CHRONIC PAIN MANAGEMENT AFTER HERNIORRAPHY
PREGABALIN VERSUS PLACEBO

Morbidity associated with surgical treatment of inguinal hernia is mainly
chronic postoperative pain. Despite chronic pain was thought to be rare, the
reported incidence of chronic pain in recent studies is high. In a critical
review of inguinal herniorraphy studies between 1987 and 2000 that adopted pain
as primary endpoint, the incidence of some degree of long-term groin pain after
surgery was as high as 53 % at 1 year (range, 15 % to 53 %).
According to some studies chronic pain is predominantly neuropathic in
character. Recently, as of yet unpublished data by Alfieri et al. suggest that
failure to identify the inguinal nerves is significantly correlated with the
presence of chronic pain and that the incidence of chronic pain increases
proportionally with the number of nerves undetected. Nerve damage can originate
iatrogenically during surgery or postoperatively.
In the Netherlands 32,000 inguinal hernias are corrected yearly, of which
approximately 90% is made up by males. According to a review by Poobalan et
al. yearly a minimum of approximately 5000 patients would suffer from chronic
pain 1 year after hernia surgery in the Netherlands[10]. If this new drug
proves useful, this could have a wide application.

The primary objective of this study is to investigate whether pregabalin at a
dose of 150-600 mg twice a day reduces pain in patients with chronic
neuropathic pain after herniorraphy. This research question will be answered by
testing of the following hypothesis:

- Treatment with pregabalin (150-600 mg dose) results in a statistically
significant improvement in endpoint mean pain score of >= 1,2 during 8 weeks
follow-up relatively to treatment with placebo

The secondary objective

- The difference in quantitative sensory testing (QST) thresholds between the
painful inguinal area and the normal contra-lateral side in patients of which
the chronic pain is treated by pregabalin is clinical significant greater than
the difference found in patients of which the chronic pain is treated by
placebo

Patient records are scanned for chronic pain after herniorraphy in the
participating centers. Patients that seem to match the selection criteria, are
phoned by the principal investigator to confirm the intensity, neuropathic
character of the pain and to inform the patient subsequently about the ongoing
study. Subsequently, patients are invited for an outpatient visit at the
ErasmusMC. During this visit the patient is asked for informed consent after
confirmation that the pain is of neuropathic origin by means of the LANSS score.
Thereafter the patient is randomized in two groups by the pharmacy. One
treatment group will receive a placebo while the other receives pregabaline.
Subsequently, the patients will not take any medicines for 1 week (baseline
phase) to collect our baseline data. During this phase the patients will
complete a diary reflecting their pain and pain-related sleep interference.
This diary is based on a 11-point numerical rating scale (0 = *no pain* to 10 =
*worst possible pain*; 0 = *pain does not interfere with sleep* to 10 = *pain
completely interferes with sleep*).
The medication will be mailed to the patient. After the baseline phase the
patient will start medication. The first week of medication the patients
receive 2x75 mg pregabalin or placebo. The next week the medication will be
increased to 2x150 mg. If necessary the dose can be increased the third week as
well to 2x300 mg. The phase during which data will be collected encompasses the
8 week fixed dose period after the titration period of 1,2 or 3 weeks.
Follow-up appointments will be made at 8 weeks after fixed medication is
started. Patients are free to refuse participation and choose treatment they
prefer at any moment. The number of patients found to be ineligible or refusing
to participate in the trial and the motivations/causes are recorded. Patients
in are at all times allowed to quit the trial.
Data from both treatment groups will be collected at the following points in
time: visit to research nurse; baseline phase (diary); 2 weeks (diary); 4 weeks
(diary); 8 week follow-up appointment; events. Patients who fail to keep their
8 week follow-up appointment will be given the option of a further appointment
at a more suitable date.

Patients are randomized in two groups by the pharmacy. One treatment group will
receive a placebo while the other receives pregabaline.

Pregabalin has some advances above the traditionally used drugs. It has a low
number needed to treat and an attractive number needed to harm. It can be
titrated in a relatively short period. The effect can be estimated in a
relatively very short time.