Central sensitisation in patients with chronic low back pain radiating to the leg

There is growing evidence for sensitisation in patients with chronic pain.
Continuing nociceptive inputs can induce a reduction in threshold and an
increase in responsiveness of peripheral nociceptors, i.e. peripheral
sensitisation, which on itself may lead to a prolonged increase in excitability
and synaptic efficacy of neurons in central nociceptive pathways, i.e. central
sensitisation. Several methods are advocated to measure central sensitisation.
For example, quantitative sensory testing (QST) is a psychophysical method that
objectively measures responses to calibrated graded innocuous or noxious
stimuli and represents, in most respects, an extension of the routine
standardised sensory measurements. Furthermore, central sensitisation can be
assessed with the Central Sensitisation Inventory (CSI). For treatment of
severe cases of chronic low back pain, patients are referred to
multidisciplinary pain clinics for further assessment. If the diagnosis in
patients with chronic low back pain radiating to the leg (CLBPr) is not clear
despite extensive physical, neurological, orthopaedic and radiological
examination, a precision diagnosis, such as diagnostic segmental nerve root
block (dSNRB), has been advocated. After a positive dSNRB, possible
interventions are therapeutic SNRB (tSNRB) or pulsed radiofrequency (pRF). The
extent of central sensitisation in patients with CLBPr, its role in
chronification and its interaction with diagnostic and therapeutical
interventions are unknown up to now.
Therefore, the main questions of this study are: can we find signs of central
sensitisation in patients with CLBPr? Can we quantify it? Do the interventions
(tSNRB and pRF) normally applied in care as usual affect central sensitisation?

To determine the presence or absence of central sensitisation in patients with
CLBPr and to determine the effect of segmental nerve interventions on central
sensitisation.

Study design
Observational study in 50 patients with chronic low back pain radiating to the
leg (CLBPr) and 50 sex- and age-matched healthy control subjects.
Patients will be screened for this study at the Spine Center Groningen or at
the UMCG Anesthesiology Pain Center (APC). Leg pain must be higher than back
pain in those patients.
Patients will receive care as usual. Diagnostic and therapeutic SNRBs, as well
as pRF, will be performed according to the standard procedures of the APC (see
appendix 1 - Wortelblokkades: diagnostische, therapeutische en radiofrequente
behandelingen op cervical, lag thoracaal, lumbaal en sacral niveau)
Healthy control subjects (colleagues, friends and friends of the patients) will
also be screened for this study at the Spine Center Groningen or at the APC,
but will not receive any diagnostic or therapeutic nerve block. They will
undergo all the measurements (BSE, QST and questionnaires as described below).
Patients and healthy control subjects who fill the inclusion criteria will be
given written information about the study. After a few days, a member of the
research team will call the participant to ask whether they have any questions
and want to participate. If they agree in joining the study, they will be asked
to return the informed consent. Upon arrival of the informed consent,
participants will be invited to the hospital and receive the questionnaires
that are relevant for the first visit (healthy controls will not receive the
drawing pain area). They are asked to fill in these questionnaires before they
come to their appointment in the hospital. Before each next visit, relevant
questionnaires will be sent and participants are asked to fill them in the day
before the appointment.
The intervention provided in this study is the same as the standard
intervention provided at the APC and follows the guideline for segmental nerve
root block (see appendix 1 for the detailed procedure). This
treatment/intervention is routinely applied at the APC and is part of the
Medisch Handboek Afdeling Anesthesiologie of the UMCG.
QST, CSI, PCS and PVAQ are not part of CaU, they are specifically included in
this protocol for the purposes of this study. Together, these items take about
25-30 minutes to be performed.


Visit 1 = t1
At their first visit (t1), patients will undergo dSNRB. This procedure is part
of CaU and will not be compensated. Healthy control subjects will not undergo
dSNRB, but will pass through the measurements; they will be compensated (see
item 11.6 - Incentives).
Before the block, we will assess: QST 1 and BSE. Relevant questionnaires that
are assesed the day before are: CSI, NRS, PCS, PVAQ, DPA, SBST SF-36, PDI and
WAI. During the block, we will assess: voltages of sensory and motor electrical
nerve stimulation and mapping paresthesias (see local protocol for
wortelblokkades - appendix 2). Within 2 hours after the dSNRB, we will apply
the NRS back and NRS leg.
Some patients may undergo more than one dSNRB at various spinal levels, which
will be performed about one week apart of each other (3 dSNRBs are the
maximum). In case another diagnostic block is indicated, this t1 procedure will
be repeated (and called t1a, t1b). Relevant questionnaires for these visits are
the CSI and NRS scores.

In case of a pain reduction >= 50%, the patient is considered a *positive* and
goes to the therapeutic intervention, about one week after the last dSNRB. The
responsible physician will decide which intervention this patient will receive
(part of CaU).
In case of a pain reduction < 50%, the patient is considered a *negative* and
excluded from the study. This patient also goes to the therapeutic
intervention, about one week after the last dSNRB. The responsible physician
will decide which intervention this patient will receive (part of CaU).

Visit 2 = t2
One week after the dSNRB, the second visit takes place (t2). During this visit,
patients will receive one intervention: tSNRB or pRF.
This procedure is part of CaU and patients will not be compensated.
Before the intervention, we will perform the following measurements: QST and
BSE. Relevant questionnaires that are assesed the day before are: CSI and NRS.

Visit 3 = t3
About four weeks after the intervention, the last visit will take place (t3).
The following measurements will be performed: QST, BSE, CSI, PCS, PVAQ, SBST,
VAS back/leg, drawing pain area (for patients), SF-36, PDI and WAI.
QST, CSI and BSE will be measured 4 weeks later, because we are not interested
in the acute pharmacologic nerve block agent effects, but in the late effects
of CS.
This last visit is not part of CaU and the patients will be compensated if the
appointment cannot be scheduled together with a regular visit (see item 11.6 -
Incentives).
For a summary of the study design, see flowchart on page 17. The grey items are
additional to care as usual.

Duration
Depending on the amount of dSNRBs performed, the duration of this study for the
patient will take between 5 to 7 weeks.
Data collection will take 1 year.

Setting
UMCG Anaesthesiology Pain Centre, at Beatrixoord, in Haren.

QST and BSE are worldwide applied and considered safe techniques. Since 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.
Benefit: for patients, participation may be considered more advantageous since
the schedule of procedures planning is faster than normal.