Clinical phenotyping of postherpetic neuralgia patients to optimize pain treatment.

Rationale: One of the four most prevalent neuropathic pain syndromes is herpes
zoster induced pain, also called postherpetic neuralgia (PHN).1,2 Patients
suffering from PHN typically describe different types of pain sensations and
the disease is frequently severe, debilitating and difficult to treat.3-5
Subsets of PHN patients have different underlying mechanisms responsible for
the generation and maintenance of their pain.6 Recently, three different
clinical phenotypes of PHN have been identified using quantitative sensory
testing (QST), yet these phenotypes still overlap within 28% of patients and in
30% of patients no clinical phenotype can be assigned indicating phenotyping
needs to be improved.78 There are indications that these different clinical
phenotypes assessed with QST respond differently to existing treatment regimes.
More research is needed to improve the accuracy of clinical phenotyping and
relate differences in efficacy of existing treatment regimens to the clinical
phenotypes.

Objective: The primary objective is to improve defining clinical phenotypes of
PHN patients using the following diagnostics; questionnaires, QST, blood and
cerebrospinal fluid (CSF) assessment and skin nerve fiber density measurements.
The secondary objective is to assess the efficacy of existing treatment
regimens for the different clinical disease phenotypes of PHN at one year
follow up.

Study design: Observational study

Diagnostic study procedures: Patients with pain after a herpes zoster infection
referred to the pain clinic of the UMCU receive care as usual (including intake
questionnaires and QST during their first visit). Patients who give informed
consent will be asked to undergo one vena puncture for 20 ml blood withdrawal
and two skin biopsies of 3 mm diameter each. Additional informed consent will
be asked for a one time CSF withdrawal and MRS. A second QST measurement is
performed at one year follow up.

Benefit: Patients will receive care as usual and have no direct benefit of
participation in the study. Results will elucidate if different disease
phenotypes can be distinguished and if these phenotypes predict efficacy of
pain treatment for PHN patients. Potentially a better understanding of the
underlying pathophysiological mechanism of PHN is obtained. Obtained knowledge
of symptom- or mechanism based therapies will be applied to future patients.
Burden: As part of standard care patients fill in questionnaires (Vragenlijst
midden Nederland, DN4, HADS, PCS, SF12, TSK) before their first visit and six
months after their first visit (BPI, DN4, GPE, HADS, NRS, PCS, SF12, TSK). A
QST measurement is performed during their first visit. As part of research, a
patient will have two extra scheduled visits after giving informed consent.
During the first visit one blood sample (20 ml), two skin biopsies (3 mm
diameter each) and in those patients that have given informed consent for CSF
withdrawal (3 ml), a spinal puncture will be performed in a day care setting.
If patients have given informed consent of MRS imaging, we will aim to combine
the appointments. The sample taking procedures will take maximally 30 minutes
in total and MRS imaging will take 30 minutes. One year after the initial visit
the patients are asked to fill in the following questionnaires (BPI, DN4, GPE,
HADS, NRS, PCS, SF12, TSK) and undergo a second QST measurement. Travel
expenses will be compensated for the extra two scheduled visits.
Risks: The collection of blood and the skin biopsies have negligible risks. The
collection of CSF has a negligible risk of infection or post-spinal headache.
Non-invasive MRS imaging has negligible risks and for patient* safety a
standardized MRS checklist will be used to ensure safety.