Living With Chronic Pain

New Pain Treatments on the Horizon

Naturally occurring, or endogenous, opioids comprise a variety of proteins known as peptides and receptors that regulate our internal pain responses and behaviors. Drugs such as morphine, hydrocodone, and fentanyl act to mimic these responses but in the process cause significant side effects- constipation, depressed breathing, nausea, decline in cognitive abilities- and addiction. For too long they have been the go-to medication for relief leading to a worldwide crisis devastating many lives. Finding alternatives has become a priority for the estimated 1/3 of the population that suffers from chronic pain.

Pain is hard to define. For one it might be a “3” on a pain scale. For another an “8.” As a result, it complicates treatment programs and research. Are these two reports the same? If not, how, and why are they different? That’s why the National Institute for Health, NIH, established the HEAL initiative. A 50 million dollar program established to evaluate and investigate new treatment options and assess their value and validity.

Here are an exciting few on the horizon that may just fit that bill:


Scavenger receptors usually run around impeding our own naturally produced opioids, reducing their effectiveness. But when one specific scavenger receptor is blocked by a compound called conolidine, made from the pinwheel flower, it can no longer stop the amazing pain relief our own naturally produced or endogenous opioids promote.

Opioid peptides interact with, and bind to, different types of opioid receptors in both the central and peripheral nervous systems. This then triggers a cascade of reactions that lead to pain relief. But those pesky scavengers do everything possible to stop this process. One in particular, called ACKR3, binds to opioid peptides, traps them and then keeps them from binding to opioid receptors, effectively shutting down the cascade before it’s even started. Key areas of opioid activity in the brain have shown high levels of this particular scavenger.

The bark of the pinwheel flower has been commonly used in traditional Chinese, Ayurvedic and Thai medicine for decades as an analgesic. But how it achieved this action had been unknown, until now. In testing over 240 opioid receptors, Conolidine bound to the ACKR3 receptor specifically. It prevented this particular receptor from shutting down and allowed naturally produced opioids to be released.

Recently, researchers were able to make the analgesic effect even more powerful by chemically modifying the naturally occurring Conolidine and increasing its ability to bind to the ACKR3 receptor. With fewer side effects this could be an exciting new option for pain control.


With this drug, research has centered on sodium channels that sit on the surface of pain sensing neurons. These channels fire electrical signals that relay pain from peripheral nerves to the spinal cord. But sodium channels also play a vital role in how the heart, muscle and brain functions, so distinguishing those relay stations from pain ones is critical.

VX-548 is the result. In two studies of several hundred post op patients it showed better pain relief reports over hydrocodone, without serious side effects. It’s also shown promise in helping some types of neuropathic and inflammatory types of pain. Larger trials are needed but the result so far are promising.


Here at home, the University of Arizona has been researching why those with a rare genetic disorder never feel pain. That’s when they found a link to the NaV1.7 sodium channel. As described above, all nerve cells, or neurons, use electrical currents to send signals to the body and brain. Sodium channels are pivotal to a cells ability to accomplish that goal.

When a neuron is stimulated, the NaV1.7 channel opens and allows positively charged sodium ions to cross over and enter a previously negative charged cell. This change generates an electrical current and sets off a cascade of events that leads to the sensation of pain.

Dr. Khanna and his team developed a compound that successfully regulated the NaV1.7 activation, resulting in lower pain complaints. It also appeared to enhance our own endorphin production and had a synergistic effect when combined with morphine and gabapentin showing it may help in decreasing their dosages while maintaining high levels of pain relief.


Naltrexone was first developed in 1963 as an oral alternative to naloxone- the nasal spray used to reverse opioid overdoses. It has been used, off label, for years. In high doses, 50-100 mg naloxone blocks opioids. But in smaller doses NALTREZONE (0.1-4.5mg) acts by targeting glial cells, known to keep the nervous system sensitized to pain. 

As discussed in a past post, new research is showing chronic, persistent pain is thought to be due more to how our bodies responded to the inciting stimuli rather than the actual inciting event itself. Unlike narcotics, Naltrexone works at the source- the cells that cause this pain sensitizing transformation in order to shutdown the process itself. With few side effects it can play a pivotal role in pain management. But it’s not an option for those who use alcohol or opioids regularly.

Capsaicin patch

Approved by the FDA in 2009, it has been used by patients suffering from post herpetic neuralgia after a shingles infection and was recently approved July 2020 for diabetic neuropathic pain. Capsaicin is derived from chili peppers, which is what gives them their heat. Unlike over the counter capsaicin creams, research showed an 8% concentration when applied to the skin in a patch form for 30-60 minutes a day provided weeks of pain relief and improved sleep quality compared to a placebo.

And it’s generally well tolerated. The most common side effect was irritation at the application site. Use for other causes of pain are currently being studied.

A new type of neurostimulation.

Researchers in Sweden achieved a total blockade of pain in rats without affecting any other sensory or motor pathways by implanting, with exacting precision, flexible microelectrodes. This new technique should work on any type of pain that’s transmitted by the spinal cord to the brain. The electrodes specifically activated the brain’s pain control centers by blocking only the signals and pathways that transfer pain signals to the brain cortex, without activating nerve cell circuits that cause deleterious side effects.

Since a rat’s brain is similar to ours, it’s hoped this promising treatment can be transferred to humans in the next few years. But it may not stop there. Those involved also believe it may be able to help degenerative brain diseases such as Parkinson’s, epilepsy, depression and stroke victims, since it can be tailored to any part of the brain.

A short-term implanted device that dissolves

At Northwest University, scientists have engineered an implantable pain-relieving device for post-surgical pain. It has channels filled with liquid coolant and dry nitrogen that bathe the tissue and nerves cells they envelope, causing them to feel numb so pain signals are blocked. It is precisely controlled and has sensors to prevent damage and ensure the results are fully reversible. It’s small enough to wrap around a single nerve and when the job is done it’s programmed to dissolve into the surrounding tissue.

Monoclonal antibodies

During the pandemic, monoclonal antibodies were a lifesaving treatment for COVID infections. Now it seems they may also be an incredible non addictive treatment for pain relief. The National Institute of Health’s HEAL Initiative gave out $1.5 million dollars in grant money to look at this possible alternative to opioids.

They have already been approved for migraine treatments that target sodium channels. This time antibodies will prevent pain signals from transmitting by binding specifically to the sites where the transmission originates. Researchers are focused on three particular ones – NaV1.7, NaV1.8 and NaV1.9 – looking to create antibodies that fit into each like a key into a lock. This way they inhibit pain transmission but not other signals sent along the nerve.

Tarantula venom 

The same tarantula venom that causes pain and neurological dysfunction can also help nerves work better and reduce pain. A type of protein found in the venom blocks the NaV.1.7 sodium channel. But the venom also blocks muscles and brain function. Using the “Rosetta software program” and complex computer models, researchers are working to take a naturally produced peptide and redesign it into a medication that targets only pain. Many potential therapeutics are promising but they are still years away from actual use.


Recently published in JAMA was a new, safe and effective pain treatment called Pregnenolone, a neurosteroid. These are molecules made in the brain and other parts of the body that have diverse properties. One of which is analgesia.

In one study half of veterans treated with Pregnenolone reported a 50% reduction in pain without side effects. Neurosteroids may have other promising applications to treating central nervous system issues.

For those of us suffering from chronic pain there are exciting prospects in the pipeline. I’ll keep you posted on them as they develop.



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