Pain
Conditions
Brief summary
This study is a methodology study designed to discover whether a brain imaging technology is a better way of compare the relative sensitivities of fMRI and subjective psychometric assessments of pain to multiple doses of pregabalin and tramadol SR in a cross-over clinical study design.
Interventions
DRUGPlacebo
BID
DRUGPregabalin
Dose 75 mg titrated to 150 mg, bid
DRUGTramadol SR
Dose 50mg titrated to 200 mg, bid
Sponsors
University of Oxford
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of neuropathic pain associated with brush allodynia in specific dermatomes. * Brush allodynia score of ≥4 and calculated average pain score of ≥3 on an 11-point numerical rating scale by the completion of down-titration of existing medications. * Right-handed
Exclusion criteria
* Subjects with trigeminal neuralgia, central pain (due to cerebrovascular lesions, multiple sclerosis and/or traumatic spinal cord injuries including spinal surgery). * Phantom limb pain, painful diabetic neuropathy. * Subjects with any other co-existing pain which he/she or a qualified pain physician cannot differentiate from NeP of peripheral origin. * Subjects with diabetes mellitus and with an HbA1C value of \>10% upon measurement at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Voxel-wise Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals Across the Whole Brain | Day 8, 22, 36 | BOLD brain activation signals in whole brain was assessed using Contrast Parameter Estimates (COPE) images in response to dynamic mechanical allodynia of the affected side (DMAa), dynamic mechanical allodynia of the control side (DMAc), thermal pain (TH) and checkerboard visual stimuli (VIS). |
| Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | Day 8, 22, 36 | BOLD brain activation signals in pre-defined region of interest(ROI):anterior cingulate cortex(ACC);left,right anterior cortex(\[AIC\_L \],\[AIC\_R\]);left,right mid-insular cortex(\[MIC\_L\],\[MIC\_R\]);left,right posterior insular cortex(\[PIC\_L\],\[PIC\_R\]);left,right amygdala(\[Amyg\_L\],\[Amyg\_R\]);primary,secondary somatosensory cortex(\[S1\],\[S2\]);sensory part of thalamus(SensTHAL);midbrain reticular formation(MRF);nucleus cuneiformis(NucCun);periaqueductal gray(PAG). Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only. In voxel BOLD analysis,signal change is unit less measure but approximated to percent signal change by grand scaling(effects divided by 10000 to get percent signal change). |
| Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | Day 8, 22, 36 | BOLD brain activation signals in pre-defined ROI. ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG. Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only. In voxel BOLD analysis, signal change is unit less measure but is approximated to percent signal change here by grand scaling (dividing effects by 10000 to get percent signal change). |
| Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | Day 8, 22, 36 | BOLD brain activation signals in pre-defined ROI. ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG. Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only. In voxel BOLD analysis, signal change is unit less measure but is approximated to percent signal change here by grand scaling (dividing effects by 10000 to get percent signal change). |
| Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Visual Stimulation (VIS) | Day 8, 22, 36 | BOLD brain activation signals in pre-defined ROI in response to checkerboard visual stimuli (flashing at 2 Hz). ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG. Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only. |
| Arterial Spin Labelling (ASL) Using fMRI of Brain Activation Signals Across the Whole Brain and in Defined Brain Regions | Day 8, 22, 36 | Continuous ASL sequence fMRI imaging modality assessing brain activation signals across the whole brain and in defined ROI to assess effects of evoked pain along with changes in regional cerebral blood flow (rCBF). ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Present Pain Intensity Score (PPIS) | Day 8, 22, 36 | Participants answered: Please rate your pain from 0-10 that best describes the intensity of pain right now. PPIS assessed on 0-10 numeric rating scale (NRS), 0 (no pain) to 10 (worst possible pain). |
| 36-Item Short-Form Health Survey (SF-36) | Day 8, 22, 36 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). |
| Doleur Neuropathic 4 (DN4) Score | Day -35 | DN4 questionnaire provides a simple diagnosis of Neuropathic pain (NeP) by asking for yes/no answers to 4 questions (10 sub questions in total). Each question was scored on a scale of 0 (No) and 1 (Yes). Total score was calculated as sum of the 10 individual questions. Total score range 0-10, higher score indicated more neuropathic pain. |
| Beck Depression Inventory (BDI) | Day 8, 22, 36 | BDI is a 21 item participant rated inventory evaluating depression symptoms, cognition, and physical symptoms of fatigue, weight loss, lack of interest in sex. Individual items are scored on a 4 point scale (0 to 3), with 0=none/absent and 3=most severe. Total score: 0 to 63; higher score indicate more depression. |
| State and Trait Anxiety Questionnaire | Day 8, 22, 36 | Self-report scale completed by the participant. Separate scales measure state (20 items) and trait (20 items) anxiety. The participant report how they feel right now at this moment for state anxiety and how they generally feel for trait anxiety. The state items are scored as: 1 (not at all), 2 (somewhat true), 3 (moderately true), 4 (very much so). The trait items are scored as: 1 (almost never), 2 (sometimes), 3 (often), 4 (almost always). Scores range from 20-80 for each scale. Higher scores indicate more impaired participants. |
| Pain Catastrophising Scale (PCS) | Day 8, 22, 36 | The PCS is a self-administered questionnaire with 13 items, each scored from 0 (not at all) to 4 (all the time) for extent to which participant catastrophizes postoperative pain. Total score is sum of scores for all questions (range: 0 to 52); Subscale scores: Rumination (sum of scores for 4 items; range: 0 to 16); Magnification (sum of scores for 3 items; range: 0 to 12); and Helplessness (sum of scores for 6 items; range: 0 to 24); higher scores indicate greater extent of pain catastrophizing. |
| Neuropathic Pain Symptom Inventory (NPSI) | Baseline (Day -7), Day 8, 22, 36 | NPSI: participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicate a greater intensity of pain. |
| Daily Pain Score | Day -35 through Day 36 | Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning using 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). The daily pain scores for an average of the last 7 days and an average of last 3 days were calculated. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all participants enrolled in the study. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 3 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 44.7 years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 17 | 14 / 17 | 11 / 18 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 18 |
Outcome results
Primary
Arterial Spin Labelling (ASL) Using fMRI of Brain Activation Signals Across the Whole Brain and in Defined Brain Regions
Continuous ASL sequence fMRI imaging modality assessing brain activation signals across the whole brain and in defined ROI to assess effects of evoked pain along with changes in regional cerebral blood flow (rCBF). ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG.
Time frame: Day 8, 22, 36
Population: Data was not analyzed since these methods were not technically robust enough to make any clear conclusions.
Primary
Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa)
BOLD brain activation signals in pre-defined region of interest(ROI):anterior cingulate cortex(ACC);left,right anterior cortex(\[AIC\_L \],\[AIC\_R\]);left,right mid-insular cortex(\[MIC\_L\],\[MIC\_R\]);left,right posterior insular cortex(\[PIC\_L\],\[PIC\_R\]);left,right amygdala(\[Amyg\_L\],\[Amyg\_R\]);primary,secondary somatosensory cortex(\[S1\],\[S2\]);sensory part of thalamus(SensTHAL);midbrain reticular formation(MRF);nucleus cuneiformis(NucCun);periaqueductal gray(PAG). Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only. In voxel BOLD analysis,signal change is unit less measure but approximated to percent signal change by grand scaling(effects divided by 10000 to get percent signal change).
Time frame: Day 8, 22, 36
Population: BOLD analysis set included all participants who completed all the 3 treatment periods of the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PIC_L | -6.8 percent signal change | Standard Error 5.2 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | NucCun | 1.1 percent signal change | Standard Error 5.5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | S1 | -28.5 percent signal change | Standard Error 20.5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PIC_R | -13.6 percent signal change | Standard Error 8.5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | AIC_R | 11.1 percent signal change | Standard Error 10 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | Amyg_R | -1.4 percent signal change | Standard Error 8.5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | Amyg_L | -5.7 percent signal change | Standard Error 10.2 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | ACC | -17.3 percent signal change | Standard Error 9.7 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MRF | 7.0 percent signal change | Standard Error 5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MIC_L | 3.8 percent signal change | Standard Error 8.4 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PAG | -3.8 percent signal change | Standard Error 7.9 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | SensTHAL | 8.0 percent signal change | Standard Error 5.4 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MIC_R | 8.6 percent signal change | Standard Error 8.4 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | AIC_L | 8.1 percent signal change | Standard Error 8.8 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | S2 | 2.5 percent signal change | Standard Error 10.8 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | SensTHAL | 16.5 percent signal change | Standard Error 5.4 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | ACC | 18.6 percent signal change | Standard Error 9.7 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | AIC_R | 21.9 percent signal change | Standard Error 10 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MIC_L | 23.4 percent signal change | Standard Error 8.4 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MIC_R | 13.4 percent signal change | Standard Error 8.4 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PIC_L | -5.8 percent signal change | Standard Error 5.2 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PIC_R | 2.9 percent signal change | Standard Error 8.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | Amyg_L | 5.5 percent signal change | Standard Error 10.2 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | Amyg_R | 20.3 percent signal change | Standard Error 8.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | S1 | -4.1 percent signal change | Standard Error 20.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | S2 | -3.2 percent signal change | Standard Error 10.8 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | AIC_L | 23.3 percent signal change | Standard Error 8.8 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MRF | 6.4 percent signal change | Standard Error 5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | NucCun | -0.9 percent signal change | Standard Error 5.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PAG | -15.3 percent signal change | Standard Error 7.9 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MIC_R | 18.3 percent signal change | Standard Error 8.4 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PAG | 2.5 percent signal change | Standard Error 7.9 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | S2 | 10.8 percent signal change | Standard Error 10.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MIC_L | 30.0 percent signal change | Standard Error 8.4 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | NucCun | 12.9 percent signal change | Standard Error 5.5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | SensTHAL | 9.6 percent signal change | Standard Error 5.4 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | AIC_R | 17.1 percent signal change | Standard Error 10 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | ACC | 7.4 percent signal change | Standard Error 9.7 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | Amyg_L | 8.5 percent signal change | Standard Error 10.2 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PIC_R | 6.5 percent signal change | Standard Error 8.5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | MRF | 11.7 percent signal change | Standard Error 5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | Amyg_R | 21.7 percent signal change | Standard Error 8.5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | PIC_L | -0.3 percent signal change | Standard Error 5.2 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | AIC_L | 30.8 percent signal change | Standard Error 8.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Affected Side (DMAa) | S1 | -2.9 percent signal change | Standard Error 20.5 |
Primary
Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc)
BOLD brain activation signals in pre-defined ROI. ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG. Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only. In voxel BOLD analysis, signal change is unit less measure but is approximated to percent signal change here by grand scaling (dividing effects by 10000 to get percent signal change).
Time frame: Day 8, 22, 36
Population: BOLD analysis set included all participants who completed all the 3 treatment periods of the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PIC_L | -14.9 percent signal change | Standard Error 6.9 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | AIC_R | -10.6 percent signal change | Standard Error 7.4 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | S2 | -0.4 percent signal change | Standard Error 8.3 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PIC_R | -17.2 percent signal change | Standard Error 9.4 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | AIC_L | -13.5 percent signal change | Standard Error 8 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | S1 | -31.6 percent signal change | Standard Error 16.2 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | Amyg_L | -14.3 percent signal change | Standard Error 7.3 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MRF | 1.5 percent signal change | Standard Error 4.6 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | Amyg_R | -10.3 percent signal change | Standard Error 9.7 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MIC_L | -7.6 percent signal change | Standard Error 8.4 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PAG | 1.6 percent signal change | Standard Error 7.8 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | ACC | -22.3 percent signal change | Standard Error 12 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MIC_R | -9.2 percent signal change | Standard Error 6.2 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | NucCun | 1.0 percent signal change | Standard Error 4.9 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | SensTHAL | 3.9 percent signal change | Standard Error 5.3 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | SensTHAL | -2.8 percent signal change | Standard Error 5.3 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | ACC | -3.7 percent signal change | Standard Error 12 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | AIC_L | 18.2 percent signal change | Standard Error 8 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | AIC_R | 10.3 percent signal change | Standard Error 7.4 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MIC_L | 9.7 percent signal change | Standard Error 8.4 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MIC_R | 2.8 percent signal change | Standard Error 6.2 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PIC_L | -8.1 percent signal change | Standard Error 6.9 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PIC_R | 2.4 percent signal change | Standard Error 9.4 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | Amyg_L | 1.5 percent signal change | Standard Error 7.3 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | Amyg_R | 2.0 percent signal change | Standard Error 9.7 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | S1 | -4.5 percent signal change | Standard Error 16.2 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | S2 | 9.6 percent signal change | Standard Error 8.3 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MRF | -6.6 percent signal change | Standard Error 4.6 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | NucCun | -8.2 percent signal change | Standard Error 4.9 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PAG | -12.0 percent signal change | Standard Error 7.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PIC_L | 0.8 percent signal change | Standard Error 6.9 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | NucCun | -1.8 percent signal change | Standard Error 4.9 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | S2 | 13.5 percent signal change | Standard Error 8.3 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MIC_R | 0.7 percent signal change | Standard Error 6.2 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MIC_L | 9.0 percent signal change | Standard Error 8.4 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | SensTHAL | 6.7 percent signal change | Standard Error 5.3 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | AIC_R | 20.2 percent signal change | Standard Error 7.4 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | ACC | 0.2 percent signal change | Standard Error 12 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | MRF | -1.7 percent signal change | Standard Error 4.6 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | Amyg_L | -3.4 percent signal change | Standard Error 7.3 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | AIC_L | 20.2 percent signal change | Standard Error 8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | Amyg_R | -3.8 percent signal change | Standard Error 9.7 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PIC_R | 6.3 percent signal change | Standard Error 9.4 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | PAG | -5.0 percent signal change | Standard Error 7.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Dynamic Mechanical Allodynia of the Control Side (DMAc) | S1 | 14.6 percent signal change | Standard Error 16.2 |
Primary
Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH)
BOLD brain activation signals in pre-defined ROI. ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG. Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only. In voxel BOLD analysis, signal change is unit less measure but is approximated to percent signal change here by grand scaling (dividing effects by 10000 to get percent signal change).
Time frame: Day 8, 22, 36
Population: BOLD analysis set included all participants who completed all the 3 treatment periods of the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PIC_L | 31.2 percent signal change | Standard Error 16 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | AIC_R | 121.7 percent signal change | Standard Error 20.7 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | S2 | 73.6 percent signal change | Standard Error 21.2 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PIC_R | 75.3 percent signal change | Standard Error 20.1 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | AIC_L | 92.1 percent signal change | Standard Error 21.9 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | S1 | -49.0 percent signal change | Standard Error 30.2 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | Amyg_L | 29.7 percent signal change | Standard Error 16.5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MRF | 34.3 percent signal change | Standard Error 14.7 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | Amyg_R | 77.5 percent signal change | Standard Error 22.5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MIC_L | 93.4 percent signal change | Standard Error 19.6 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PAG | 63.3 percent signal change | Standard Error 15.9 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | ACC | 102.2 percent signal change | Standard Error 25.9 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MIC_R | 106.6 percent signal change | Standard Error 17.3 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | NucCun | 38.7 percent signal change | Standard Error 11.5 |
| Pregabalin | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | SensTHAL | 19.4 percent signal change | Standard Error 12.1 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | SensTHAL | 0.8 percent signal change | Standard Error 12.1 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | ACC | 92.5 percent signal change | Standard Error 25.8 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | AIC_L | 103.4 percent signal change | Standard Error 21.8 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | AIC_R | 104.6 percent signal change | Standard Error 20.6 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MIC_L | 105.2 percent signal change | Standard Error 19.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MIC_R | 71.1 percent signal change | Standard Error 17.3 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PIC_L | 44.6 percent signal change | Standard Error 15.9 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PIC_R | 95.5 percent signal change | Standard Error 20 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | Amyg_L | 24.9 percent signal change | Standard Error 16.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | Amyg_R | 57.2 percent signal change | Standard Error 22.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | S1 | 37.7 percent signal change | Standard Error 30.1 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | S2 | 94.6 percent signal change | Standard Error 21.2 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MRF | 25.5 percent signal change | Standard Error 14.6 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | NucCun | 27.7 percent signal change | Standard Error 11.5 |
| Tramadol | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PAG | 53.6 percent signal change | Standard Error 15.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PIC_L | 34.2 percent signal change | Standard Error 15.9 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | NucCun | 40.5 percent signal change | Standard Error 11.5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | S2 | 74.5 percent signal change | Standard Error 21.2 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MIC_R | 92.0 percent signal change | Standard Error 17.3 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MIC_L | 100.4 percent signal change | Standard Error 19.5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | SensTHAL | 10.4 percent signal change | Standard Error 12.1 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | AIC_R | 104.0 percent signal change | Standard Error 20.6 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | ACC | 83.3 percent signal change | Standard Error 25.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | MRF | 37.7 percent signal change | Standard Error 14.6 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | Amyg_L | 36.4 percent signal change | Standard Error 16.5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | AIC_L | 118.7 percent signal change | Standard Error 21.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | Amyg_R | 67.0 percent signal change | Standard Error 22.5 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PIC_R | 91.8 percent signal change | Standard Error 20 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | PAG | 44.6 percent signal change | Standard Error 15.8 |
| Placebo | Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Thermal Stimulation (TH) | S1 | 27.7 percent signal change | Standard Error 30.1 |
Primary
Voxel-wise Blood Oxygen Level Dependent (BOLD) Using fMRI of Brain Activation Signals in Defined Brain Regions in Response to Visual Stimulation (VIS)
BOLD brain activation signals in pre-defined ROI in response to checkerboard visual stimuli (flashing at 2 Hz). ROI were ACC; AIC\_L; AIC\_R; MIC\_L; MIC\_R; PIC\_L; PIC\_R; Amyg\_L; Amyg\_R; S1; S2; SensTHAL; MRF; NucCun; PAG. Prior to ROI analysis, a prelimanary anlysis was performed, wherein it was concluded that ROI analysis was to be carried out for DMAa, DMAc amd TH only.
Time frame: Day 8, 22, 36
Population: For VIS, based on preliminary analysis results, it was not considered significant to collect data according to Investigator's opinion.
Primary
Voxel-wise Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals Across the Whole Brain
BOLD brain activation signals in whole brain was assessed using Contrast Parameter Estimates (COPE) images in response to dynamic mechanical allodynia of the affected side (DMAa), dynamic mechanical allodynia of the control side (DMAc), thermal pain (TH) and checkerboard visual stimuli (VIS).
Time frame: Day 8, 22, 36
Population: Data not available to report, as BOLD brain activation signals in whole brain were obtained as specific Contrast Parameter Estimates (COPE) images only, as per planned analysis.
Secondary
36-Item Short-Form Health Survey (SF-36)
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time frame: Day 8, 22, 36
Population: Data for this outcome measure was plotted against treatment for each participant as per planned analysis but not statistically summarized for analysis.
Secondary
Beck Depression Inventory (BDI)
BDI is a 21 item participant rated inventory evaluating depression symptoms, cognition, and physical symptoms of fatigue, weight loss, lack of interest in sex. Individual items are scored on a 4 point scale (0 to 3), with 0=none/absent and 3=most severe. Total score: 0 to 63; higher score indicate more depression.
Time frame: Day 8, 22, 36
Population: Data for this outcome measure was plotted against treatment for each participant as per planned analysis but not statistically summarized for analysis.
Secondary
Daily Pain Score
Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning using 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). The daily pain scores for an average of the last 7 days and an average of last 3 days were calculated.
Time frame: Day -35 through Day 36
Population: FAS included all the participants who were enrolled in the study. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Daily Pain Score | Last 7 days | 5.57 units on a scale | Standard Error 0.371 |
| Pregabalin | Daily Pain Score | Last 3 days | 5.46 units on a scale | Standard Error 0.466 |
| Tramadol | Daily Pain Score | Last 7 days | 5.28 units on a scale | Standard Error 0.37 |
| Tramadol | Daily Pain Score | Last 3 days | 5.10 units on a scale | Standard Error 0.454 |
| Placebo | Daily Pain Score | Last 7 days | 6.40 units on a scale | Standard Error 0.37 |
| Placebo | Daily Pain Score | Last 3 days | 6.33 units on a scale | Standard Error 0.454 |
Secondary
Doleur Neuropathic 4 (DN4) Score
DN4 questionnaire provides a simple diagnosis of Neuropathic pain (NeP) by asking for yes/no answers to 4 questions (10 sub questions in total). Each question was scored on a scale of 0 (No) and 1 (Yes). Total score was calculated as sum of the 10 individual questions. Total score range 0-10, higher score indicated more neuropathic pain.
Time frame: Day -35
Population: Data for this outcome measure was plotted against treatment for each participant as per planned analysis but not statistically summarized for analysis.
Secondary
Neuropathic Pain Symptom Inventory (NPSI)
NPSI: participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicate a greater intensity of pain.
Time frame: Baseline (Day -7), Day 8, 22, 36
Population: Data for this outcome measure was plotted against treatment for each participant as per planned analysis but not statistically summarized for analysis.
Secondary
Pain Catastrophising Scale (PCS)
The PCS is a self-administered questionnaire with 13 items, each scored from 0 (not at all) to 4 (all the time) for extent to which participant catastrophizes postoperative pain. Total score is sum of scores for all questions (range: 0 to 52); Subscale scores: Rumination (sum of scores for 4 items; range: 0 to 16); Magnification (sum of scores for 3 items; range: 0 to 12); and Helplessness (sum of scores for 6 items; range: 0 to 24); higher scores indicate greater extent of pain catastrophizing.
Time frame: Day 8, 22, 36
Population: Data for this outcome measure was plotted against treatment for each participant as per planned analysis but not statistically summarized for analysis.
Secondary
Present Pain Intensity Score (PPIS)
Participants answered: Please rate your pain from 0-10 that best describes the intensity of pain right now. PPIS assessed on 0-10 numeric rating scale (NRS), 0 (no pain) to 10 (worst possible pain).
Time frame: Day 8, 22, 36
Population: FAS included all the participants who were enrolled in the study. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Present Pain Intensity Score (PPIS) | 5.54 units on a scale | Standard Error 0.552 |
| Tramadol | Present Pain Intensity Score (PPIS) | 4.13 units on a scale | Standard Error 0.551 |
| Placebo | Present Pain Intensity Score (PPIS) | 5.83 units on a scale | Standard Error 0.551 |
Secondary
State and Trait Anxiety Questionnaire
Self-report scale completed by the participant. Separate scales measure state (20 items) and trait (20 items) anxiety. The participant report how they feel right now at this moment for state anxiety and how they generally feel for trait anxiety. The state items are scored as: 1 (not at all), 2 (somewhat true), 3 (moderately true), 4 (very much so). The trait items are scored as: 1 (almost never), 2 (sometimes), 3 (often), 4 (almost always). Scores range from 20-80 for each scale. Higher scores indicate more impaired participants.
Time frame: Day 8, 22, 36
Population: Data for this outcome measure was plotted against treatment for each participant as per planned analysis but not statistically summarized for analysis.