EFFECTS OF TAPENTADOL ON CHRONIC PAIN AND PARAMETERS OF CENTRAL SENSITIZATION. A PROSPECTIVE, OPEN LABEL, RANDOMIZED CROSS-OVER STUDY WITH PREGABALIN AS COMPARATOR,

Chronic pain is a serious debilitating factor for health and welfare with a
mean prevalence of 27% in the general European adult population. In most of
these conditions a cause for the pain is seldom to be found. It is speculated
that central sensitization (CS) is directly involved in the process of
chronification and maintenance of chronic pain in many conditions.
For that reason, alleviation of central sensitization should be part of the
treatment of patients with chronic pain. This has been demonstrated for
pregabalin, but in case of tapentadol it is unknown if and how it interferes
with CS. Most relevant to this study is the association of CS with chronic low
back pain, chronic pelvic pain, endometriosis, vulvodynia, and dysmenorrhea as
well as interstitial cystitis/bladder pain syndrome.
Tapentadol is a new class of opioids with a dual mechanism of function.
Tapentadol agonises the mu-opioid receptor (µ-OR) and inhibits the reuptake of
noradrenaline in the central nervous system. Its particular efficacy in
managing chronic neuropathic pain that is attributed to the latter mechanism.
The noradrenergic effect might result in modulating descending pain pathways in
the central neural system and thereby reduce or alleviate CS. Due to the low
binding affinity of tapentadol to the µ-OR (with adequate analgesic effects),
adverse effects associated with opioid usage such as
opioid-induced-hyperalgesia, gastrointestinal complications, dependency and
tolerability issues are less likely to occur.
The core of this study is to explore the effects of tapentadol on parameters of
CS in patients suffering from chronic pain. This has not been previously
performed.

The main objective is to determine the change in CS parameters upon
administration of tapentadol in comparison to pregabalin in patients suffering
from chronic pain that has a visceral or deep somatic origin.

Prospective, Open-Label, 2X2 Randomized Cross-Over.

For tapentadol we will start titrating with 50mg 2x/day and increase the dose
by 50mg 2x/day every 3 days until sufficient analgesia is reached with
tolerable adverse effects. The maximum recommended dose is 500 mg per day.

For pregabalin the start dose is 75mg 2x/day. The dose can be increased
depending on individual reaction and tolerability of the patient after 3-7 days
to reach 150mg 2x/day. If necessary, the dose can be further increased to the
maximum dose of 600 mg per day.

For the purpose of this study, included patients will be subjected to oral use
of Tapentadol and Pregabalin, completing questionnaires and a medication diary
and QST assessment.
- Tapentadol and Pregabalin:
o Expected benefits: reducing/alleviating pain.
o Expected risks and burden: insufficient pain reduction, adverse effects and
possible carry-over effects during the minimal 2 day washout period.
- Questionnaires
o Expected benefits: insight and more understanding of the nature of pain.
o Expected risks and burden: time investment needed to fill the questionnaires.
- Medication diary
o Patients will keep a daily medical diary, in which they indicate: a
painscore, whether they took medication and whether they perceived adverse
events of the medication. Furthermore, they can indicate whether additional
pain medication was necessary to relief the pain.
- QST
o Expected benefits: deeper insight into the nature of the individual*s pain by
testing the presence or absence of CS parameters.
o Expected risks and burden: short lasting pain provocation, time investment
and three extra visits to the clinic.

QST and BSE are worldwide applied and considered safe techniques. As one of the
applied stimuli measures pain
threshold and pain tolerance, a short-lasting experience of pain might be felt.
Risk that a SAE will occur is negligible.

Tapentadol and pregabalin are registered for use in Europe, the extent and
nature of their adverse effects are known and both are widely used for
neuropathic pain.