This proposed study suggests that peripheral tissue acidosis sensed by the somatosensory system (sngceptin) would evoke the sng perception in the brain. This hypothesis is based on investigators preliminary data that the peripheral muscle acidosis will evoked the central sng perception. This proposed study also identify the detection of brain activation areas related to the peripheral muscle acidosis. Investigators will know specific brain areas related to sng perception evoked by the peripheral muscle acidosis and, accordingly, a novel mechanism and potential treatment for sng would be developed in this proposed study.
Sng is a prominent complaint in Taiwanese people with low back pain. "Sng" is created to represent this Taiwanese word. Based on investigators preliminary data, sng was one of the most common complaints in patients with chronic low back pain (CLBP) and also one of the most common indication for lumbar spine operations. Back sng is not adequately relieved by pain-killers or even by the lumbar spine operations. By using functional magnetic resonance imaging and questionnaires, the investigators preliminary study demonstrated that sng is different from pain in the level of brain perception and the level of subjective concept. It is very likely that sng has its own unique nerve pathway other than pain. The subjective feeling of sng is very similar to sour in taste, so it is likely that acidosis may be involved in the process of sng sensation, especially in the muscle. Delayed onset muscle soreness is a well-known example, and the soreness is dependent on the proton-sensing neurons. Indeed, substantial evidences showed that up to 80% muscle afferents are acid-sensitive but not nociceptors. Therefore, the investigators propose that sng is the perception in the brain when the tissue acidosis is sensed by the somatosensory system, and "sng-ception" is created to indicate the sensation of tissue acidosis. However, the causal connection between the peripheral sngception and the central brain perception of sng is not established. The objective of this proposal is to establish the causal connection between peripheral muscle acidosis and the central brain sng perception. The investigators central hypothesis is that acidosis-evoked sensation in the muscles will cause a central sng perception in the brain. This hypothesis is based on investigators previous studies that showed sng is different from pain in terms of subjective responses, brain activation areas and clinical impacts. To achieve this goal, two specific aims will be pursued 1. to determine if an acid solution will evokes sng response, and, 2. to detect the brain activation area of sng evoked by an acid solution in functional magnetic resonance imaging. Successful establishment of the casual connection between the peripheral muscle acidosis and the central brain sng perception will lead to a more comprehensive understanding of sng mechanism and the potential medication development.
Phosphate-buffered saline (abbreviated PBS) is a buffer solution commonly used in biological research. It is a water-based salt solution containing disodium hydrogen phosphate, sodium dihydrogen phosphate. The buffer helps to maintain a constant pH. The osmolarity and ion concentrations of the solutions match those of the human body (isotonic).
Taipei Medical University Hospital
Taipei, No.252, Wusing St., Sinyi Dist., Taiwan
RECRUITINGBrain functional magnetic resonance imaging
All images will be acquired on a 3 Tesla MRI system (MAGNETOM Prisma, Siemens, Erlangen, Germany) with a 20-channel head coil. To obtain an anatomical reference, high-resolution T1-weighted imaging was performed using a 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence: repetition time (TR)/echo time (TE) = 2000 ms/3 ms, flip angle = 9°, field of view (FOV) = 256 × 192 × 208 mm3, acquisition matrix = 256 × 192 × 208, resulting in isotropic spatial resolution of 1 mm3. The task fMRI will be performed using an echo planar imaging (EPI) sequence with a twice-refocused balanced echo. The imaging parameters are: TR/TE = 2000/20 ms, slice thickness = 3.5 mm, 80 × 80 acquisition matrix, FOV = 200 × 200 mm, and in-plane spatial resolution = 3.0 mm x 3.0 mm.
Time frame: The whole procedures will be done within 50 minutes. Before the injection, the subject will receive anatomical MRI scan (10 minutes) and baseline fMRI scan (10 minutes) After that, the acid or pH 7.4 PBS will be given into the midpoint of the left tibial
The visual analog scale (VAS) of "sng" in the legs
The subject will be asked for sng VAS before infusion and immediately after infusion. Scale range 0 to 10 (1)0: No Sng (2)1-3: Mild Sng (3)4-6: Moderate Sng (4)7-9: Severe Sng (5)10: Worst Sng imaginable
Time frame: Through fMRI completion an average of 6 months
Muscle pressure pain threshold
Muscle pressure pain threshold on bilateral tibialis anterior muscles will be measured by algometer.
Time frame: Through fMRI completion an average of 1 week
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
52