The study, titled “Cornea nerve fiber state determines analgesic response to tapentadol in fibromyalgia patients without effective endogenous pain modulation,” was published in the European Journal of Pain.
Tapentadol is an analgesic medication that works by affecting the opioid receptors, and the hormone noradrenaline, within the body. Its specific mechanism of action relies on improving “descending pain inhibition,” which is experimentally measured by a technique called conditioned pain modulation (CPM). In essence, this is the concept that one stimulus can override another, creating the so-called “pain-inhibits-pain” effect.
In this study, researchers assessed the effect of tapentadol on CPM. Fibromyalgia patients who were experiencing chronic pain were given either tapentadol (15 people) or a placebo (19 people) for three months. They were assessed monthly throughout the treatment, and also one month after treatment.
CPM was measured via a test that involved, essentially, having cold pain applied to the person’s foot, and measuring how this overrode heat pain that was applied at the person’s arm. Additionally, patients’ levels of spontaneous pain were assessed via a questionnaire.
Treatment with tapentadol increased patients’ CPM scores by an average of 20.5%. There was no significant difference from baseline, on average, in those given a placebo. Although the score increased, this is in fact suggestive of less pain — it can be thought of as “more inhibition of the original pain.”
Spontaneous absolute pain did not differ between the groups, on average. But the researchers noted a trend toward those who were given tapentadol being more likely to have some response, however large or small.
The researchers then looked in more detail at the patients who received tapentadol to determine who did or did not have substantial pain relief, which they defined as a CPM score increase of at least 30%.
Using a technique called cornea confocal microscopy (CCM), the team examined the nerve fibers in patients’ corneas (part of the eye), which can be an indicator of more general nerve damage, or lack of damage. Interestingly, the researchers found that patients who responded well to tapentadol tended to have normal CCM images (8/9 people), whereas those with abnormal CCM images (1/6 people) were much less likely to respond to the therapy.
Given the results, the scientists advise that, although there seems to be an indication for this drug in people with fibromyalgia, only a subset of patients would actually benefit from this treatment.
“Further studies are required to expand the process of phenotyping [grouping patients according to characteristics] and assess whether phenotyping will lead to a reduction in the opioid adverse effects including (and most importantly) addiction and respiratory depression,” they said.
“In summary,” the researchers said, “we observed that tapentadolin contrast to placebo significantly increased the efficacy of the descending inhibitory pain pathway as measured by CPM. Patients with a normal cornea fiber state had an increase in CPM and displayed pain relief during tapentadol treatment. In contrast, patients with an abnormal cornea nerve state had no pain relief from tapentadol despite an increase in CPM.”