Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy.
BACKGROUND
Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the µ-opioid receptor combined with inhibition of neuronal norepinephrine reuptake. Both mechanisms are implicated in activation of descending inhibitory pain pathways. In this study, we investigated the influence of tapentadol on conditioned pain modulation (CPM, an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus) and offset analgesia (OA, a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation).


METHODS
Twenty-four patients with diabetic polyneuropathy (DPN) were randomized to receive daily treatment with tapentadol sustained-release (SR) [average daily dose 433 (31) mg] or placebo for 4 weeks. CPM and OA were measured before and on the last day of treatment.


RESULTS
Before treatment, none of the patients had significant CPM or OA responses. At week 4 of treatment, CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses. CPM increased from 9.1 (5.4)% (baseline) to 14.3 (7.2)% (placebo) and 24.2 (7.7)% (tapentadol SR, P<0.001 vs placebo); relief of DPN pain was also greater in patients treated with tapentadol than placebo (P=0.028). Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses (P=0.78).


CONCLUSIONS
Tapentadol's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses.


BACKGROUND
The study was registered at trialregister.nl under number NTR2716.
Department of Anesthesiology, Leiden University Medical Center, P5-Q, PO Box 9600, 2300 RC Leiden, The Netherlands m.niesters@lumc.nl.
M
M
Niesters
Department of Anesthesiology, Leiden University Medical Center, P5-Q, PO Box 9600, 2300 RC Leiden, The Netherlands.
P L
PL
Proto
Department of Anesthesiology, Leiden University Medical Center, P5-Q, PO Box 9600, 2300 RC Leiden, The Netherlands.
L
L
Aarts
Department of Anesthesiology, Leiden University Medical Center, P5-Q, PO Box 9600, 2300 RC Leiden, The Netherlands.
E Y
EY
Sarton
Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
A M
AM
Drewes
Department of Anesthesiology, Leiden University Medical Center, P5-Q, PO Box 9600, 2300 RC Leiden, The Netherlands.
A
A
Dahan
D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy* / Q000503:physiopathology; D003692:Delayed-Action Preparations; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000379:methods; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017450:Receptors, Opioid, mu / Q000819:agonists; D000077432:Tapentadol; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010636:Phenols; D017450:Receptors, Opioid, mu; D000077432:Tapentadol
chronic pain, diabetic polyneuropathy; conditioned pain modulation; morphine; neuropathic pain, offset analgesia; pain, tapentadol