New treatment offers hope to end the pain of neuropathy for millions
For people suffering from the burning, tingling and shooting pain of neuropathy, current treatments are limited and often fail to bring lasting relief.
But help may be on the horizon.
Northeastern University researcher Ganesh Thakur says his lab has developed new classes of drug compounds that harness the body’s own pain control systems to reduce the nerve pain, inflammation and swelling associated with neuropathy.
Instead of masking symptoms, his lab’s discoveries leverage the body’s own signaling systems to offer relief without the sedation, cognitive fog, or risk of addiction associated with opioid analgesics—which have less than a 20% efficacy rate in treating neuropathic pain, says Thakur, a professor of pharmaceutical science.
“Nerve pain remains one of the most difficult and persistent forms of pain to treat, but new drugs from Northeastern are giving hope for gentler, more effective relief,” Thakur says
“This research could help millions reclaim their lives from pain.”
What is neuropathy?
Thakur and colleagues at his drug discovery lab were working on non-opioid treatments for different pain conditions when they discovered that fine-tuning two types of natural pain controls in the body worked especially well for chronic pain and neuropathy.
“Normal pain happens when your body gets hurt and nerves send ‘ouch!’ signals to your brain,” Thakur says.
Neuropathy, also known as chronic nerve pain, is different, he says. “It’s when nerves go haywire and send pain messages even when there’s no injury, like a broken alarm going off all the time.”
The nerve damage is often associated with diabetes, infections and cancer treatment, but it can also be hereditary.
Why neuropathy is hard to treat
“Each person’s nerve pain is different and hard to target — what helps one person may not help another,” Thakur says. “The nerve damage is coming from multiple pathways. It’s complex, and no single medication effectively addresses it.”
“Ordinary pain drugs such as aspirin, ibuprofen or even strong opioids usually don’t work well,” he says. “They aren’t built for the messy, mistaken signals from injured nerves.”
Topical creams help numb local nerves but don’t help deep or widespread pain, and anticonvulsants that calm down electrical signals can make users sleepy or dizzy.
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“This is why scientists are searching for safer, smarter solutions,” says Thakur, whose lab is charting a new course in the search for safer pain treatments, backed by nearly $6 million in National Institutes of Health funding.
Harnessing the power of endogenous cannabinoid and nicotinic pathways
What Thakur’s lab discovered is that fine-tuning natural pain-blocking chemicals in the body’s endocannabinoid system reduces nerve and inflammation in animal models.
And it does it without grogginess, withdrawal or inducing the high that comes from the THC in marijuana.
The prototype cannabinoid compound is GAT211, and the goal is to make a pill that can boost pain-relieving signals in a process called positive allosteric modulation, Thakur says.
“You’re turning up the endogenous cannabinoid’s signal to reduce the pain,” he says. In particular, the researchers are looking at firing up two primary cannabinoid receptors, CB1 and CB2 using novel dualsteric modulators, which Thakur says is a novel approach.
“The (damaged) nerve is sending signals to the brain and spinal cord that ‘there is damage, cure it,’” Thakur says. “The cannabinoids block that signaling pathway and also control inflammation.”
In addition, the team is studying a new class of compounds known as “ago-PAMs” of the alpha7 nicotinic receptor, exemplified by GAT107, which both activates and positively modulates the receptor to reduce nerve-driven inflammation and pain signaling.
“It is a nicotinic receptor allosteric modulator, meaning it fine-tunes specific nicotinic acetylcholine receptors involved in pain and inflammation, but unlike nicotine, it does not stimulate the brain’s reward pathways and is therefore not addictive, Thakur says.
“Both compounds, GAT 211 and 107, are analgesic and anti-inflammatory. They tune up the body’s response.”
Clinical trials
“These are early-generation compounds,” Thakur says. “We want to produce more potent and selective compounds with drug-like properties.”
He says that he hopes to be ready for clinical trials on humans in four to five years.
“It’s a powerful validation that the NIH has recognized more than 15 years of groundwork at Northeastern by awarding us two major R01 grants,” Thakur says. “Together with the two R01s, the lab was also awarded a third R01 grant (about $3.5 million) focused on designing novel compounds to treat nicotine addiction and substance use disorders.”
“Collectively, these awards highlight both the breadth of the lab’s translational impact and the NIH’s confidence in its research trajectory,” he says.
“It took us more than a decade to fully unravel the mechanisms behind these compounds, but we now have patents, strong preclinical efficacy in animal models of pain, and are advancing toward optimized molecules,” Thakur says.
“Most recently, the mechanism of action of GAT107 was deciphered and published in Cell” in February 2024, he says. We’re in a strong position — and I’m optimistic these therapies will evolve into real options for patients.”
