Clinical trial NCT03855930: Phantom Limb Pain Triggered by Micturition
Official title: Phantom Limb Pain Triggered by Micturition, An Functional Magnetic Resonance Imaging (FMRI) Study in Lower Limb Amputees
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Phantom Limb Pain
Lead sponsor: Loewenstein Hospital
Sponsor class: OTHER
Collaborators: name: Tel Aviv University
First posted: 2019-02-27
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. 10 Patients with chronic post amputation micturition induced PLP.All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
2. 10 Patients with chronic post amputation with PLP and without post amputation micturition induced PLP All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
3. 10 healthy volunteers

Brief summary: Phantom Limb Pain ( PLP) is pain that is perceived and referred to a region of the body that is no longer present. in most patients, severity and frequency of phantom pain attacks gradually decrease over several weeks to 2 years following amputation, however in 5-10% significant pain remains a serious problem.

It has been hypothesized, that deprivation of various inputs from the limbs to the brain cause an abnormal neuro-signature to be produced generating cortical maladaptive neuroplasticity and reorganization. Areas representing the amputated body part are taken over by neighboring representational zones in both the somatosensory and motor cortex generating pain in absence of stimuli.

A seminal paper published by Lotze et al "Phantom movements and pain: a functional magnetic resonance imaging (fMRI) study in upper limb amputees. - participants had to pucker their lips at a metronome-paced speed while functional magnetic resonance images were taken. Only in amputees with phantom-limb pain did a shift of the mouth representation into the hand representation occur; those without pain and the healthy control do not display a similar shift.

Scarce reports have been made on a similar phenomenon- micturition induced lower limb phantom pain.

We speculate that a similar maladaptive central nerve system (CNS) plasticity in which this genital representation would invade cortical areas with somatotopic affiliation to the lower extremity could be implicated in the pathophysiology of this phenomenon.

Detailed description: The present study was there for devised to examine this hypothesis utilizing fMRI imaging of temporo-spatial cortical activation during micturition and pain generation.

We hypothesis that in amputees with phantom-limb pain a shift of the genital representation into the leg representation will occur; and will be demonstrated as an uni-hemispheral activity on fMRI during micturition and pain suggesting maladaptive CNS plasticity. Moreover, we speculate that healthy volunteers will not display a similar shift.

During the study, standard motor and sensory paradigms will be performed to establish anatomical and functional patterns in the non-painful state. The patient will then be asked to urinate (to an external collecting tube system).

All anatomical data will be examined by a certified clinical imaging specialist to exclude concomitant brain pathology.

Study population -

1. 10 Patients with chronic post amputation micturition induced PLP.All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
2. 10 Patients with chronic post amputation with PLP and without post amputation micturition induced PLP All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
3. 10 healthy volunteers

FMRI data analysis signifying, statistically significant uni-spatial voxel activity during micturition, in the study group

Eligibility criteria: Inclusion Criteria:

* 9 months or more post amputation, no anatomical stump pathology
* Ambulatory and to comply with study protocol
* Suffering from significant pain (VAS\>??). pain level has plateaued for at lest 2 months prior to enrolment.
* Pain is perceived to be located in the missing limb
* Pain level is brought up or increases (by at least 3 VAS points) by micturition.
* Maneuvers causing abdominal pressure elevation do not generate similar symptoms.
* Subject received an explanation about the nature of the study and agrees to provide written informed consent
* Subject is capable and willing to follow all study-related procedures

Exclusion Criteria:

* Any condition inhibiting MRI study (e.g.Pacemakers or other implantable neurostimulators, ....)
* Subject has any condition, which precludes compliance with study instructions.
* Subject suffers from life threatening conditions
* Anatomical limitations that would prevent successful FMRI study
* Other medical conditions precluding FMRI study - e.g., claustrophobia
* Women gender- due to problematic usage of external urinating device during fMRI study

Primary outcomes:
measure: FMRI data analysis
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Ra'anana
country: Israel
facility: Loewenstein Rehabilitation Center
city: Raanana
country: Israel
facility: Loewenstein Rehabilitation Center
Study officials:
affiliation: Loewenstein Rehabilitation Hospital
name: Motti Ratmansky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Michels L, Blok BF, Gregorini F, Kurz M, Schurch B, Kessler TM, Kollias S, Mehnert U. Supraspinal Control of Urine Storage and Micturition in Men--An fMRI Study. Cereb Cortex. 2015 Oct;25(10):3369-80. doi: 10.1093/cercor/bhu140. Epub 2014 Jun 26.
citation: Flor H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neurol. 2002 Jul;1(3):182-9. doi: 10.1016/s1474-4422(02)00074-1.
citation: Shy M, Fung S, Boone TB, Karmonik C, Fletcher SG, Khavari R. Functional magnetic resonance imaging during urodynamic testing identifies brain structures initiating micturition. J Urol. 2014 Oct;192(4):1149-54. doi: 10.1016/j.juro.2014.04.090. Epub 2014 Apr 21.