Motor Unit Abnormalities After Experimentally Induced Sensitization
Condition: Central Sensitisation; Motor Disorders
MeSH terms: Motor Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      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
    

Detailed description: 
      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.
    

Intervention name(s): Capsaicin Topical Cream (0.075%); Delsys Trigno Galileo System; Excaliber, Natus Medical; Placebo Cream
Intervention type(s): Drug; Device; Device; Other
Intervention description(s): Capsaicin cream will be administered as a topical skin cream; A wireless surface EMG device. The sensors will be placed on the trapezius and the infraspinatus muscle, and a recording will be performed.; Intramuscular EMG machine. The intramuscular electrode will be inserted into the trapezius and a recording will be performed.; Placebo cream will be administered as a topical skin cream
Other intervention name(s): Zostrix HP
Intervention MeSH terms: Capsaicin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A randomized placebo controlled trial using 2 treatments: 1) placebo cream 2) capsaicin cream (0.075%) (Zostrix HP)
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Central Sensitization; Surface Electromyography; Intramuscular Electromyography; Motor Unit; Recruitment