The aim of this randomized placebo-controlled study is to evaluate the effects of analgetics for neuropathic pain on mechanical hyperalgesia as a kind of evoked pain. Therefore the number of responders and non-responders on pregabalin will be evaluated in respect of mechanical hyperalgesia (stimulus-response-function (SRF) on static punctual stimuli evoking pain determined via pinprick). The hypothesis is that in the placebo group the amount of non-responders is increased.
This randomized controlled trial is intended to be the first in a series of trials that will assess the efficacy of drugs, which relieve neuropathic pain, on stimulus-evoked pain (here: mechanical hyperalgesia to static punctate stimuli). Most drugs in this class (e.g. Gabapentin or NMDA receptor inhibitors) have NNT beyond 3 in patients with chronic pain, due to a response rate of 30 to 50 %. One potential reason for this low overall efficacy might be the presence of different pathophysiological mechanisms in subgroups of patients, who suffer from the same disease (e.g. postherpetic neuralgia, diabetic neuropathy). These mechanisms may include central sensitization on one hand and peripheral degeneration of afferent fibers on the other hand. In this trial, we will use a battery of mechanical and thermal Quantitative Sensory Tests (QST), using non-nociceptive and low-intensity painful stimuli, to identify a subgroup of patients with mechanical hyperalgesia. To overcome the well-known low response rate in trials with neuropathic pain patients, an enriched design comparing active drugs with placebo will be performed, including only patients with high intensity of on-going pain in combination with mechanical hyperalgesia as sequelae of different, but well defined neurological disorders. The blinded phase of the trial will be restricted to so-called responders, i.e. patients with a clinically meaningful pain reduction of at least 30% in the primary end point (mechanical hyperalgesia). The second objective of this trial is to evaluate, whether the anti-hyperalgesic effect of the active drug is dependent on the QST profile.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
120
Berufsgenossenschaftliche Kliniken Bergmannsheil, Dept. of Anaesthesiology, Intensive Care and Pain Therapy, Dept. of Pain Therapy
number of responders and non-responders in respect of mechanical hyperalgesia (stimulus-response-function (SRF) on static punctual stimuli evoking pain determined via pinprick)
Degree of mechanical hyperalgesia
Ongoing pain (numerical rating scale)
Neuropathic Pain Symptom Inventory score
Additional QST (qualitative sensory testing) variable CDT = cold detection threshold,
Additional QST (qualitative sensory testing) variable HDT = heat detection threshold
Additional QST (qualitative sensory testing) variable TSL = thermal sensory limen
Additional QST (qualitative sensory testing) variable PHS = number of paradoxical heat sensations during the TSL Procedure
Additional QST (qualitative sensory testing) variable CPT = cold pain threshold
Additional QST (qualitative sensory testing) variable HPT = heat pain threshold
Additional QST (qualitative sensory testing) variable MDT = mechanical detection threshold
Additional QST (qualitative sensory testing) variable MPT = mechanical pain threshold
Additional QST (qualitative sensory testing) variable ALL = dynamic mechanical allodynia
Additional QST (qualitative sensory testing) variable WUR = windup ratio
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Bochum, Germany
Pain Therapy, Dept. of Anaesthesiology and Intensive Care Medicine, University of Cologne
Cologne, Germany
NOT_YET_RECRUITINGUniversity Hospital of Duesseldorf, Dept. of Paintherapy, Dept. of Anaesthesiology
Düsseldorf, Germany
NOT_YET_RECRUITINGDept. of Anaesthesiology, University Hospital of Erlangen
Erlangen, Germany
NOT_YET_RECRUITINGInsitute of Physiology and Experimental Pathophysiology
Erlangen, Germany
NOT_YET_RECRUITINGNeurological University Hospital, University of Freiburg
Freiburg im Breisgau, Germany
NOT_YET_RECRUITINGDept. of Neuroradiology, Neurological Health Care Center, University Hospital of Heidelberg
Heidelberg, Germany
NOT_YET_RECRUITINGDept. of Neurology, Neurological Section, Pain Research and Therapy, Universitätsklinikum Schleswig-Holstein, Campus Kiel
Kiel, Germany
RECRUITINGHealth Care Centre, Dept. of Neurology, Johannes Gutenberg University of Mainz
Mainz, Germany
RECRUITINGDRK - Pain Centre Mainz
Mainz, Germany
RECRUITING...and 7 more locations
Additional QST (qualitative sensory testing) variable VDT = vibration detection threshold
Additional QST (qualitative sensory testing) variable PPT = pressure pain threshold)