Influence of the new agent tapentadol on the perception of pain.

Tapentadol is a centrally acting analgesic with two mechanisms of action: a μ-opioid receptor agonism and noradrenaline (NA) reuptake inhibition. Although the binding of tapentadol to the μ-opioid receptor is weaker than that of morphine its analgesic action is similar to that of morphine due to the (synergistic) effect of the second mechanism (i.e., NA reuptake inhibition). NA plays a role in the endogenous descending pain inhibitory system. Especially at descending pathways NA reuptake inhibition plays a crucial role at the spinal level to reduce chronic neuropathic pain. Hence it is to be expected that tapentadol has a modulatory role on DNIC and OA and consequently will ameliorate pain in chronic neuropathic pain patients.

12-10-2013: In this double-blind randomized controlled trial, 24 patients with neuropathic pain and diabetes (DPN) were randomized to receive either a 4 week treatment with oral tapentadol (max. 500 mg oral dose per day given in two doses) or placebo. The dose was titrated up in steps of 100 mg until side effects occurred. When side effects were unacceptable to the patient the dose could be reduced. Prior to dosing the DNIC response and offset analgesia response in these patients was measured. The same tests were repeated on the last day of dosing. Prior to dosing and during treatment pain intensity scores were obtained at 1 week intervals. Inclusion criteria, exclusion criteria, primary, secondary outcomes and summary are identical to the primary study.

1. Measure DNIC and offset analgesia in neuropathic pain patients;

2. Compare DNIC and offset analgesia in chronic pain patients with DNIC and offset
analgesia in healthy volunteers;

3. Assess the effect of oral tapentadol on DNIC and offset analgesia relative to placebo and morphine.



We hypothesize that neuropathic pain patients will have abberant endogenous pain modulatory responses that will restore on administering tapentadol.

1. DNIC and offset analgesia will be measured 1 hour after administration of the treatments;

2. Spontaneous pain scores of the patient group will be evaluated 1, 3, 5 and 24 hours after intervention.

Healthy volunteers and patients will be treated with tapentadol 100mg, morphine 40mg and a placebo on separate occasions. The influence of these treatments on the endogenous control pain will be evaluated.