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

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.