (IASP) Neuropathic Pain Special Interest Group (NeuPSIG) has comprehensively examined the effectiveness of current drug and non-drug therapies for neuropathic pain to compile up-to-date treatment guidelines.
“There is an unmet need for effective and safe treatments for neuropathic pain,” said study co-author Michael Ferraro, a doctoral researcher at the Center for Pain IMPACT, Neuroscience Research Australia (NeuRA), and the School of Health Sciences at the University of New South Wales (UNSW). “Our research looked at the evidence for all drugs and nerve stimulation treatments, considering effectiveness, safety, cost, accessibility, and patient perspectives.”
Although there are many causes of neuropathic pain, it’s commonly associated with specific conditions, including diabetes (peripheral neuropathy), chemotherapy, and shingles (postherpetic neuralgia). Many people with neuropathic pain experience symptoms such as depression, anxiety, problems sleeping, and memory defects in addition to pain.
For the present study, the researchers searched through previously published randomized controlled trials evaluating medications and nerve stimulation, or neuromodulation, treatments that had been administered for at least three weeks, or if there was at least three weeks of follow-up, and that included at least 10 participants per group. They identified 313 trials – 284 pharmacological and 29 neuromodulation studies – comprising 48,789 adult participants. The drug classes evaluated were alpha-2 delta ligands (⍺2δ-ligands), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and opioids. The most-studied neuromodulation treatment was repetitive transcranial magnetic stimulation (rTMS).
Drugs that are ⍺2δ-ligands, such as gabapentin (Neurontin) and pregabalin (Lyrica), target specific nerve channels that help transmit pain signals. By binding to these channels, they reduce the release of chemicals that cause pain signals to be sent to the brain, resulting in decreased pain perception. TCAs, like amitriptyline (Elavil), are primarily used to treat depression but also work by increasing the levels of certain neurotransmitters like serotonin and norepinephrine in the brain and spinal cord. These neurotransmitters help block signals while exerting a calming effect on nerve cells, which can reduce pain. Likewise, SNRIs such as duloxetine (Cymbalta) and venlafaxine (Effexor) can reduce pain by increasing serotonin and norepinephrine levels in the brain and spinal cord. Opioids like tramadol, oxycodone, morphine, and buprenorphine bind to pain receptors in the brain and spinal cord to block pain signals and provide pain relief.
The researchers used the GRADE guidelines to categorize the entire body of evidence (GRADE isn’t applied to individual studies) as either high, moderate, low, or very low. From this, they were able to come up with a list of first-, second-, and third-line treatments.
“Three medication classes were recommended for first-line use,” Ferraro said. “These were alpha-2 delta ligands (e.g., pregabalin, gabapentin), serotonin and norepinephrine reuptake inhibitors (e.g., duloxetine), and tricyclic antidepressants (e.g., amitriptyline). Importantly, these medicines have only modest benefits and require careful patient screening and close monitoring.
“We also established capsaicin and lidocaine patches and capsaicin cream as second-line therapies despite having small effects on pain – they are safe and tolerable, and suitable for use in older adults or patients taking multiple medications.”
Capsaicin is a naturally occurring compound that gives chili peppers their ‘heat.’ It works by stimulating heat receptors in the skin, tricking the body into thinking it’s overheating and triggering its cooling mechanisms. This can help reduce pain perception. Capsaicin is available as a supplement or in a cream. Lidocaine (Xylocaine), also known as lignocaine, is a local anesthetic that prevents pain transmission by blocking nerve signals.
NeuSPIG’s last set of guidelines was published in 2015. For the first time, the researchers evaluated the effectiveness of rTMS and recommended it as an appropriate treatment for selected patients. They also found inconclusive evidence for some medications and non-pharmaceutical treatments, meaning they could neither recommend for or against these treatments, which included ketamine, lacosamide and topiramate (both are anti-seizure medications), selective serotonin reuptake inhibitors (SSRIs), transcranial direct current stimulation, and spinal cord stimulation.
There was, however, a list of medications that were not recommended for use: cannabinoids, valproate (used to treat epilepsy and bipolar disorder), levetiracetam (an anti-epileptic), and mexiletine (used to treat abnormal heart rhythms, chronic pain, and some causes of muscle stiffness). The researchers said the guidelines are designed to inform and guide treatment for people with neuropathic pain.
“Neuropathic pain affects people differently, so the guideline supports the provision of high-quality patient-centered care that considers needs, values and preferences,” said Ferraro. “Treatment choices depend on potential effectiveness, safety, accessibility, comorbidities, and use of other medicines.”
Ferraro hopes that future reviews will evaluate the effectiveness of other non-drug treatments.
“High-quality evidence on treatment of neuropathic pain with non-drug treatments, such as exercise, is lacking, and should be prioritized for future research,” he said.
The study was published in the journal The Lancet Neurology.
Source: NeuRA