Fact-check of stem cell therapy for pain & neuropathy

Does it make any sense medically or scientifically to use stem cell therapy for pain or neuropathy?

There isn’t much solid evidence that this is a good way to go. However, there’s a vast scope of research ongoing in this area. Stem cell clinics have been earning millions of dollars selling this idea too.

The goal of today’s post is to fact-check this area.

What’s in this article?

Stem cell therapy for pain? | Supposed rationales for stem cells for pain | Nerve function & neuropathy | Location, location, location | Clinical trials and data | Looking Ahead | References

Stem cell therapy for pain?

The whole idea of stem cells for pain has been on my mind for several reasons.

The other day I went to the dentist for a tooth issue and I ended up getting three shots of novocaine for the pain. Ow!

In the middle of all of this I chatted with her about how novocaine works. She knows I’m a scientist.

Does the novocaine have to be injected in a targeted way to a specific nerve or nerves? Yes it does. She went on to explain about the nerves involved.

Interesting stuff to ponder and a good distraction as I was on and off in some pain. And, of course, stem cells came to mind as I was sitting in the dentist’s chair.

I’ll come back to this story later.

Also, this all is on my radar screen as it seems like even more stem cell clinics are marketing unproven stem cell therapies at a high price specifically for pain relief lately.

Clinic people are even having conferences on this concept. See the email ad I got a couple of years back on one such conference below.

I also just saw a 2020 paper on a small, double-blinded study that suggested some pain relief might be possible using MSCs, but it has issues (more below).

Is there any FDA-approved stem cell-based treatment for pain? Not yet.

In Leigh Turner’s and my paper on stem cell clinics in Cell Stem Cell in 2016, we found in our data analysis that marketing of stem cells for pain was the 2nd most common claimed condition (see Figure 2B below).

If you also consider neuropathy and other kinds of more specific pain-related conditions, the numbers go even higher. I believe classified neuropathy in this analysis as “Neuro” instead of “Pain”.

Supposed rationales for stem cells for pain

Circling back, does it even make any sense scientifically that stem cells or related products like platelet right plasma (PRP) could relieve pain specifically?

How could this work? One way is by fixing damaged tissues or reducing inflammation.

A damaged tissue such as a knee joint, if repaired by stem cells, could be less painful.

But unfortunately repair of knee or other damaged joins and cartilage using stem cells or PRP is not really proven to work yet. No real repair means no real pain relief beyond a temporary placebo effect.

Nerve function & neuropathy

What about repairing nerves? Damaged or malfunctioning nerves can cause pain, which is often what is going on in neuropathy. The nerve can keep sending out signals when it shouldn’t.

In theory stem cells might be able to repair, replace, or supplant dysfunctional nerves leading to less pain. But most commercial clinic offerings in this area aren’t using the right kind of materials to address nerves. It’s not clear to me how, for instance, adipose stem cells could repair nerves.

They are not programmed to do this.

Also, if they are injected IV, the odds of repairing a specific joint make even less sense. The data isn’t clear for bone marrow stem cells either.

One more specific mechanistic idea is that stem cells might secrete growth factors that lower inflammation or calm overactive nerves. The same kind of rationale is given for PRP, which is essentially a growth factor concentrate.

Repairing a damaged spine with stem cells might also lead to less pain either in the back or somewhere else in the body.

Location, location, location

But getting back to my experience with novocaine at the dentist, how do you get the right stem cells to the right place in the spine and have them do the right thing (and not the wrong thing) to fix the nerve or spine in such a way to reduce pain? It’s not simple.

If stem cells do secrete anti-pain factors, you cannot expect any benefit for a specific source of pain (like a damaged knee) if you just inject stem cells or exosomes or PRP into the blood systemically. Would systemic novocaine help your tooth pain?

I doubt it. And I bet there’d be side effects.

In fact, just injecting novocaine in your mouth at the dentist in a place slightly too far from the nerve involved in the pain might not help you much either. The same kind of principle applies to stem cells for pain. Also, even if you inject in the right place for any given pain, how do you know the dose of stem cells is right? Pain varies a lot from day to day. I had to get 3 shots of novocaine when usually only one or two do the trick. Why? It’s hard to say.

The spine might be a logical place to inject stem cells or cells made from stem cells for certain kinds of pain.

A 2020 mouse study in the journal Pain out of  Australia  reported that a specific class of neuron made from iPS cells could relieve pain in mice after transplant.  Here’s the basic takeaway from this paper:

“A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Here, we show that terminally differentiated hiPSC-derived GABAergic neurons alleviate neuropathic pain.”

It’s unclear how relevant this is to people, but it’s an exciting direction. Still, I wouldn’t want a stem cell clinic injecting anything into my spine. Too dangerous!

Clinical trials and data

What do the human trial data tell us so far?

There are loads of clinical trials here, but not much solid data.

I found listings for 785 clinical trials for stem cells at least somehow related to pain now in 2022 search on Clinicaltrials.gov. Hopefully some of these will provide clarity on this hot topic in the future.

Remarkably, my research found that the number of pain-related clinical trials of this kind has more than doubled in just four years.

What about the 2020 paper I mentioned earlier reporting some possible benefit? The good news is that it was double-blinded.

Yet the authors themselves point out quite a few limitations to their study. It was not placebo-controlled. Also, the groups were very unbalanced in their baseline characteristics, probably due to the small size of the study. So, it’s inconclusive. Biomedical science and clinical trials is hard and involves a lot of repetition with tweaks.

Looking ahead

Overall, I believe that the real lesson from that paper is that more, larger studies are needed.

I didn’t find much encouraging, quality clinical trial data on PRP for pain either in the literature.

In a general sense, stem cells and related biologics just are not proven effective for pain and there remain safety risks.

Perhaps the outlook will be different in 5-10 years.

What to do about pain now? One of the most common questions I hear from patients asking for input on stem cells (who I remind that I’m not an MD and so cannot give medical advice) is in regard to pain. Waiting is sometimes not realistic.

It’s a good but tough question in thinking about going beyond what medicine now has to offer. Bear in mind that the clinics out there are trying to make money selling pain relief that maybe isn’t real or lasting.

What many of them are selling could make things much worse too.

References

1. Clinicaltrials.gov search on April 6, 2022 for trials related to stem cells for pain.
2. PubMed search results for articles with “stem cells” and “pain” in the title on April 6, 2022. I used a clinical trial filter.
3. Intra-articular injection of culture-expanded mesenchymal stem cells with or without addition of platelet-rich plasma is effective in decreasing pain and symptoms in knee osteoarthritis: a controlled, double-blind clinical trial, R. Bastos, et al., Knee Surg Sports Traumatol Arthrosc, 2020.
4. Cleveland Clinic resource on neuropathy.
5. Human induced pluripotent stem cell-derived GABAergic interneuron transplants attenuate neuropathic pain, Pain, 2020.
6. Also see this post on stem cells for knees cost.

Note that I do not mean this post as medical advice. Talk to your doctor about medical decisions.