Cornea nerve fibre state determines analgesic response to tapentadol in fibromyalgia patients without effective endogenous pain modulation

Abstract

Background Tapentadol is a centrally acting analgesic with μ‐agonistic activity combined with noradrenaline reuptake inhibition. Its mechanism of action relies on improvement of descending pain inhibition. In the current study, tapentadol's ability to enhance conditioned pain modulation (CPM, an experimental measure of descending pain inhibition) was evaluated in fibromyalgia patients with absent or reduced CPM responses. Methods A total of 34 fibromyalgia patients completed this double‐blind trial. Patients were randomized to receive treatment with tapentadol sustained‐release or placebo for a 3‐month period with 1‐month follow‐up. At baseline, the cornea nerve fibre state (CNFS) was quantified to determine the presence of nerve fibre pathology and assess its value in the prediction of the analgesic response. Results Tapentadol significantly increased CPM responses during treatment with an average increase from baseline of 20.5 ± 12.5% (tapentadol) versus 3.0 ± 11.2% (placebo; p = 0.042). No treatment effect was observed for the absolute pain scores, however, analgesia responder rate analyses demonstrated a treatment effect in favour of tapentadol. Pain relief (a reduction in pain score ≥ 30%) was predicted by the presence of a normal CNFS (p = 0.035). Patients with an abnormal CNFS had no analgesic effect from tapentadol despite an increase in CPM. Conclusions In chronic pain patients with fibromyalgia, the increase in endogenous pain inhibition by tapentadol was translated into analgesia in patients with a normal CNFS. In those with abnormal CNFS, tapentadol treatment was without analgesic effect. Significance In this double‐blind randomized placebo‐controlled trial, we showed that tapentadol significantly enhanced the descending pain inhibition in fibromyalgia patients. Tapentadol‐induced pain relief was only present in patients with a normal CNFS.

Tapentadol treatment results in long-term pain relief in patients with chronic low back pain and associates with reduced segmental sensitization

“…The magnitude of the CPM increase (about 20%) was in accordance with previously observed increases in patients with diabetic polyneuropathy and fibromyalgia syndrome. 13 , 29 In agreement with literature, 8 we did observe a significant analgesic effect with almost 50% of patients that experienced 50% of pain relief during treatment. In contrast to our previous studies, 13 , 29 we did not observe a correlation between analgesia and CPM% responses.…”

“… 13 , 29 In agreement with literature, 8 we did observe a significant analgesic effect with almost 50% of patients that experienced 50% of pain relief during treatment. In contrast to our previous studies, 13 , 29 we did not observe a correlation between analgesia and CPM% responses. This might indicate that in patients with CLBP, pain relief is to a lesser extent or less consistently associated with CPM improvement and suggests a rather distinct mechanistic effect of tapentadol in different pain syndromes.…”

“… 8 , 9 , 37 We previously showed that tapentadol induced pain relief because of improvement or restoration of CPM responses in patients with diabetes-induced polyneuropathy and fibromyalgia syndrome. 13 , 29 …”

Association of Therapies With Reduced Pain and Improved Quality of Life in Patients With Fibromyalgia

“…Seven original trials were reported in 2 different publications each . Eleven trials (including 1203 participants) were not included in the quantitative analysis because outcome data were not reported and imputations were not possible or data indicated a skewed distribution …”

Neuropathic Pain: Challenges and Opportunities

“…Occurrence of central sensitization is a sign of an increase in disease severity. Measurement of the endogenous pain modulatory system and sensory testing, in which a variety of stimuli and tests are applied to the skin, indicate that several phenotypes of neuropathic pain exist independent of the underlying disease [5][6][7].…”