Touch; reducing pain in Parkinson patients study 1

Pain is a common problem in Parkinson's disease (PD), with 30-95% of the
patients experiencing pain. Due to changes in central pain processing PD
complicates the pain management process. Pain studies reveal that patients with
PD experience the sensory-discriminative aspects (pain threshold) as well as
the affective/motivational aspects of pain (pain tolerance) more severely than
people without PD. This is caused by overactivation of regions involved in pain
processing. Currently, 50% of patients with PD do not receive any pain
treatment, while patients who are treated with medication do not always report
a sufficient decrease in discomfort. Therefore, the development of a more
adequate treatment is important.

Recent research suggests that there may be a non-pharmacological alternative to
alleviate pain. A particular type of low threshold mechanosensory C-fibers
(C-tactile or CT afferents), appears to have a modulatory role on pain. The CT
afferent responds to gentle types of touch and provides a pleasant perception,
hence this type of touch is also called *affective touch*. CT afferents can be
activated by slow stroking, between 1-10 cm/s (optimal activation at 3 cm/s),
with a soft brush or with the hand. Interestingly, a recent study revealed that
PD patients, similar to healthy participants, report higher pleasantness
ratings for CT-optimal stroking velocities compared to higher or lower stroking
velocities. We therefore hypothesize that CT optimal touch is perceived and
processed in the same way in PD patients as in healthy controls.

The mechanisms underlying the positive effects of affective touch on pain might
be as follows. The CT afferent system activates several brain areas associated
with the motivational and subjective evaluation of touch. These areas are also
highly activated and important in the subjective appreciation of pain (pain
tolerance). Recent studies confirm that activation of the CT afferents results
in pain relief in healthy controls. There are two ways through which the CT
afferents can modulate pain processing. First, pain modulation occurs in the
dorsal horn (spinal cord) through an inhibitory connection that is related to
CT afferent input. This system prevents the pain stimulus of reaching the
(sub)cortical brain regions involved in pain processing. Second, a fMRI study
shows that the CT afferent system can modulate pain also at supraspinal levels.
When the CT afferent system is activated, it causes deactivation of regions
which play a major role in pain processing, inhibiting these regions modulates
the motivational aspects of pain. As indicated, in PD the pain tolerance is
decreased which is mostly caused by over-activation of the medial pain system.
We therefore hypothesize that CT optimal touch (affective touch) will also
reduce pain experience in PD patients.

Taken together the purpose of this project is to determine whether CT optimal
touch reduces pain experience in PD patients.

To determine whether CT optimal touch reduces pain experience in PD patients.

Current research will include two studies to answer our research question. The
first study will be addressed within this document. For the second study
another METC application will be submitted.

In this first study we will examine whether CT optimal touch, also called
affective touch (AT), as an intervention may reduce pain in PD. AT can be
activated by slow stroking, between 1-10 cm/s (optimal activation at 3 cm/s),
on the hairy part of the skin, with a soft brush or with the hand. During the
intervention study the partner or caregiver of the participant will apply the
two types of touch by using the hand.
Prior to the intervention, participants will be seen by the experimenter.
During this appointment the experimenter will provide information and will
assess possible short term effects of AT and the participant will fill in three
questionnaires. To measure the severity and intensity of the experienced
chronic pain the participant will fill in; a 11-point Likert pain scale for
itch intensity and the severity and frequency of pain will be measured by the
Kings Parkinson*s Disease Pain Scale (KPDPS). The KPDPS will be filled in
together with the experimenter. In addition, the quality of the relationship in
terms of perceived support of the participant and caregiver will be assessed
through the Quality of Relationships Inventory (QRI) short form. The QRI will
be used because the caregiver will apply the touch during the intervention, the
quality of the relationship could influence the way they apply touch or how the
participants perceives touch.. These questionnaires will be used as a baseline
measurement prior to the intervention. As mentioned, during the appointment the
experimenter will also assess the short-term effects of AT. At first to assess
possible changes in pain experience the modified Colour Analogue Scale (CAS)
for pain (affective component) and the Faces Pain Scale will be administered.
Hereafter, AT will be administered for 5 minutes by the experimenter, this will
be done by stroking the forearm of the participant with a soft brush on a slow
speed of around 3 cm/s. This is followed by a second administration of the pain
ratings. In addition, to look for any after-effects pain ratings will also be
administered after 10 minutes. This will also been done for non-affective touch
(non-AT). Non-AT will also be administered by stroking the forearm of the
participant at a faster but still quit natural speed of around 18 cm/s, this
could be compared to rubbing. The order will be randomized between patients.

Proof of concept intervention study
To assess whether application of AT in a home setting, as would be used in
the potential treatment (second study), reduces pain, first pain experience
will be measured three times a day (morning, afternoon and evening) for one
week to control for normally present pain fluctuation. One week later, half of
the participants (selected randomly) will receive AT stimulation daily for one
week followed by one week of non-AT stimulation. The other half of the
participants will first receive one week of non-AT stimulation, which is
followed by one week of AT stimulation. Stimulation will take place twice a day
(morning and evening) for 15 minutes, and is administered by the caregiver of
the patient. AT will be administered by stroking the forearm (possible effects
of AT on pain are independent of pain location) of the participant at a slow
but natural speed of around 3 cm/s. Non-AT will also be administered by
stroking the forearm of the participant at a faster but still quit natural
speed of around 18 cm/s. Both types of stroking are easy to apply and do not
involve trained therapists. Caregivers will receive instructions, so they can
apply (non)AT during the study. Recent studies also show that CT optimal touch
is quite natural to provide by close relatives.
Pain ratings will be administered before, during (every 5 minutes) and after
the stimulation.
In addition, to look for any after stimulation effects during the day pain
ratings will also be administered in the afternoon. Participants will also keep
a diary during this 3-week intervention study in which the frequency of tactile
stimulation and the experienced pain is recorded.
In addition to the effect of AT on pain, the relationship between
pleasantness ratings and stroking velocities will be further explored, to
confirm that increased pleasantness ratings are also found in this population
for AT. Pleasantness ratings will be measured during the intervention by a
visual analogue scale (VAS) for pleasantness. In addition, on the first and
last day of the stimulation the Positive Affect and Negative Affect Scale
(PANAS) will be administered.

Within this study we make use of a within-subject design. So patients will
receive affective touch and non-affective touch (placebo).

The burden consist of undergoing one week pain measurements, one week of
affective touch stimulation and one week non-affective touch stimulation. The
time investment is based on stimulating twice a day for 15 min., the total
duration of the study is three weeks. All research procedures are
well-validated and with careful screening of subjects for exclusion criteria,
participating in this research has a very minimal to no risk. Participants are
adults with Parkinson's disease, mentally able to participate and to inform
consent.