Effects of Cytokines on Pain Response: Systematic Review with Analysis

This report presents a systematic review and meta-analysis of the effects of cytokines on pain response. The research investigates the role of cytokines, including leptin, in modulating pain and inflammation. The study examines various research methods, including data sources, study selection criteria, and data extraction techniques. The objectives include understanding cytokines, their role in health and disease, and their impact on pain sensitivity. The research questions address the effects of cytokines and leptin on pain sensitivity. The report details the methods used, including a meta-analysis of studies from databases like OVID, MEDLINE, EMBASE, and Science. The criteria for study inclusion, data extraction, and assessment of study methodology are described. The findings are presented, followed by a discussion of the implications and a conclusion summarizing the key insights. The research aims to contribute to the understanding of pain mechanisms and potential therapeutic targets.

The effects of cytokines on pain
response: a systematic review
with meta-analysis
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Table of Contents
Table of Contents.............................................................................................................................2
ABSTRACT.....................................................................................................................................3
1. INTRDOCUTION.......................................................................................................................3
Research overview..................................................................................................................3
Research background..............................................................................................................4
Aim of the research................................................................................................................5
Objectives of the research......................................................................................................5
Research questions.................................................................................................................5
Rationale of the research........................................................................................................5
2. METHODS..................................................................................................................................5
3. RESULTS..................................................................................................................................10
3. RESULTS..................................................................................................................................23
4. DISCUSSION............................................................................................................................33
CONCLUSION..............................................................................................................................38
REFRENCES.................................................................................................................................39
APPENDICES...............................................................................................................................42

ABSTRACT
This is a systematic review of cytokines effects on pain response. Cytokines can be
defined as an important group of components including proteins, peptides and glycoprotein
which plays an important role in terms of managing different physiological functions including
modifying pain responses. The role of cytokine modulation of pain and neural dysfunction along
with this provide better rationale for therapeutic which is uses the anti-cytokine agent in human
painful degenerative diseases. In this research proper understanding about the cytokines. The
role of cytokine in the health or disease in individual has been determined. The relationship
between leptin and pain has been successfully analysed in order to gather more relevant and
accurate information. There are various methods has been consider in order to collect and gather
effective information as well as better decision making process.
1. INTRDOCUTION
Research overview
Pain can be defined as a kind of distressing feeling often caused due to an intense or damaging
stimulus. It can be considered as an unpleasant sensory and emotional experience connected with
actual or potential tissue damage or described in terms of such damage. Chronic pain refers to a
condition of pain which remain for at least 12 weeks which includes the feeling or sharp or dull
causing aching or burning sensation in the affected areas of human body. It includes some of
prevalent chronic pain conditions such as headache, postsurgical pain, post trauma pain, lower
back pain, arthritis pain, neurogenic pain caused by nerve damage and psychogenic pain (Kremer
and et. al., 2016). Leptin is consider as the appetite regulatory hormone which is also known as
the act of pro inflammatory adipokine. Leptin mediated inflammation is associated with
increased pain sensitivity. However, the experimental pain can be defined as a condition which
is responsible for causing relatively greater activity of the lateral pain pathway at the time of
induced arthritic pain at the same intensity cause relatively greater activity in the medial pain
pathway. There are number of factors which are responsible for effecting pain experience like
biological factors and psycho-social factors. There are different elements of research
methodology which needs to be analyse and evaluated properly. Primary and secondary method
are significant for collecting most accurate data in order to successfully determine the required
information. It includes age, medical conditions, genes, gender, emotions and support systems
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which affect that pain experienced among people. Pain can also be affected by a group of
compounds referred to as cytokines (include a reference).
Cytokines refers to a large group of proteins, peptides or glycoproteins which are
produced by specified cells of immune system. An example of these substances is Leptin. Leptin
can be described as a kind of protein that is known as cell signalling hormone vital in regulation
of appetite, food intake and body weight. Leptin play significant role in body that includes
regulation of energy homoeostasis, neuroendocrine function and metabolism. It will effect over
regulation of immune function and bone metabolism (Younger and et.al., 2016). Basically, it is
necessary to leptin counteracts the effects of feeding stimulant released in gut which is known as
neuropeptide Y and effects of cannabinoid that is responsible for stimulating the appetite
(Missair and et. al., 2019).
It is required to carry out study on effects of leptin on pain sensitivity and analyse the
relevant facts and findings (Azim and et.al., 2018). It is necessary to understand role of leptin in
terms of pain so that effective pain treatments can be developed. However, it is required to
investigate about leptin-mediated inflammation related to It really is essential to note that a
company's revenue at the end of the learning month did not actually imply that the corporation
seems to have that much money rolling in for the respective year. enhanced pain sensitivity. The
relationship between leptin and inflammation will lead to have particular impact over
concentrated on chronic inflammatory rheumatic diseases. It has been determined that both leptin
and BMI were found to be independently associated with self-reported pain.
Research background
The cytokines can be considered as an effective category of signalling molecules which are
responsible for mediating and regulating immunity, inflammation and haematopoiesis. It is
observed that cytokines are developed from cells of human body of diverse embryological origin.
Basically, it includes the fact that the cytokine is just a general term but their names are specified
on basis of their presumed function, cell of secretion or target of action. It consist the example
that cytokines produced by lymphocytes are known as lyphokines and cytokines secreted by
macrophages or monocytes are called as monokines (Lippi and et.al., 2017). It is observed that
cytokines and their receptors exhibit very high affinity for each other due to which Pico molar
concentrations of cytokines are responsible for mediating the biological effects. In context of this
investigation, it is based on the aim of analysing the effects of cytokines on pain response. This
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study will focus on basic understanding about cytokines and their role in health & disease among
people. It will also include different types of cytokines with their respective functions in human
body. The effective analysis about the effects of leptin serum levels on the pain sensitivity to
understand actual facts about the same is given below.
Aim of the research
“To analyse the effects of leptin on pain response.”
Objectives of the research
 To identify the basic understanding about cytokines.
 To evaluate the role of cytokines in health and disease among people.
 To determine the various types of cytokines with their respective functions.
 To examine the effects of cytokines on pain response.
 To analyse the effects of leptin serum levels on the pain sensitivity.
 To identify the relationship between cytokines and pain.
Research questions
 Does cytokines and leptin serum levels effects the pain sensitivity?
Rationale of the research
In context of this investigation, it has an importance to study about facts and figures related to
impact of cytokines on pain. It is necessary to analyse the actual effects of cytokines on pain
response according to which specific clinical procedures of treatment can be developed. It is
required to evaluate the actual causes and effects related to cytokines on pain response among
human beings so that desired clinical methods as well as techniques can be enhanced for
providing better care facilities to people wellbeing (Smith, Hébert and Veluchamy, 2020).
However, this study has another rationale of evaluating the effects of leptin in respect of
regulating the pain sensitivity among people so that desired hormones can balanced by inducing
specific medication to improve the health condition of an individual. It will provide support to
gain appropriate knowledge about leptin related pain sensitivity in order to manage the relevant
condition of an individual effectively in future.
2. METHODS
2.1. Sources of data and retrieval techniques for research recognition
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Meta-analysis is used in this research which is known as a systematic strategy for combining
quantitative data of several empirical research addressing the influence of an independent
variable (or determinant, or intervention, or therapy) on a specific outcome is known as meta-
analysis (or dependent variable). Meta-analysis is increasingly being utilized in the social
sciences as a method for hypothesis testing. It was first created in medical and psychological
research as a method for synthesizing empirical evidence regarding treatment effects. The
assumptions that underpin meta-analytic hypothesis testing in the social sciences, on the other
hand, are seldom satisfied in real-life situations. This is why meta-analysis is increasingly being
done with a difference.
The Recommended Reporting Elements for Systematic Assessments (PRISMA) criteria were
included in this analysis. Searches for OVID, MEDLINE, EMBASE and Science were identified
by studies conducted between January 1950 and May 2017. The following keywords and MeSH
phrases are directly used: [pain sensitivity OR experimental pain OR calculation of pain OR
quantitative sensory measures OR pressure pain levels OR thresholds of heat pain] AND [obesity
OR overweight OR BMI]. In the reference list of the papers, we have manually scanned for
related studies.
2.2. Criteria for this study for considering studies
There were following methods used in this research -
Post-puberty utilisation of stable human volunteers (i.e.>16 years);
Measured reaction to pain evoked experimentally (e.g. pain threshold, pain resistance, severity or
intensity of pain)
Rating for unpleasantness);
By calculating body mass index (BMI, e.g. weight and height) and/or body mass index (e.g.
weight and height), obese and non-obese participants were compared.
2.3.-2.3. Choice of Research
In order to classify potentially important studies, two reviewers (RA, OAT) screened titles and
abstracts separately. Reviewers were not oblivious to the effects of titles, organisations, papers,
or research. Reports in detail of theoretically important studies was collected and tested for
inclusion by RA and OAT. Disagreements with the entire evaluation committee with MIJ serving
as arbiter have been settled by consensus.
Oh. 2.4. Extracting Info
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Data were derived separately from included RA and OAT trials including number of subjects,
age and sex, metrics to categorise people into categories (e.g. non-obese and obese), laboratory
procedure of pain (e.g. noxious stimuli) and assessments of pain outcome. It tested and reported
the consensus between the two reviewers.
Systematic review
A systematic review can be describe as the process of answering the defined research
questions by collecting as well as summarising all empirical evidence which fits pre specified as
per the eligibility criteria
Meta-analysis
Meta-analysis is refer the use of statistical method in order to summarise the results of the
study. This is significant for correctly analysing and determining the information which is
significant for better decision making.
2.1. Data Sources and Search Methods for Identification of Studies
They are different sources and methods which is significant for better data collection. It is
crucial that researcher is consider different sources in order to successfully gather information as
well as correctly conduct research practices (Hedderson and et. al., 2020).
2.2. Criteria for Considering Studies for this Review
The selection criteria that has been considered for this study is 50 respondents. All of
these respondents are above age 18 and they are participating as per their own will as well as
proper information.
2.3. Study Selection
This refer as the method which is consider for selecting the respondents in order to gather
more accurate information. In this random sample is considered for the study selection.
2.4. Data Extraction
Data extraction refer as the study which includes number of participant along with their
age, gender, measurement to individual. For data extraction questionnaire approach has been
used as this is significant for collecting and extracting data in most effective manner.
2.5. Assessment of Study Methodology, Outcome and Heterogeneity
Types of investigation
The investigation can be divided into two sections such as qualitative and quantitative
method research from which suitable is required to be selected by investigator according their
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respective study. Initially, the qualitative research method can be defined as technique in terms
of gaining an understanding of underlying reasons and motivations (Snipe and et. al., 2018). It
includes the criterion to uncover prevalent trends in thought and opinion in which data collection
was non-statistical. Meanwhile, it consist use of small number of subjects at the time of selecting
sample and use mostly primary data collection methods like interview, focus groups,
questionnaire etc. In contrary to this, the quantitative method of research is quantify the data and
generalised results from a sample to population of interest. It includes to focus on statistical data
for gaining accurate findings by carrying out effective analysis of information. This study will
focus on qualitative research method to gain appropriate information in detail in order to gain
accurate findings.
Research design
The research design refers to a kind of research strategy which is helpful to carrying the
study in effective as well as efficient manner. It can be categorised into several categories such
descriptive, exploratory and experimental research design from which specific one should be
used in research. Meanwhile, the descriptive research design can be described as an effective
method that is favourable to define the features of specific target population or the specific
phenomenon which is required to be studied (Noack and Miossec, 2017). It includes the use of
descriptive research design at wide variety of investigations to investigate one or more variables.
However, the exploratory research design is used for carrying out the study of specific problem
when investigator has lack of past data or only few studies for references. Moreover, the
experimental research design is applicable in order to conduct experiments which is used mostly
in science researches. In context of this investigation, it will focus on descriptive research design
which is suitable to study on effects of cytokines and leptin effects on pain sensitivity.
Research approach
Research approach refers to the appropriate plan and procedure which incudes to conduct
steps of broad assumptions regarding detailed methods of collecting relevant information,
analysis and interpretation. It includes the criterion of following appropriate plan of action in
order to conduct the appropriate investigation for gaining accurate findings (Mangalmurti and
Hunter, 2020). However, the research approach can be categorised into two sections such as
inductive and deductive from which suitable one is required to be selected to use by researcher
according to research problems and nature of the study. In context of this project, it will focus on
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inductive research approach because I is favourable for studying facts related to cytokines to gain
accurate outcomes.
Research philosophy
Research philosophy can be defined as an appropriate belief of the effective way in terms
of specific phenomena to collect, analyse and use the relevant data. It includes the accurate
statement which can be considered as an important element in terms of carrying out investigation
properly. However, it has been analysed that appropriate research philosophy should be selected
by a researcher according to their specific research aim to conduct study effectively (Snipe and
Costa, 2018). In context of this project, it will focus on the research philosophy of interpretivism
to carry out investigation regarding impact of cytokine on pain response in order to gain accurate
findings.
Data analysis
Data analysis can be explained as procedure of cleaning, transforming and modelling of
gathered information related to specific research topic. It includes to carrying out analysis of
collected information and facts about the specific research aim for evaluating the actual facts in
order to achieve accurate findings. However, it has been analysed that data analysis includes
number of methods from which suitable one should be chosen by investigator in order to
interpret the respective findings (Mirzaei and et. al., 2019). It is necessary to thoroughly
investigate the entire collected data and analyse the facts in respect of interpreting accurate
findings. The thematic analysis method will be considered for data interpretation and discussion
based on collect information in this research. It will facilitate to interpret the attained findings in
appropriate manner.
Dealing with missing data
The number of studies included in the analysis and the characteristic of each study
The various source that has been searched for current study are provided as below:
Authors Study design Population Outcome
Ayoub, S., observational 40 Cytokines, Masticatory Muscle
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Berbéri, A. and
Fayyad-Kazan, M.,
2020.
study participants
of HCQ
Inflammation, and Pain: an
Update. Journal of Molecular
Neuroscience,
Burke, N.N., Fan,
C.Y. and Trang,
T., 2016
Experimental 10
participants
Microglia in health and pain: impact of
noxious early life events. Experimental
physiology,
Ebersberger, A.,
2018
Case study Not
applicable
The analgesic potential of cytokine
neutralization with
biologicals. European journal of
pharmacology
Lurie, D.I., 2018 Integrative
approach
Not
applicable
Neuroinflammation in psychiatric
disorders and neuropathic pain. Journal
of Experimental Neuroscienc
Data collection method
The data collection methods are divided into primary and secondary sources from which
desired information can be gathered. It is very important to study the information and gather
relevant data carefully which impact positively to increase the accuracy of research findings. It
will facilitate to make them more reliable to be applied for future perspectives. The primary data
can be considered as first hand data as it was not used previously by other researcher for their
respective investigations. It includes the se of several primary methods such as questionnaire,
survey, focus groups, interview etc. in order to carrying out study with the help of gathering
accurate information (Verrico and et. al., 2020). However, it has been analysed that secondary
data is known to be second hand information because it was used previously by other researchers
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for their investigation. It includes the use of several secondary sources of data collection
including books, journals, articles, websites, magazines, newspapers and so on. This
investigation will focus on use of primary source of questionnaire for data analysis and
secondary sources for carrying out literature review.
Sampling method
Sampling refers to the phenomenon of selected more eligible subjects related to target
population in order to gather appropriate information which impact positively to achieve accurate
findings of the study. It includes the different kinds of sampling methods such as probability and
non-probability sampling methods which have their sub parts from that appropriate method can
be selected for this investigation (Sommer, Leinders and Üçeyler, 2018). However, it includes
the method of probability sampling such as simple random sampling, systematic sampling,
stratified sampling and cluster sampling method. Moreover, the non-probability sampling
method consist the sub parts including quota sampling, convenience sampling, purposive
sampling, self-selection sampling and snowball sampling. The random sampling method will be
used for this investigation by considering the sample size including group of 50 respondents.
Ethical considerations
Ethical consideration includes important ethical factors which plays an important role to
facilitate the entire investigation in correct direction. It includes the criterion of avoiding wrong
inaccurate attempts during the research process which impact positively on respective outcomes.
However, it is necessary for researcher to use all the ethical principles such as informed consent,
beneficence, maleficence, honesty, trustworthiness, justice and confidentiality which is
favourable to gain accurate as well as reliable findings respectively (Suzuki, 2018). Moreover,
the researcher follow all the ethical requirements in this study while conducting the study about
impact of cytokine on pain response in order to attain appropriate research outcomes.
3. RESULTS
The basic understanding about cytokines
According to views given by Lurie, (2018), Cytokines can be considered as small
secreted proteins produced with the help of cells having specific impact on interactions as well as
communications between cells. The word cytokine has been derived from Greek words that is
cyto means cells and kinos meaning movement.it has an important role to communicate about
the immune response form cell to cell along with stimulating the correct movement of cells
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towards specific sites related to infection, trauma and inflammation. The cytokine may exhibit
several actions that are mentioned here. Initially, it consist the autocrine action with the help of
binding to receptor on the membrane of the same cell that developed it. Secondly, it includes the
paracrine action in which it gets bind with the receptors on a target cell in close proximity to the
producer cell. Thirdly, it involves the endocrine activity via travelling through circulation and
acting on target cells in distant parts of the bod. It has been analysed that cytokines are
accountable for carrying out regulation of cellular activity in specific coordinated interactive
pathway because of several attributes. The first attribute is pleiotrophy which states that single
cytokine has many different functions. It includes the redundancy which states that several
various cytokines ate capable to mediate the similar or same functions. However, it consist the
fact that synergism takes place when the combined effect of two cytokines on cellular activity is
greater than additive impacts of individual cytokines. It consist final attribute of antagonism
includes that effects of single cytokine inhibits or offsets the impacts of another cytokine.
On the other hand, it has been evaluated that leptin can be considered as an effective hormone
which has role of regulating appetite that is known as pro inflammatory adipokine. It includes the
fact that this hormone has one more important effect for increasing systematic leptin
concentrations which may be able to have greater sensitivity in terms of pain. As per opinion of
Burke, Fan and Trang, (2016), it is responsible for administrating in human beings in respect of
elevating the number of clinical markers of systematic inflammation that is linked with enhanced
pain sensitivity. It includes the fact that leptin mediated inflammation is connected with the
increased pain sensitivity condition. However, it is observed that cytokines generally exits in the
form of protein, peptide and glycoprotein which is an attached form of protein with sugar. It
includes the involvement with receptor that triggers intracellular signalling cascades leads to
altered gene expression in the target cell, which leads to specific biological effect. It consist the
differentiation, proliferation and activation of target cell are all effects that can be identified dater
cytokine stimulation. Moreover, cytokines includes interferon family that has antiviral proteins,
chemokine family which direct the cell migration adhesion and activation. McSorley, Horgan
and McMillan, (2016) states that it includes the tumour necrosis factor family that regulates
inflammatory & immune responses and interleukin family which has variety of actions
dependent upon interleukin as well as cell type. Furthermore, it consist haematopoiesis that
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