Muscle injections with lidocaine improve resting fatigue and pain in patients with CFS

[Kati]

Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome

https://www.dovepress.com/muscle-in...tigue-and-pain-in-p-peer-reviewed-article-JPR

Roland Staud,1 Taylor Kizer,1 Michael E Robinson2

1Department of Medicine, College of Medicine, 2Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA

Objective: Patients with chronic fatigue syndrome (CFS) complain of long-lasting fatigue and pain which are not relieved by rest and worsened by physical exertion. Previous research has implicated metaboreceptors of muscles to play an important role for chronic fatigue and pain. Therefore, we hypothesized that blocking impulse input from deep tissues with intramuscular lidocaine injections would improve not only the pain but also fatigue of CFS patients.

Methods: In a double-blind, placebo-controlled study, 58 CFS patients received 20 mL of 1% lidocaine (200 mg) or normal saline once into both trapezius and gluteal muscles. Study outcomes included clinical fatigue and pain, depression, and anxiety. In addition, mechanical and heat hyperalgesia were assessed and serum levels of lidocaine were obtained after the injections.

Results: Fatigue ratings of CFS patients decreased significantly more after lidocaine compared to saline injections (p = 0.03). In contrast, muscle injections reduced pain, depression, and anxiety (p < 0.001), but these changes were not statistically different between lidocaine and saline (p > 0.05). Lidocaine injections increased mechanical pain thresholds of CFS patients (p = 0.04) but did not affect their heat hyperalgesia. Importantly, mood changes or lidocaine serum levels did not significantly predict fatigue reductions.

Conclusion: These results demonstrate that lidocaine injections reduce clinical fatigue of CFS patients significantly more than placebo, suggesting an important role of peripheral tissues for chronic fatigue. Future investigations will be necessary to evaluate the clinical benefits of such interventions.

(Bodling mine) Comment: it goes on to say, patients are vulnerable to the placebo effect. Being desperate for treatment means people will attribute improvement to anything, including a saline injection into their muscles.

 

[RogerBlack]

The important claim is:
Fatigue (0-10 visual analog)
Before water injection, after water injection
5.5 4.7
Before lido injection, after lido injection
6.3 4.1
On this basis is the claim that lidocaine helps fatigue.

I don't believe it.
The claimed P-value is not large, p=0.03.
This is somewhat less than the 'threshold' of 0.05. so they get to claim it's real.
However, my understanding is that this only has a 5% chance of being incorrect if and only if there is reason to believe the result is 85% likely to be true anyway.

This paper has multiple negative results, which you might find logical to track together - the fact there is one outlier makes you wonder if the expectation should not be closer to 0, than 85%.

Looking at the other results, the difference in before results between the pre tests between the control and trial group is largest in this trial. Coincidence? Or indication of a flawed measurement.

If you compare the control and the trial group, and look at the measurement from the control group before, and the trial group after, you get a null result for this.

Also, the 'pain' measurement was not baseline CFS pain. It was measurement of heat induced pain.
(earlier post version swapped the numbers at the front, and made a mistaken point about what drugs the participants thought they were on, I should perhaps read more carefully at 6AM when trying to sleep )

 

[Kati]

The important claim is:
Fatigue

You mean self-report of fatigue? (Veering on sarcastic, not directed to you!)

 

[Hutan]

Yeah, but

In a double-blind, placebo-controlled study, 58 CFS patients received 20 mL of 1% lidocaine (200 mg) or normal saline once into both trapezius and gluteal muscles.

So it's worth something.

I find that ibuprofen reduces my symptoms, even stuff like the blurred vision gets better.

 

[Murph]

The important claim is:
Fatigue (0-10 visual analog)
Before water injection, after water injection
6.3 4.1
Before lido injection, after lido injection
5.5 4.7

I think you've got those numbers back to front.

 

[RogerBlack]

Yeah, but


So it's worth something.

I find that ibuprofen reduces my symptoms, even stuff like the blurred vision gets better.

Which is great - if the randomisation is perfect.

However, the effect size of the lido arm was 2.2, the effect size of the water arm 0.8.

But, the groups began 0.8 units apart, which is enough to call into question the randomisation, or experimental errors.

Relatively small errors (say the measurements being out by 0.2 in the lido group, or them being more sensitive to fatigue) would mean the significance would pop below that magic p=0.05.

 

[Murph]

The fact that they state 77% of trial participants guessed they were on the opposite arm than they were is concerning to me, I don't understand how this is possible statistically in a trial of 55 people.

I humbly suggest that is also not what the study claims:

As problems with treatment allocation concealment can influence the outcome of interventions, all participants were asked (by forced choice) to provide their best guess whether they had received lidocaine or placebo injections. Out of 30 subjects randomized to lidocaine, 24 (80%) declared having received the active study drug and six stated having received placebo.

Conversely, out of 28 subjects randomized to saline injections, 21 (75%) thought they had received lidocaine injections and seven believed to have received saline injections. A Fisher’s Z test for proportion showed no differences in the proportion of correct guesses between the groups (z = 0.46; p = 0.65).

 

[RogerBlack]

I think you've got those numbers back to front.

View attachment 22120
View attachment 22119

Corrected, sorry.
The argument was made before I copied the numbers across.

 

[Kati]

Yeah, but


So it's worth something.

I find that ibuprofen reduces my symptoms, even stuff like the blurred vision gets better.

As I bolded in my original message, it doesn't seem to matter whether they injected with saline or lidocaine, it improved pain, depression or anxiety.

 

[Murph]

Not quite in those words, but the proportion of people guessing they were in the other arm is more-or-less identical at 75% or so, and this happening in both arms confuses me.

it's ~75% saying they thought they got lidocaine, in both arms.

 

[RogerBlack]

it's ~75% saying they thought they got lidocaine, in both arms.

Thanks, deleted to avoid confusion, you are correct.

 

[Londinium]

it goes on to say, patients are vulnerable to the placebo effect. Being desperate for treatment means people will attribute improvement to anything, including a saline injection into their muscles

I'm not sure that can necessarily be attributed to patients 'being desperate for treatment'. It's known that injections provide a stronger placebo effect than pills (as do two pills over one pill, expensive pills over cheap pills and, weirdly, red pills over white pills). Indeed, I wonder [semi-unscientific speculation alert] if the pain score is affected in a similar way as one would see in acupuncture - which has been shown to 'work' not because certain points are being needled, but due to the endorphins being released upon skin puncture.[/speculation]. The strong placebo response may simply due to the nature of the sham treatment.

Other than that, I'm in agreement with those above who are sceptical that the fatigue score is really statistically significant.

 

[Valentijn]

A placebo of saline might also have some physiological effect in the injected muscle. It might help dilute or remove any lactic acid accumulation, for example, or locally improve general circulation. Those could certainly impact upon muscle pain or muscle fatigue.

 

[RogerBlack]

A placebo of saline might also have some physiological effect in the injected muscle. It might help dilute or remove any lactic acid accumulation, for example, or locally improve general circulation. Those could certainly impact upon muscle paint or muscle fatigue.

I might agree with this, if there was an indication the patients were suffering muscle pain at baseline.
There seems no indication of this, it seems solely heat-induced pain.

 

[Snow Leopard]

Unless the authors were HARKING, the primary hypothesis was the effect of Lidocaine on fatigue ratings, hence there is no need to correct for multiple comparisons. The secondary measures do require correction, but many of them were non-significant anyway - but it means the pressure pain threshold differences between drug vs saline, may be non significant for the A Trapezius muscles (in addition to the B Gluteal muscles), and there were no differences for heat thresholds. This would be an unexpected result, you would expect the drug would have an effect there.

In comparison, the same study on Fibromyalgia patients did show alterations in pain thresholds for both heat and pressure thresholds:

We have previously examined the effects of tissue injections with lidocaine on chronic pain of FM patients.21 Similar to this study, four injections into the trapezius and gluteal muscles were performed. Although lidocaine provided significant reductions of local FM pains, there was no superior effect detected for lidocaine on overall pain compared to normal saline injections.21 Similarly, no superior effects of lidocaine compared to saline injections on chronic pain of CFS patients was detected in this study. At this time, we can only speculate why lidocaine injections were only superior in reducing clinical fatigue but not pain of CFS patients. One important difference between peripheral pain and fatigue signaling may be the different magnitude of metaboreceptor and pain receptor contribution for clinical fatigue and pain in CFS, respectively. Whereas large residual nociceptive signaling of muscle groups outside of the injected areas may have prevented significant pain reductions of CFS patients, the metaboreceptor contributions of the injected muscles to fatigue may be substantial enough so that significant improvements of fatigue became detectable.

The study also shows the patients have a typical placebo response, similar to people with other illnesses.

Out of 30 subjects randomized to lidocaine, 24 (80%) declared having received the active study drug and six stated having received placebo. Conversely, out of 28 subjects randomized to saline injections, 21 (75%) thought they had received lidocaine injections and seven believed to have received saline injections. A Fisher’s Z test for proportion showed no differences in the proportion of correct guesses between the groups (z = 0.46; p = 0.65).

Hence the need for double blinded controlled trials, or objective measures!

Lastly, the fact that Lidocaine had an effect on fatigue ratings suggests that the peripheral fast voltage-gated Na+ channels play a role in perception of fatigue in this illness.

This study does not propose lidocaine as a viable treatment for this illness.

 

[pattismith]

When I had acute pains in my buttocks, I had local anaesthesics injections in my back area,
it was like I was in heaven, but it lasted only 20 mn...I would pay to feel again like I was feeling on that day!

 

[Seven7]

If you read on the side effects, nervous system is affected. I think people with OI this is bad news, I particularly get uncontrollable trembling w *caine drugs. Took me a while to figure this out, since the hospital keep insiting I was doing it "on purpse" even thought is listed as a rare side effect.

 

[trishrhymes]

I haven't read this in detail, but I get the impression that the purpose of the study was not to test a possible treatment, since short lasting injections of a local anaesthetic are not a viable long term treatment.

Rather it seems to be to get an indication of whether the symptoms of ME are peripheral or central in origin.

Taking a painkiller orally will have central as well as local effects, so you can't tell which it's working on, but using a localised treatment to two muscle areas enables them to see whether there is something peripheral, ie in the body, not the brain, that is causing the symptoms. The results seem to me to be inconclusive.

Can someone tell me whether I've understood this right?

 

[lansbergen]

Rather it seems to be to get an indication of whether the symptoms of ME are peripheral or central in origin.

That is my impression too.

 

[sdmcvicar]

For the limited value that anecdotal evidence has:

I've done this twice: once in my early 20s and once in my early thirties. Both times, it reduced my pain and allowed me to resume a schedule of running for fitness after it had become to painful/refractory to do so. In my case, the effect lasted for between 9 and 15 months.

The lidocaine has two effects as I understand it. The first, of course, is short-term pain relief. However, for the second, it seems to relax trigger points for an extended period of time in a very targeted way. Like most interventions, I think it has a temporary effect that will only be seen in some patients, but for those patients it's significant. I'd be interested to see the overlap between PWME who experience some relief from massage therapy and those who gain benefit from lidocaine injections.