Central Sensitisation Clinical Trial
Official title:
Evaluation of Motor Unit Abnormalities After Experimentally Induced Sensitization Using Capsaicin: A Randomized, Double-Blinded, Placebo-Controlled Study
Central sensitization is a condition that represents a cascade of neurological adaptations, resulting in an amplification of nociceptive responses from noxious and non-noxious stimuli. This phenomenon presents itself in a vast majority of chronic pain syndromes. Previous evidence has shown that central sensitization results in afferent nociceptor and dorsal horn abnormalities; however, a link between whether this abnormality translates into motor output and more specifically, ventral horn abnormalities, needs to be further explored. Twenty participants were recruited and either a topical capsaicin or a placebo topical cream was applied to their back to induce a transient state of sensitization. Surface electromyography(sEMG) and intramuscular electromyography(iEMG) were used to record motor unit activity from the trapezius and infraspinatus muscles before and after application of capsaicin/placebo. Motor unit recruitment and variability were analyzed in the sEMG and iEMG respectively
Central sensitization describes a state of neuronal hyper-excitability in the central nervous
system that may occur due to malfunction of spinal and supraspinal pain facilitatory and
inhibitory circuits resulting in amplification of somatosensorial responses. Beyond
somatosensorial changes, alteration in motor function can also be present with pain, and may
be a reflex of neuromuscular function impairment. A normal afferent input and normal central
processing circuitry is essential to deliver normal efferent output. However, the influence
of the changes that occur within the dorsal horn on the ventral horn remain largely ill
defined.
Motor unit assessment is crucial in evaluating diseases and abnormalities within the ventral
horn. Activity of the ventral horn, where anterior horn cells reside, is very important for
motor unit activation. Surface EMG (sEMG) and intramuscular EMG (iEMG) can be used to assess
the neural drive to muscles, by recording motor units to understand the effects of central
sensitization on motor control and the ventral horn. Based on Henneman's size principle,
motor units should be recruited in the same order, with smaller units being recruited first.
This principle presents an opportunity to investigate if central sensitization creates
abnormalities on the motor unit level.
Previously, central sensitization has been induced in healthy subjects to examine its
neurophysiological effects via capsaicin. Capsaicin, a chilli pepper extract, can be used to
effectively induce experimental transient states of central sensitization. The presence of
expanded sensorial responses and the involvement of the spinal nociceptive system post
capsaicin have been largely tested by means of quantitative sensory testing methods and
electromyography (EMG).
Despite the usefulness of experimental capsaicin to better understand the sensorial
abnormalities, its impact on motor function and motor unit recruitment are lesser studied.
Evidence suggests that nociceptive input by peripheral capsaicin exerts a centrally-mediated
inhibitory effect on motor function. A decrease in root mean squared (RMS) amplitude during
exercise at the time of peak sensitization was measured by needle EMG. However, the effect
that capsaicin-induced sensitization has on individual motor units or on their recruitment
patterns has not been previously examined.
The purpose of this study was to determine whether topical capsaicin-induced sensitization
has any influence on ventral horn activity. We hypothesize that capsaicin induces a change in
individual motor unit activity, as well as the recruitment pattern of many motor units, and
may affect motor unit activity at different segmental levels from the level of capsaicin
application.
Participants:
Twenty-three healthy participants, age between 20-70 years old, with no direct trauma to
cervicothoracic region within the past 30 days, no past medical history of inflammatory
disorders as rheumatoid arthritis, no neurodegenerative disorders such as Parkinson's disease
nor motor neurone diseases as amyotrophic lateral sclerosis, or other neuromuscular disorder
were recruited for this study. Also, included subjects had a normal body mass index (18.5 -
24.9) and had a pain visual analogue scale (VAS) below 3 indicating low pain severity. Since
prevalence of neck pain in the general population is high, mild pain or aches are not
necessarily related to an abnormality of the underlying muscle. Participants had to be able
to communicate in English. Participants were excluded if they had persistent pain for more
than 3 months.
Experimental Protocol:
An initial screening was performed to assess eligibility in the study. Each participant was
seated upright with their hands comfortably on their lap and asked to relax their neck and
shoulder muscles. The physician member of the research team then assessed the patients' pain
intensity by visual analogue scale (VAS). VAS ranges from 0 to 100 mm which 0 mm reflecting
no pain at all and 100 mm representing the worst imaginable pain. Following this, brush
allodynia, a clinical technique used to identify pain due to a stimulus that does not
normally provoke pain, was performed to confirm presence of central sensitization. To map out
borders of secondary allodynia, subjects were instructed to recognize a distinct alteration
in the sensation perception such as increased burning, intense pricking, or an unpleasant
sensation, and that location was marked. Brush allodynia score (BAS) was calculated as the
distance between the farthest points marked on the superior and inferior axis multiplied by
the distance between the farthest points marked on the medial and lateral axis as previously
described by Cavallone et. al. The VAS and the presence of central sensitization by means of
BAS were assessed at baseline (pre) before the induction of sensitization and twenty minutes
after (post).
Upon successful screening of inclusion and exclusion criteria, participants had their left
side area of skin (overlying the upper trapezius and infraspinatus muscles) cleansed with
alcohol preparation pads and water. The skin was abraded with '3M Red Dot' abrasive strips
before application of the surface electromyogram (Trigno Galileo sensors, Delsys Inc.).
Electrodes were placed in 4 areas: the muscle belly of the upper trapezius, and the
infraspinatus, as well as reference electrodes on C7 and the acromion. These electrodes were
4 channel EMG sensors and had their signals filtered from 20 - 450 Hz. The sEMG recordings
were wirelessly transmitted to the Trigno base station, which relays and compiles the data to
Neuromap (Delsys Inc.) for signal analysis. A monopolar needle electrode was inserted into
the upper fibers of trapezius muscle and its reference was placed at the mid-clavicle point.
Using this setup intramuscular recordings of single motor units were performed using an
Excaliber, Natus Medical clinical electrodiagnostic machine.
Electromyograms recordings before application of intervention
Participants were instructed to perform horizontal shoulder abductions from 0° to 90° and
then from 90° to 0° for 1 minute. The study subject was verbally cued to move their arm every
2 seconds. sEMGs were recorded during this time. Upon completion of this task, a monopolar
intramuscular needle electrode was placed directly into the upper trapezius muscle.
Participants were then instructed to gently contract their trapezius muscle by shrugging
their shoulder, enough to recruit only the first motor unit in that region. Visual feedback
of the signal was given to the subject to ensure that only the first motor unit was activated
for the movement. The signal from this motor unit was then optimized for initial deflection
from baseline and amplitude characteristics before recordings were made. iEMG recordings were
recorded for 30 seconds at a sampling frequency of 6 kHz.
Application of intervention
Participants received either a dose of 2.5 ml (75µg/ml) capsaicin cream (treatment, Zostrix
brand) or skin lotion (placebo) which was inert and caused no sensitization effects.
Participants were also blinded to the delivered treatment, using concealed containers for the
creams. The location of application was a 10 cm by 10 cm square on trapezius muscle which
extended from T3 to T8 on the left side that all recordings were conducted.
After collection of the baseline sEMG and iEMG recordings, a trained medical professional
applied the capsaicin / placebo cream directly to the region of skin in a standardized 10 cm
x 10 cm square at the spinal levels T3-T8, to sensitize the nociceptive afferents within that
region. A twenty-minute waiting period was used to enable the sensitizing effects of
capsaicin to take effect.
Electromyograms recordings after application of intervention
To confirm the presence of central sensitization, brush allodynia was used to detect
mechanical allodynia outside the region of the primary nociception - region of topical
placement - which is the region of secondary allodynia. Upon confirmation of central
sensitization, in participants with application of topical capsaicin, participants were
entered into the experimental arm of the study.
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