A New Experimental Model of Transient and Short-lasting Muscle Pain in Humans Based on Diathermy

Musculoskeletal Pain Clinical Trial

Official title:

A New Experimental Model of Acute Muscle Pain in Humans Based on Short-wave Diathermy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03573219
• Other study ID #: IS001890
• Status: Completed
• Phase: N/A
• Start date: February 19, 2018
• Est. completion date: August 29, 2018

Study information

• Verified date: August 2018
• Source: National Council of Scientific and Technical Research, Argentina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the use of short-wave diathermy (SWD) as an novel experimental model to induce transient and intensity-controlled muscle pain by heating muscle tissue.

Description:

Application of short-wave diathermy All researchers, students and postdocs involved in experimental application of SWD will be properly trained by the Non-Ionizing Radiation Research Group of the National University of Entre Ríos. The application of SWD will be carried out by a CEC M-8 short-wave thermotherapy unit (CEC Electrónica, Córdoba, Argentina). The device has capacitive applicators, that will be situated around the muscle to be irradiated on top of a cotton towel, in order to absorb perspiration and avoid undesired heating effects. Afterwards the emission mode (continuous or pulsed) will be selected, and application of SWD will start. The intensity of SWD will be gradually increased until the volunteer perceives a warm sensation, and once familiarized with this perception, the intensity will be increased until a sensation of constant but tolerable pain is evoked. This sensation will be maintained throughout the duration of the SWD application, estimated in approximately 10 minutes. In case the volunteer feels excessive discomfort or does not adequately tolerate the application of SWD, the device will be turned off immediately and the experimental session will finish.

Experimental pain model assessment

• Model direct effects: maximum and average pain ratings will be assessed through a Visual Analog Scale (VAS). The VAS ranges from 0 to 10, where 0 represents no perception, 3 represents the pain threshold (i.e. the minimum irradiation intensity that elicits pain) and 10 represents the tolerance threshold (i.e. the irradiation intensity that elicits an intolerable pain sensation). Duration of pain will also be recorded, in case the experiment has to be interrupted before SWD application is completed and to assess potential cases in which pain outlasts SWD application. Furthermore, delivered RF power will be measured using a Bird 43 RF wattmeter (Bird Technologies, OH, USA).

• Pressure stimulation: pressure stimulation will be applied through a Somedic algometer (Somedic SenseLab AB, Sweden), directly over the muscle being examined, using a 1 cm2 round tip. Pressure will be gradually increased from 0 kPA until a maximum of 1000 kPa at a rate of approximately 30 kPa/s. Pressure pain threshold (PPT) will be defined as the force at which the pressure sensation becomes painful. Pressure tolerance threshold (PTT) will be defined as the force at which pressure sensation becomes intolerable. If any of the threshold are not reached until the pressure is increased to 1000 kPa, the this value will be considered as the corresponding threshold.

• Pinprick and tactile stimulation: pinprick stimuli will be applied on the skin over the muscle being examined using a set of pinprick stimulators, consisting on a needle with a 0.25 mm tip linked to calibrated weights, ranging from 1 g to 50 g, in order to apply forces between 8 and 500 mN approximately. Dynamic tactile stimulation will be applied by stroking a cotton tip over the skin. Pinprick sensitivity (PS) and dynamic tactile sensitivity (DTS) will be quantified using the VAS described above.

• Electrical stimulation: electrical stimuli will be applied to the skin over the muscle being examined using a concentric electrode, in which the cathode is made of 16 stainless steel blunt pins with 0.2 mm diameter tips and 1 mm length, and the anode is a concentric stainless steel ring of 20 mm diameter. The electrical stimulus will consist on a rectangular pulse of 1 ms duration, generated by a Biopac STMISOLA constant-current electrical stimulator (Biopac Systems Inc., California, USA). Stimulation intensity will be increased from 1 mA in steps of 0.5 mA until a pain sensation is evoked. This intensity will be defined as the electrical pain threshold (EPT). Once the EPT is determined, repeated stimulation will be applied referenced to this intensity in order to record somatosensory evoked potentials (SEPs) through surface electroencephalography (EEG).

• Motor responses: motor responses will be recorded from upper and lower limbs. For the upper limb, two sets of experimental motor tasks are planned, and the overall aim is to measure changes in precision in the execution of the motor tasks due to pain. The first one will be a simple task, basically consisting on the use of a joystick to move a cursor to a two-dimensional moving target displayed in a computer screen. Specific details of the implementation of the optimal setup for this motor task and the required software will be provided by collaborators from the Physiology of Action Lab at Universidad de Buenos Aires. The second motor task will involve more complex movements and haptic feedback, provided by a Phantom Omni haptic device (SensAble Technologies, Inc., Massachusetts, USA). The haptic device can provide controlled levels of force feedback (up to 3.3 N) and a precise mapping of the trajectories employed in the motor task in three dimensions (resolution: 0.055 mm). Specific details of the implementation of the optimal setup for this motor task and the required software will be provided by collaborators from the Robotics Research Group at National University of Entre Ríos. For the lower limb, the motor task will consist on a balance task performed over high-resolution pressure sensing platform that will be able to record differences in weight loading between left and right leg and variations in the center of pressure (CoP). The platform is a recent technological development from the Electronic Prototyping and 3D Printing Lab at the Faculty of Engineering of National University of Entre Ríos, and it has a sensing area of 430 x 320 mm, with a resolution of 4 pressure sensors per cm2 and a measurement range from 1 to 785 kPa.

• Brain responses: EEG will be recorded using a Neuroscan SynAmps amplifier (Compumedics Ltd., Victoria, Australia) during the planning and execution of motor tasks, in order to evaluate changes in movement-related cortical potentials (MRCP) in relation to SWD-induced pain (Jochumsen et al. 2015). Additionally, resting-state EEG will be recorded before, during and after SWD application, in order to assess potential changes in functional connectivity (FC) (Mayhew et al. 2013). FC analysis will be performed by collaborators from CNAP at Aalborg University.

Sample size considerations

The experimental design is an interventional, pre-post study design (Thiese 2014), in which each participant acts as his own control. Sample size calculation will be performed taking into account the expected effect size that the model will have on the primary outcome (PPT). Several experiments have shown that PPT in the wrist extensor/flexor muscles (e.g. extensor carpi radialis longus) is around 350 ± 150 kPa (mean ± standard deviation), whereas PPT for the ankle dorsiflexor muscles (e.g. tibialis anterior) is around 600 ± 250 kPa (Fischer 1987; Delfa de la Morena et al. 2013). On the other hand, there is no existing information on the expected size of the difference in PPT due to the application of SWD, so this value will be approximated taking into account reference values of differences in PPT generated by other experimental models of pain, such as the injection of hypertonic saline solution or delayed onset muscle soreness. In these cases, PPT is usually reduced between 10 and 30% during the effects of the model, so an average of 20% difference will be considered in order to calculate the sample size for these experiments. Considering a probability of making a type I error (α) of 5%, a statistical power (1 - β) of 80%, and an estimated correlation between measures of 0.8, the sample size required to detect the aforementioned difference is 16 volunteers for the experiment in the upper limb and 17 volunteers for the experiment in the lower limb. In order to account for an unexpectedly larger variation, 20 subjects are expected to be recruited for each experiment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 29, 2018
• Est. primary completion date: August 29, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Understanding of the content and scope of the experiment, and compliance with the experiment's instructions.

• To have signed the informed consent.

Exclusion Criteria:

• Pregnancy.

• Previous history of neurological or musculoskeletal disorders or chronic pain.

• Previous history of addictive behavior, defined as abuse of alcohol, cannabis, opioids or other drugs.

• Previous history of thermosensitivity disorders.

• Previous history of mental illness.

• Presence of fever, tuberculosis, tumors, infectious processes, or acute inflammatory processes.

• Implantation of peacemaker or metallic prosthesis.

• Use of analgesics within 24 h prior to the experiment.

Related Conditions & MeSH terms

• Musculoskeletal Injury
• Musculoskeletal Pain
• Myalgia

Intervention

Radiation:
• Short-wave diathermy
The application of SWD will be carried out by a CEC M-8 short-wave thermotherapy unit. The device has capacitive applicators, that will be situated around the muscle to be irradiated on top of a cotton towel, in order to absorb perspiration and avoid undesired heating effects. Afterwards the emission mode (continuous or pulsed) will be selected, and application of SWD will start. The intensity of SWD will be gradually increased until the volunteer perceives a warm sensation, and once familiarized with this perception, the intensity will be increased until a sensation of constant but tolerable pain is evoked. This sensation will be maintained throughout the duration of the SWD application, estimated in approximately 10 minutes.

Locations

Country	Name	City	State
Argentina	Facultad de Ingeniería - Universidad Nacional de Entre Ríos (Argentina)	Oro Verde	Entre Ríos

Sponsors (1)

Lead Sponsor	Collaborator
National Council of Scientific and Technical Research, Argentina

Country where clinical trial is conducted

Argentina, 

References & Publications (4)

Goats GC. Continuous short-wave (radio-frequency) diathermy. Br J Sports Med. 1989 Jun;23(2):123-7. Review. — View Citation

Graven-Nielsen T. Fundamentals of muscle pain, referred pain, and deep tissue hyperalgesia. Scand J Rheumatol Suppl. 2006;122:1-43. Review. — View Citation

Neziri AY, Scaramozzino P, Andersen OK, Dickenson AH, Arendt-Nielsen L, Curatolo M. Reference values of mechanical and thermal pain tests in a pain-free population. Eur J Pain. 2011 Apr;15(4):376-83. doi: 10.1016/j.ejpain.2010.08.011. Epub 2010 Oct 6. — View Citation

Vuilleumier PH, Biurrun Manresa JA, Ghamri Y, Mlekusch S, Siegenthaler A, Arendt-Nielsen L, Curatolo M. Reliability of Quantitative Sensory Tests in a Low Back Pain Population. Reg Anesth Pain Med. 2015 Nov-Dec;40(6):665-73. doi: 10.1097/AAP.0000000000000289. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pressure pain threshold (PPT)	Change in the pressure pain threshold (kPa) recorded after the induced of muscle pain using SWD on the established time point records.	0 to 1 hour
Secondary	Assessment of changes in pain intensity in direct relation to the experimental model	Maximum and average pain ratings (0 to 100 score).	0 to 1 hour
Secondary	Assessment of changes in pain time course in direct relation to the experimental model	Duration of pain (seconds)	0 to 1 hour
Secondary	Assessment of changes in functional connectivity in direct relation to the experimental model	Changes in functional connectivity (FC), assessed through surface electroencephalography (EEG).	0 to 1 hour
Secondary	Assessment of changes in Pinprick sensitivity	Pinprick sensitivity (PS) (0 to 100 score).	0 to 1 hour
Secondary	Assessment of changes in Dynamic tactile sensitivity	Dynamic tactile sensitivity (DTS) (0 to 100 score).	0 to 1 hour
Secondary	Assessment of changes in Electrical pain threshold	Electrical pain threshold (EPT) (mA).	0 to 1 hour
Secondary	Assessment of changes in Somatosensory evoked potentials	Somatosensory evoked potentials in response to electrical stimuli (SEP), assessed through EEG. (mV)	0 to 1 hour
Secondary	Assessment of changes in Movement-related cortical potentials	Change in Movement-related cortical potentials (MRCP), assessed through EEG.	0 to 1 hour
Secondary	Assessment of changes in motor responses for upper limb	Change in precision during motor execution (percentage)	0 to 1 hour
Secondary	Assessment of changes in motor responses for lower limb	Change in balance (Centre of pressure)	0 to 1 hour
Secondary	Assessment of changes in weight loading	Measured in Kg	0 to 1 hour