1. Pathway
System Overview

2. Pain & Sensory Evaluation System
PATHWAY
Pain & Sensory Evaluation System
A computerized thermal stimulator designed for advanced neurological & pain research
ATS – Advanced thermal Stimulator, CHEPS – Contact-heat evoked potential simulation
ATS – ADVANCED THERMAL STIMULATOR
CHEPS – Contact-heat evoked potential stimulation

3. PATHWAY Hardware capabilities:
Accurate temperature control loop (200 Hz)
Self test and built-in test (BIT)
In & out event synchronization
Computerized Visual Analog Scale (COVAS)
Manual trigger
Response unit
Emergency safety shut down
Upgradeable configuration
Out synchronization - Outside order for the system to act – from an external program like Matlab
In synchronization - TTL signal that the system sends to the fMRI / EEG machine
Manual trigger – specific keyboard buttons (that the used defines for himself) to mark specific events

4. PATHWAY Software capabilities:
Support for Windows- up to10 (32 & 64 bit).
License protected
Authorization levels
Patient, program and test results management
Easy database management
Demo mode is open to all licenses
Simple Installation and upgrade procedures

5. PATHWAY Advantages
Large thermode enables more nociceptors activation, thus evoking a stronger brain response
Pre determined stimulation protocol for selectively activating the A-δ and C fibers (responsible for pain sensation)
Superior safety mechanisms
Quick set-up and test initiation
Easy hardware & software upgrading
Temperature measurement on the thermode’s active area during the test, to assure constant accuracy (±0.3ᵒC)
fMRI Conditional PATHWAY is available in various configurations
A-δ – cold detection, C fibers – warm detection

6. PATHWAY model CHEPS Unique Features: Heating rate of up to 70°C/sec.
32°C to 55°C in 300 ms
Cooling rate of down to 40°C/sec (from 55°C to 32°C – baseline)
Cold sensation evoked potentials cooling rate of 15°C/Sec from 32°C to 25°C
27 mm2 diameter thermode for stronger cerebral response
27 mm2 = Diameter = 5mm – smallest - allowing strongest and most concentrated stimuli

7. PATHWAY model CHEPS Applications:
Objective measurement of pain perception
Pain Evoked Potentials: Selective A-δ and C fibers stimulation
Heat Pain & Warm Sensation
Cold Sensation Evoked Potentials
Temporal Summation (Windup)
Sensory function investigation
Flexible test algorithms
Windup
(sensation of pain)
Windup (temporal summation) -  occurs when a high frequency of action potentials in the neuron elicits post-synaptic potentials that summate with each other.
Stimuli = action potential. A lot of stimuli = a lot of “firing” of action potentials  creating a summation of all the potentials into a hot ball of pain.
Inhibition - ‘diffuse noxious inhibitory controls’ (DNIC) which explains the effectiveness of the commonly-known ‘pain-inhibits-pain’.
The term ‘‘conditioned pain modulation” (CPM) has been introduced to describe this psychophysical phenomenon, that allows pain inhibition of a painful stimulus by a second painful stimulus delivered at a different body location.
The brain circuitry responsible for CPM remains unknown.

8. PATHWAY model CHEPS Accessories:
Computerized Visual Analog Scale (CoVAS)
Parallel Control S/W
fMRI Thermode
fMRI Filter
PATHWAY coolant cleaning Kit

9. PATHWAY model ATS Unique features :
Extreme hot pain stimulation of up to 54°C
Extreme cold pain stimulation of down to -10°C
Thermodes of two sizes (mm): 30x30, 16x16
ATS – Advanced thermal stimuli (like TSA-II but a broader temperature range)
Thermode 30x30mm
Thermode 16x16mm

10. PATHWAY model ATS Applications:
Rapid and reliable measurement of Thermal Sensation & Pain thresholds.
Cold Pain studies
Variety of test protocols
Flexible text algorithms

11. PATHWAY model ATS Patient response unit 16x16mm thermode
Accessories:
Patient response unit
16x16mm thermode
Computerized Visual Analog Scale (CoVAS)
fMRI thermodes
fMRI filter
Parallel Control S/W
PATHWAY coolant cleaning kit

12. fMRI PATHWAY
Both CHEPS and ATS models can be configured for use in a magnetic environment
When using fMRI PATHWAY (ATS / CHEPS) researchers can administer noxious and innocuous stimuli and obtain the brain’s response
In PATHWAY model CHEPS: Stimuli can be synchronized with an fMRI compatible EEG system for multi-modality study of selective nerve fibers activation and cortical response
noxious stimuli - intense and unpleasant stimuli, possibly damaging (pinching, pricking, exposure to acid, high or low temperatures, etc. ).
Innocuous – NOT a painful or damaging stimuli, like brushing at 2 Hz, or touching with a cotton swab. Can be painful to people with allodynia

13. fMRI PATHWAY Accessories: 10m long CHEPS Thermode
10m long ATS Thermode
fMRI filter
fMRI CoVAS
10m long panic button
10m long Patient Response Unit

14. The Pain Market
Historically, pain clinics were an integral part of either the Anesthesiology or the Neurology departments
Today, pain is considered an independent discipline, and as such the number of pain clinics is rapidly growing, with almost every big hospital having its own pain clinic
Misdiagnosis and under-treatment of pain conditions are proven to be harmful, reinforcing the need for better pain management

15. Growing Epidemic of Pain
Chronic pain is considered the most costly health problem in North America, with annual cost of chronic pain in the U.S, is estimated to be $100B per year and over $300B costs due to loss of productivity
Chronic pain is the number one cause of long-term disability in the United States, with over 100M patients in the US, and 1.5B patients worldwide
According to a European Journal of pain, chronic pain affects over 19% of the European population, with undetermined cause for the pain in 80% of cases, and 85% of pain patients lack a specific diagnosis
The worldwide neuropathic pain market is expected to increase from $5.5 billion in 2017 to $ 8.3 billion by 2024
Chronic pain is considered the most costly health problem in North America – from 2014
$300B costs due to loss of productivity – from 2014

16. The fMRI Market
fMRI has became a fundamental research tool around the globe
Constantly growing number of fMRI-related scientific articles in with Medoc’s devices reinforces the company’s important role in pain research field
Since 2000, Medoc has sold a over 230 fMRI compatible systems worldwide

17. fMRI Users Selected fMRI user list: NIH (National Institute of Health)
Massachusetts General Hospital
University of Toronto
University of Munich
National Yang-Ming University, Taipei

18. The Pharmaceutical Trial Market
Medoc products are used by world-known pharmaceutical companies conducting clinical trials – such as Pfizer, GlaxoSmithKline, Merck, AstraZeneca, Dainippon, Unilever, Quintiles, Pro-Derm, Sigma Tau, and others
Effectiveness and safety of prospective compounds for neurological, diabetic, and pain conditions can be established by examining small-fiber functionality using Medoc’s systems

19. The Pharmaceutical Trial Market
Medoc’s systems can be used for a variety of applications in clinical trials
Phenotyping patients based on underlying pain mechanisms – Allowing to identify and recruit only patients who are expected to benefit from the treatment
Secondary outcome measures – quantitative and standardized secondary analgesic efficacy measures, to assess the analgesic efficacy and support extended labeling of the investigated compound
Safety outcome measures – monitor small fiber function and assure no ill effects are caused by the investigated compound
Analgesic compound have a very low success rate in clinical trials, it usually helps 10-15% of the tested patients.
So lets say we have 100 patients with diabetic neuropathy, of whom the new drug helps only 15 people.
But in many cases this is because the underlying mechanism of pain is different for patients with the same disorder, meaning the fibers are functioning badly due to different underlying reasons, and the drug effectively treats just one of the reasons.
So it’s now recommended to do Phenotyping – which is dividing patients to subgroups based their underling pain mechanisms, so that we could identify and recruit only patients who are expected to benefit from the treatment. In our example, in stead of the original 100 patients we will take only 20. so the orginal 15 people who had a good response to the drug become a 75% success rate

20. Selected Pharmaceutical Companies
Medoc’s systems have also been selected for use in pre-clinical and multi-center pharmaceutical trials of companies such as:
Pfizer
GlaxoSmithKline
Merck
AstraZeneca
Sigma Tau
Dainippon
Unilever

21. Thank you!