Evaluation of Measuring Instruments for Central Sensitization

This report provides an overview of various measuring instruments used to assess central sensitization, a condition often associated with chronic pain. The report discusses the role of cytokines (IL-1beta, IL-6, IL-8, IL-10, TNF-a) and nerve growth factors (NGF, BDNF, GDNF) in the persistence of pain, detailing how their levels are measured through blood and CSF analysis. It also explores the use of MRI and fMRI in evaluating structural and functional changes related to central sensitization, particularly in conditions like osteoarthritis. The report highlights the instruments and expertise required for each test, including the involvement of physicians, lab experts, physiotherapists, and MRI specialists. It references several studies, including those by Bjurstrom et al. (2016), Lundborg et al. (2010), Deitos et al. (2015), Coppieters et al. (2017), and Sofat et al. (2013), to illustrate the application of these instruments in clinical settings. The report emphasizes the cost and complexity associated with each method, as well as the professionals needed to conduct and interpret the tests.

Running head: MEASURING INSTRUMENTS FOR CENTRAL SENSITIZATION
MEASURING INSTRUMENTS FOR CENTRAL SENSITIZATION
Name of the Student
Name of the University
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Measuring instrument for interleukins: IL-1beta, IL-6, IL-8, IL-10
Chronic pain is one of the major factor that affects the patients of cancer and there are
more than 64 percent of patients affected with such pain. On the other hand, chronic postsurgical
pain or CPSP is another phenomenon that increases the pain related mortality. It has been seen
that cytokines are related to the maintenance and prevalence of chronic pain state, apart from
playing vital role in the peripheral neuroimmune interactions. Researcher Bjurstrom, Girron &
Griffis (2016) researched about the topic and for that, the team conducted a literature review of
previous researches to understand the ole of cytokines and interleukins in the persistence of pain.
Researchers tried to figure out the neurological changes in a rodent with peripheral nerve injury
and noticed that the level of tumor necrosis factor alpha and cytokine becomes upregulated.
Further the experiment was carried out 46 patients within which, 19 were suffering from LR, 21
were suffering from cervical myelopathy and 6 were designated as control. The patients were
provided with pain sensations using pressure from algometer and they were advised to stop the
process whenever they feel extreme pain. Finally it was found that, cytokines, such as IL-1b, IL-
5, IL-6, IL-8, IL-10, and TNF-a were secreting highly during that peripheral nerve damage
sensation (Bjurstrom, Girron & Griffis, 2016). The instruments required for such test needs
expert observation and experience. Therefore, a physician, lab expert or assistant to obtain
accurate result will conduct the test.
Measuring instrument for Nerve Growth Factor
There are different cells in the body, such as skin basal keratinocytes, visceral epithelial
cells in which the nerve growth factors however; there are several factors such as inflammation;
expression of mast cells and macrophages increases the level of NGF in the body. Further,

mutation in NGF and in the receptor for NGF, tyrosine kinase-A leads to partial or complete
insensitivity to pain. According to the Meta analysis study of Bjurstrom, Girron & Griffis (2016),
Lundborg et al. (2010) conducted examined 25 patients with chronic pain to understand the level
of NGF in their body. The Cerebral spinal fluid (CSF) was collected from their lumbar puncture
and all the growth factors were measured in their blood. The researchers found excessive levels
of NGF factor in the CSF and blood of the patients suffering from chronic pain. This is because
after injury in the neurons, the nerve failed to transect the complete nerve fascicule and therefore
sensation of pain was felt to the patients (Bjurstrom, Girron & Griffis, 2016). This test can be
conducted by general physicians who are able to collect CSF and blood samples and conduct
analysis according to that with the help of lab assistant. The cost of the tests are less, as blood
sample analysis and CSF analysis are less expensive. Physiotherapist will also be needed as to
understand the level of pain they will be using their sensory technologies.
Measuring instrument for Brain derived neurotropic factor (BDNF)
There are several aspects of central sensitization and in several disorders such as
fibromyalgia, chronic fatigue syndrome and myofacial pain syndrome, the evidence of structural
pathology is observed. Emergence of pain is also said to be related to expressions of cytokines,
tumor necrosis factors, brain-derived neurotropic factor (BDNF) and interleukins. According to
Deitos et al. (2015), the researchers conducted a cross sectional study, in which they
retrospectively pooled baseline data from five other clinical trials including patients with chronic
pain however, they did not collected the pathological study. They assessed the functional
disability of the patients using a questionnaire. Finally, they selected 81 patients for the final
assessment. A serum test was conducted which was further helped to analyze the neuroplasticity
mediators concentration. A kit for BDNF detection was used and according to the statistical

analysis using Anova test it was found that BDNF is not related to the expression of pain in
patients, however TNF and Interleukins are deeply correlated with the expression of chronic pain
in patients with central sensitization. The instruments required for this test are very costly and
can only be present in laboratories and hospitals and therefore experienced lab workers and
physicians can perform the test with the help of lab assistants.
Measuring instrument for Glia derived neurotrophic factor (GDNF)
Nerves in the peripheral nervous system and central nervous system produce GDNF or
Gilal cell line derived neurotrophic factor and it helps to support the survival of several sub
population of nerves. It further protects and helps to regenerate the nerves and due to its
specificity for the dopaminergic neurons, it is studied in the patients with Parkinson’s disease.
During pain sensations in the peripheral tissues and joints, the chondrocytes produces the GDNF,
as it is generally known as pain attenuator. In the literature review conducted by Bjurstrom,
Girron & Griffis (2016), the researcher mentioned about a research in which Lundborg et al.,
(2010) examined patients with osteoarthritis and were to undergo arthoplastic surgery. The
researchers conducted serum test for all the 25 patients and 6 control subjects and then
statistically analyzed the concentration of GDNF in their serum sample collected from lumbar
puncture. They compared the data with that of the control subjects and they found that the level
of GDNF was higher in serum, where as it was lower in blood sample. Furthermore, they did not
found any correlation between duration of pain and level of GDNF (Deitos et al., 2015). To
conduct the test, instruments such as serum and blood sample collector kit, centrifuge and kit to
detect GDNF are necessary and these instruments are costly. Therefore, microbiologists, lab
technologists, lab pathologists and experienced physicians are able to conduct the test with the
help of registered nurses and lab assistants.

Measuring instrument for MRI
Osteoarthritis (OA) is one of the major reasons for chronic musculoskeletal pain in
patients affected with OA. Loss of grey matter is generally interrelated with the symptoms of
pain vulnerability and reduction of grey matter is also said to be related with the progression of
pain. However, it is not clear that what changes in the skeletal changes lead to pain progression.
Coppieters et al. (2017) conducted a research to find out the relation of surface based
measurements of brain with that of the OA associated chronic pain. They selected 40 patients
with OA and 30 controls and used questionnaires to assess the pain characteristics. Further, they
conducted pain pressure threshold using digital algometer and repetitions were carried out in
index finger, sternum, medial and lateral joints and medial tibia. Further cognitive ability was
carried out using Montreal cognitive assessment test. The magnetic resonance testing of every
patient was done using 32-channel head coil. The results were collected after cortical thickness
and statistical analysis and it was found that thickness of anterior cingulate cortex is not related
to the central sensitization (Coppieters et al., 2017). The test requires an experiences analyst and
very costly instruments. Therefore, general physicians, MRI specialists, physiotherapists and lab
assistants can perform the test using this measuring instrument with the help of each other.
Measuring instrument for fMRI
Hand osteoarthritis is associated with reduced functionality and elevated pain. Following
tissue damage, the inflammation can lead to neurons become more hypersensitive and this
incidence increases in case of central sensitization. To understand the connection between central
sensitization related pain and the hypersensitivity elevated due to osteoarthritis Sofat et al. (2013)
conducted an experiment in patients with hand osteoarthritis (HOA) and non OA controls. Those
patients were with proximal and distal interphalangeal joint (PIP/DIP) to detect the clinical pain,

visual analogue scale (VAS) was used and the assessment was done after the subjects performed
a difficult and task. Further, the central pain processing was assessed using functional MRI and
finger flexion extension was performed for more than 3 minutes. The data was analyzed using
FMRIB software and the results indicated that the thalamus level, cingulate level and
somatosensory cortex was elevated in the patients with HOA, and the regions were present in
higher pain processes in brain. To conduct the study, the instruments with central sensitization
was used and the test can only be conducted by experienced lab professional, who can handle
MRI machinery and physiotherapists to conduct sensory testing and lab assistant.

References
Alshuft, H. M., Condon, L. A., Dineen, R. A., & Auer, D. P. (2016). Cerebral cortical thickness
in chronic pain due to knee osteoarthritis: The effect of pain duration and pain
sensitization. PloS one, 11(9), e0161687.
Bjurstrom, M. F., Giron, S. E., & Griffis, C. A. (2016). Cerebrospinal fluid cytokines and
neurotrophic factors in human chronic pain populations: a comprehensive review. Pain
Practice, 16(2), 183-203.
Coppieters, I., De Pauw, R., Caeyenberghs, K., Danneels, L., Kregel, J., Pattyn, A., ... & Cagnie,
B. (2017). Decreased regional grey matter volume in women with chronic whiplash-
associated disorders: Relationships with cognitive deficits and disturbed pain
processing. Pain physician, 20(7), E1025-E1051.
Deitos, A., Dussán-Sarria, J. A., de Souza, A., Medeiros, L., da Graça Tarragô, M., Sehn, F., ...
& Torres, I. L. (2015). Clinical value of serum neuroplasticity mediators in identifying
the central sensitivity syndrome in patients with chronic pain with and without structural
pathology. The Clinical journal of pain, 31(11), 959-967.
Lundborg, C., Hahn-Zoric, M., Biber, B., & Hansson, E. (2010). Glial cell line-derived
neurotrophic factor is increased in cerebrospinal fluid but decreased in blood during long-
term pain. Journal of neuroimmunology, 220(1), 108-113.

Sofat, N., Smee, C., Hermansson, M., Howard, M., Baker, E. H., Howe, F. A., & Barrick, T. R.
(2013). Functional MRI demonstrates pain perception in hand osteoarthritis has features
of central pain processing. Journal of biomedical graphics and computing, 3(4).