Validation study: a newly developed neuropathic pain Heat-Capsaicin-Warmth (HCW) sensitization model.

The effects of a single oral administration of gabapentin (trade name
Neurontin®) and infusion of remifentanil (trade name Ultiva®) will be studied
in a newly developed pain model.

Gabapentin is a registered drug for epilepsy and neuropathic pain. The exact
mechanism if action is unknown. It's therapeutic action on neuropathic pain is
thought to involve binding to certain (calcium) channels in the central nervous
system.

Remifentanil is a registered drug that is already being used for many years at
hospitals during surgery. Remifentanil is an opioid like drug which is ultra
short-acting. You will receive the drug and the placebo by intravenous
infusion. The infusion takes about 45 minutes. Since administration of
remifentanil in an effective dose very likely unblinds the subject due to side
effects, an active placebo infusion will be used, i.e. diazepam.

The above drugs will be administered to test a pain model, at which well
tolerated pain stimuli will be administered. As part of the pain model,
capsaicin cream will be applied on your skin of your underarm. Capsaicin is a
cream which will cause a heath sensation of the skin and induces redness of the
skin. Capsaicin cream consists of an extraction from red pepper.

Primary:
Part I:
- to determine the effects of gabapentin and remifentanil on the evoked area of
hyperalgesia, area of allodynia, pinprick hyperalgesia and background pain
using a newly developed HCW sensitization model
Part II:
- to determine reproducibility of the model with a washout of 14 days

Secondary:
Part I:
- to assess the safety and tolerability of the HCW sensitization model
- to assess the safety and tolerability of a single oral dose of gabapentin and
remifentanil

Design:
A randomized, double-blind, placebo-controlled, three-way crossover study with
a washout of fourteen days.

Procedures and assessments
Screening:
Familiarization with study procedures, medical history, allergy check for
capsaicin and responsiveness test, demographics, in and exclusion criteria,
previous and concomitant medication, physical examination and clinical
laboratory (clinical chemistry and haematology).

Follow-up:
- adverse events

Observation period:
Part I: three ambulatory visits
Part II: three ambulatory visits

Pharmacodynamic assessments:
Measurements of secondary hyperalgesia by von Frey filament (64 mN rounded
tip), measurements of tactile allodynia by standardized brush, hyperalgesia by
pinprick and monitoring of background pain using visual analog scale (VAS)
scores and Bond and Lader VAS; mechanical (pain) detection thresholds
post-gabapentin/placebo dose in Part I.

Safety assessments:
AEs throughout study; continuous monitoring of oxygen saturation, heart rate
and rhythm, blood pressure and respiratory rate from 55 minutes pre-dose until
40 minutes post end infusion.

Procedures: pain, light bleeding, heamatoma, possibly an infection.