Systematic Review of Cytokines' Effects on Pain Response

This report presents a systematic review and meta-analysis investigating the effects of cytokines on pain response. The research explores the role of cytokines, including leptin, in modulating pain sensitivity and inflammation. The study examines various research methodologies, including data sources and retrieval techniques, criteria for study inclusion, and data extraction processes. It aims to provide a comprehensive understanding of the relationship between cytokines and pain, analyzing factors such as leptin serum levels, and identifying the rationale for future research and potential therapeutic applications. The report also highlights the importance of understanding the impact of cytokines on pain for developing effective pain management strategies, with a focus on both primary and secondary data collection methods, including experimental and observational studies. The research incorporates the PRISMA criteria for systematic assessments, and the methods section details the search strategy, inclusion criteria, and data extraction procedures, while the results and discussion sections analyze the findings and implications of the cytokine-pain relationship.

The effects of cytokines on pain
response: a systematic review
with meta-analysis
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Table of Contents
ABSTRACT.....................................................................................................................................4
1. INTRDOCUTION.......................................................................................................................4
Research overview......................................................................................................................4
Research background..................................................................................................................5
Aim of the research.....................................................................................................................6
Objectives of the research...........................................................................................................6
Research questions......................................................................................................................6
Rationale of the research.............................................................................................................6
2. METHODS..................................................................................................................................7
3. RESULTS..................................................................................................................................10
3. RESULTS..................................................................................................................................23
4. DISCUSSION............................................................................................................................33
CONCLUSION..............................................................................................................................38
REFRENCES.................................................................................................................................39
APPENDICES...............................................................................................................................41

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
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information. It includes age, medical conditions, genes, gender, emotions and support systems
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 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 picomolar
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concentrations of cytokines are responsible for mediating the biological effects (Hedderson and
et. al., 2020). In context of this investigation, it is based on the aim of analysing the effects of
cytokines on pain response. This 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.
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2. METHODS
2.1. Sources of data and retrieval techniques for research recognition
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
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
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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
The 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.
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 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
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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
inductive research approach because I is favourable for studying facts related to cytokines to gain
accurate outcomes.
Research philosophy
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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 an 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.
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
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
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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-probabilty 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
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
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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 proinflammatory 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 haematopoietins that
promotes cell proliferation & differentiation whereas transforming growth factor beta family
which is responsible for carrying out regulation of immune cells.
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In addition to this, there are multiple cytokines also exist that can be identified in extracellular
milieu at the time of an immunological response can interact in pleiotropic, redundant,
antagonistic and cascade induction. It includes the fact that these interactions are responsible to
make coordinated recruitment as well as activation of whole network of small cells related to
immune systems possible. It is observed that cytokines get activated in an antigen specific way
and it must regulated for avoiding an inappropriate response in host’s system which can be
considered as detrimental for human health respectively. Moreover, the cytokines has important
role for communication the response provided by immune system from one cell to another cell
respectively.
The role of cytokines in health and disease among people
The cytokines plays an important role in order to treat various kinds of health problems
and disease for making an individual feeling relived. It includes the effect of cytokines having
their expanded domain to atherosclerosis as well as cancer besides of several conditions
including immunity, infections and inflammations. Basically, it contains the significance of
cytokines as they are considered as useful biomarkers in respect health and disease along with
acting like diagnostic, prognostic as well as therapeutic agents. As mentioned by Doyle and
Murphy, (2017), it is observed that cytokines are much effective as well as efficient factors
which are supportive in terms of analysing actual health need of an individual to make accurate
decision making of appropriate treatment. It will provide support to deliver correct and better
quality of medical facilities which facilitates to gain improved patient outcomes. However,
cytokines plays an important role as they are significant proteins to carry out cell to cell
signalling to remain involved in physiological procedures like menstruation, pregnancy and
ovulation. It will facilitate proper conduction of physiological process in respect of maintaining
appropriate health condition. Moreover, it is observed that cytokines has various kinds of role in
terms of managing health and disease for improving quality of life of people in which some of
them are mentioned below.
Regulating immunity: This includes the important role of cytokine in terms of regulating the
immune function of human body which is favourable to manage the health problem easily. As
per views provided by Sun and et. al., (2019), it includes the process of cytokines as it is known
as a large group of proteins, peptides or glycoproteins which are secreted via specific cells of
immune system. However, it has been analysed that cytokines can be considered as a significant
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