Pelvic pain (PP) is associated with more than 20 different, clinically identified, maladies, such as Urinary Tract Infection (UTI), Menstrual Cramps (MC), Endometriosis (EM), Overactive Bladder (OAB) and Interstitial cystitis/Painful bladder syndrome (IC/PBS). These painful and debilitating conditions often have a dramatic negative impact on the quality of life (QOL) of millions of PP sufferers, from decreased work productivity and school performance, to declined sexual life and happiness. PP has been also associated with increased abuse of opioids and psycho-pharmaceuticals, ultimately leading to death by overdose and suicides. In addition to the burden to patients and their family, the economic direct and indirect PP cost is a significant fraction (>20%) of the 635B$ linked to chronic pain in US. Globally, pelvic pain affects one in five women and one in twelve men. Although treatments, including neural stimulation, are available, they are costly and lose effectiveness over time in >30% of patients. Patients with current untreatable chronic PP require a novel treatment approach that can relieve them from their debilitating symptoms. Significant relief of pain and reduced urination frequency has been recently associated with thermal modulation of pelvic floor. H3Pelvic has successfully developed a Contrast Applied Therapy (CAT) system modulating rapidly and comfortably temperature (cold/warm) via a water- circulating perineal membrane in a soft seat. When a properly sized vaginal or rectal probe with superior thermal conductivity is combined with the CAT system, the pain relief can be remarkable: an initial cohort of patients with refractory IC, unresponsive to drugs or neural stimulation, with a daily 45min vaginal cooling, resumed normal undertakings, restarted school, work and sexual activity, leading to an overall happier and productive life. We propose to optimize a probe design to maximize targeted delivery of thermal modulation using heatpipe technology, including real-time temperature tracking by passive microwave radiometry. RICAT (Radiometry Integrated CAT) will use probe-integrated smart radiometry to monitor deep tissue temperature. By leveraging machine learning, a minimal set of sensors shall accurately reconstruct temperature in the target region and maximize pain reduction. The Specific Aims for this first Phase are: 1) Optimally integrate radiometric sensors and smart planning/control software in a RICAT prototype; 2) Compare radiometric profiles with invasive needle sensors and perform histology in ex-vivo tissues and 7 pigs undergoing vaginal or rectal cooling/warming cycle. The goal of this Phase I is to integrate radiometric sensing into the thermal probe and test the probes ability to deliver consistent cooling and heating in the pelvic region in pre-clinical settings using healthy pigs. The data collected will allow us to move to Phase II, which will include a human trial in refractory IC patients. We expect that the animal study will show that RICAT optimally delivers pain-relieving thermal modulation to the pelvic region(s) effectively and reliably. Successful Phase I completion will pave the path towards clinical translational of a safe and effective pain-relieving technology to millions of patients suffering from debilitating pelvic pain.
Public Health Relevance Statement: PUBLIC HEALTH AND RELEVANCE STATEMENT We propose to combine multi-frequency radiometry with thermal modulation (cold/hot) of the pelvic region via a vaginal or rectal heatpipe-enhanced thermal wicking probe to reduce dramatically the pain associated with refractory interstitial cystitis and other chronic pelvic pain conditions. The novel, affordable and effective intraluminal therapeutic system will improve the quality of life, allow return to normalcy and support the personalized hospital-at-home care, ultimately benefiting millions of low-resource patients in US and worldwide.
Project Terms: Affect; Pain Control; Pain Therapy; pain treatment; Pain management; Analgesic Agents; Analgesic Drugs; Analgesic Preparation; Anodynes; Antinociceptive Agents; Antinociceptive Drugs; pain killer; pain medication; pain reliever; painkiller; Analgesics; Anesthesia; Anesthesia procedures; Animals; Anti-Inflammatories; Anti-inflammatory; Antiinflammatories; Antiinflammatory Agents; antiinflammatory; Anti-Inflammatory Agents; Antidepressant Agent; Antidepressant Drugs; Antidepressants; anti-depressant agent; anti-depressant drugs; anti-depressants; anti-depressive agents; Antidepressive Agents; Bladder; Bladder Urinary System; urinary bladder; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Economics; economic; endometriosis; Energy Transfer; Family; Feedback; Food; Goals; Happiness; positive attitude; Heating; Histology; Hospitals; Human; Modern Man; men; Menthol; microwave electromagnetic radiation; Microwave Electromagnetic; Microwaves; microwave radiation; Mucous Membrane; Mucosa; Mucosal Tissue; Muscle Cramp; Cramp; Muscular Cramp; Needles; Afferent Neurons; Sensory Neurons; Nociceptors; nociceptive neurons; pain-sensing neurons; pain-sensing sensory neurons; pain-sensing somatosensory neurons; opioid abuse; opiate abuse; opiate drug abuse; opioid drug abuse; Pain; Painful; Patients; Pelvic Pain; Pelvis; Pelvic; Pelvic Region; Personal Satisfaction; well-being; wellbeing; Productivity; Psychotropic Drugs; Psychoactive Agents; Psychoactive Compound; Psychoactive Drugs; Psychopharmaceuticals; Public Health; Quality of life; QOL; Radiometry; Radiation Dosimetry; radioassay; Sensory Receptors; Neural Receptors; Neuroreceptors; Rectum; Resources; Research Resources; Schools; Sex Behavior; Sexual Activity; Sexual Behavior; sex activity; sexual activities; Computer software; Software; Spasm; Hyperkinesia; Hyperkinesis; Hyperkinetic Movements; Muscle Spasm; Muscular Spasm; Suicide; fatal attempt; fatal suicide; intent to die; suicides; Family suidae; Pigs; Suidae; Swine; porcine; suid; Tampons; Technology; Temperature; Testing; Thermal Conductivity; Time; Tissues; Body Tissues; Increased frequency of micturition; Urinary Frequency; Urinary tract infection; Urinary tract infectious disease; urinary infection; Urination; micturition; Vagina; Vaginal; Water; Hydrogen Oxide; Woman; Work; Eucalyptol; 1,8-cineol; 1,8-cineole; 1,8-epoxy-p-menthane; cineole; Muscle strain; Urgency to pass urine; Urgent desire to urinate; urinary urgency; urination urgency; micturition urgency; Chronic Prostatitis; Family member; chronic pain; Thermometry; sensor; improved; Acute Pain; Home Care; patient homecare; patient home care; rectal; Peripheral; Area; Acute; Clinical; Refractory; Phase; Pelvic Floor; Pelvic floor structure; Link; Opiates; Opioid; bladder pain syndrome; painful bladder syndrome; Interstitial Cystitis; Therapeutic; Absence of pain sensation; Absence of sensibility to pain; Feels no pain; No sensitivity to pain; analgesia; Machine Learning; machine based learning; Life; TRP channel; Transient receptor potential channel; Frequencies; Visceral; System; Membrane; membrane structure; Performance; receptor; Receptor Protein; success; drinking water; cohort; treatment planning; novel; Topical application; Topical Drug Administration; administer topically; apply topically; deliver topically; topical administration; topical delivery; topical drug application; topical treatment; topically administered; topically applied; topically delivered; topically treated; treat topically; Devices; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; portability; Overactive Bladder; Normalcy; Normalities; normality; A vaginae; A. vaginae; Atopobium vaginae; Effectiveness; Data; Validation; validations; Monitor; socioeconomics; socio-economic; socio-economically; socioeconomically; Pathway interactions; pathway; pre-clinical; preclinical; chronic pelvic pain; chronic pelvic pain syndrome; cost; designing; design; Outcome; site targeted delivery; targeted delivery; neural stimulation; somatosensory; patient centered; patient oriented; prototype; effective treatment; effective therapy; overdose fatalities; overdose death; debilitating symptom; disabling symptom; clinically translatable; clinical translation; reduce pain; pain reduction; relieve pain; pain relief; optimal therapies; optimal treatments; functional electrostimulation; functional electrical stimulation; skin burn
