Pain, Inflammation and Fever

1. PAIN, INFLAMMATION AND
FEVER
FARAZA JAVED
PH.D PHARMACOLOGY

2. PAIN
Pain is a distressing feeling often caused by intense or
damaging stimuli. In medical diagnosis, pain is regarded as
a symptom of an underlying condition.

3. The International Association for the Study of Pain widely
used definition defines pain as:
“an unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or
described in terms of such damage”

4. CLASSIFICATION OF PAIN

5. BASED ON DURATION
1. Acute Pain
2. Chronic Pain
a) Chronic Non Cancer Pain
b) Chronic Cancer Pain
c) Chronic Episodic Pain

6. BASED ON LOCATION
1. Headache
2. Back Pain
3. Joint Pain
4. Stomach Pain
5. Cardiac Pain

7. BASED ON INTENSITY
1. Mild Pain (1 to 3)
2. Moderate Pain (4 to 6)
3. Severe Pain (7 to 10)

8. PAIN SCALE

9. BASED ON ETIOLOY
1. Nociceptive Pain
a) Somatic
b) Visceral
2. Neuropathic Pain
a) Peripheral Neuropathic Pain
b) Central Neuropathic Pain

10. Pain is usually transitory, lasting only until the noxious
stimulus is removed or the underlying damage or pathology
has healed, but some painful conditions, such
as rheumatoid arthritis, peripheral
neuropathy, cancer and idiopathic pain, may persist for
years. Pain that lasts a long time is called chronic or
persistent, and pain that resolves quickly is called acute.

11. Traditionally, the distinction
between acute and chronic pain has relied upon an arbitrary
interval of time between onset and resolution; the two most
commonly used markers being 3 months and 6 months
since the onset of pain, though some theorists and
researchers have placed the transition from acute to chronic
pain at 12 months. A popular alternative definition
of chronic pain, involving no arbitrarily fixed durations, is
"pain that extends beyond the expected period of healing".

12. PSYCHOGENIC PAIN
Psychogenic pain is physical pain that is caused, increased,
or prolonged by mental, emotional, or behavioral factors.
Researchers refer psychogenic pain or psychalgia as a form
of chronic pain. Causes may be linked
to stress, unexpressed emotional conflicts, psychosocial
problems, or various mental disorders. Some specialists
believe that psychogenic chronic pain exists as a protective
distraction to keep dangerous repressed emotions such as
anger or rage unconscious.

13. Headache, back pain, or stomach pain are some of the most
common types of psychogenic pain. It may occur in persons
with a mental disorder, but more commonly it accompanies
or is induced by social rejection or other such emotional
events.
It remains controversial that chronic pain might arise from
emotional causes. Treatment may
include psychotherapy, antidepressants, analgesics, and
other remedies that are used for chronic pain in general.

14. MANAGEMENT OF PAIN
Pain van be managed through:
1. Pharmacological Intervention
2. Non Pharmacological Intervention

15. PHARMACOLOGICAL INTERVENTION
Pharmacological therapy is given by analgesics.
1. Analgesics may be Opioids or Non Opioids (NSAID) or
Adjuvants.
2. Adjuvants are drugs originally developed to treat
conditions other than pain but also have analgesic
properties.

16. Adjuvants:
Used for analgesic reasons and for sedation and reducing
anxiety.
1. Tricyclic Antidepressants
2. Antiepileptics
3. Corticosteriods
4. Local Anesthetics

17. WHO Pain Management Ladder

18. WHO Pain Management Ladder
Pain Scale Reading WHO Steps
1-3 Step 1
4-6 Step 2
7-10 Step 3

19. NON PHARMACOLOGICAL THERAPIES
1. Heat and Cold Application
2. Meditation
3. Distraction
4. Imagery
5. TENS Application

20. 6. Music Therapy
7. Massage
8. Yoga
9. Acupuncture
10.Herbal Therapy e.g. Ginseng

21. INFLAMMATION

22. INFLAMMATION
Inflammation is part of the complex biological response of
body tissues to harmful stimuli, such as pathogens,
damaged cells, or irritants, and is a protective response
involving immune cells, blood vessels, and molecular
mediators.

23. The function of inflammation is to eliminate the initial cause
of cell injury, clear out necrotic cells and tissues damaged
from the original insult and the inflammatory process, and
initiate tissue repair.

24. SIGNS OF INFLAMMATION
Cardinal signs are:
Heat (Calor)
Redness (Rubor)
Swelling (Tumor)
Pain (Dolor)
Loss of Function (Functio Laesa)

25. TYPES OF INFLAMMATION
1.Acute
2.Chronic

26. ACUTE INFLAMMATION
Acute inflammation is a short-term process occurring in
response to tissue injury, usually appearing within minutes
or hours.

27. Acute inflammation has two major components:
1. Vascular Changes
2. Cellular Events

28. VASCULAR CHANGES
The process of acute inflammation is initiated by resident
immune cells already present in the involved tissue,
mainly macrophages, histocytes and mast cells. These cells
possess surface receptors known as pattern recognition
receptors (PRRs), which recognize (i.e., bind) two subclasses of
molecules: pathogen-associated molecular patterns (PAMPs)
and damage-associated molecular patterns (DAMPs).
PAMPs are compounds that are associated with
various pathogens, but which are distinguishable from host
molecules. DAMPs are compounds that are associated with host-
related injury and cell damage.

29. At the onset of an infection, burn, or other injuries, these cells
undergo activation (one of the PRRs recognize a PAMP or DAMP)
and release inflammatory mediators responsible for the clinical
signs of inflammation.
Vasodilation and its resulting increased blood flow causes the
redness (rubor) and increased heat (calor).
Increased permeability of the blood vessels results in an
exudation (leakage) of plasma proteins and fluid into the tissue
(edema), which manifests itself as swelling (tumor).
Some of the released mediators such as bradykinin increase
the sensitivity to pain (dolor).

30. CELLULAR EVENTS
The cellular component involves leukocytes, which normally
reside in blood and must move into the inflamed tissue
via extravasation to aid in inflammation. Some act as phagocytes,
ingesting bacteria, viruses, and cellular debris. Others release
enzymatic granules that damage pathogenic invaders.
Leukocytes also release inflammatory mediators that develop and
maintain the inflammatory response.

31. Acute inflammation may be regarded as the first line of
defense against injury. Acute inflammatory response
requires constant stimulation to be sustained. Inflammatory
mediators are short-lived and are quickly degraded in the
tissue. Hence, acute inflammation begins to cease once the
stimulus has been removed.

32. INFLAMMATORY MEDIATORS
Histamine is the main mediator of inflammation. Released from
mast cells and basophils and is the primary cause of increased
vascular permeability.
Prostaglandins are derived by arachidonic acid which can cause
vasodilation, fever, and pain.
Leukotriene is able to mediate leukocyte adhesion and
activation,
allowing them to bind to the endothelium and migrate across it
and is able to induce the formation of reactive oxygen species
and the release of lysosome enzymes by the cells.

33. Cytokines are polypeptide products of activated lymphocytes
and monocytes. The main cytokines participating in acute
inflammation are interleukin-1 (IL-1), interleukin-8 (IL-8), and
tumor necrosis factor alpha (TNFα).
The clotting pathway is responsible for coagulation of blood by
formation of
fibrin from fibrinogen.

34. CHRONIC INFLAMMATION
Chronic inflammation is also referred to as slow, long-term
inflammation lasting for prolonged periods of several
months to years. Generally, the extent and effects of
chronic inflammation vary with the cause of the injury and
the ability of the body to repair and overcome the damage.

35. Chronic inflammation is characterized by less swelling but
presence of more lymphocytes and fibroblasts, which
macrophage have been unable to clear the area of foreign
substances.

36. Chronic inflammation can result from the following:
Failure of eliminating the agent causing an acute inflammation
such as infectious organisms including Mycobacterium
tuberculosis that can resist host defenses and remain in the
tissue for an extended period.
An autoimmune disorder in which the immune system is
sensitized to the normal component of the body and attacks
healthy tissue giving rise to diseases such as rheumatoid
arthritis.

37. Recurrent episodes of acute inflammation. However, in some
cases, chronic inflammation is an independent response and
not a sequel to acute inflammation for example diseases such
as tuberculosis and rheumatoid arthritis.
Exposure to a low level of a particular irritant or foreign
materials that cannot be eliminated by enzymatic breakdown or
phagocytosis in the body including substances or industrial
chemical that can be inhaled over a long period, for example,
silica dust.

40. MANAGEMENT OF INFLAMMATION
1. Nonsteroidal anti-inflammatory drugs (NSAIDs)
2. Steroids
3. Antihistamines

41. FEVER/ PYREXIA

42. PYREXIA
Pyrexia or fever is a physiologic response triggered by
aseptic stimuli or infections which result in elevation of
body temperature due to increased concentration of PGE2
within certain areas of the brain.

43. A fever can be caused by many medical conditions ranging
from non-serious to life-threatening. This
includes viral, bacterial and parasitic infections such as the
common cold, urinary tract
infections, meningitis, malaria and appendicitis among others.
Non-infectious causes include vasculitis, deep vein
thrombosis, side effects of medication, and cancer among
others.

44. Temperature is ultimately regulated in the hypothalamus. A
trigger of the fever, called a pyrogen, causes release
of prostaglandin E2 (PGE2). PGE2 in turn acts on the
hypothalamus, which creates a systemic response in the body,
causing heat-generating effects to match a new higher
temperature set point.
Hypothalamus works like a thermostat. When the set point is
raised, the body increases its temperature through both active
generation of heat and retention of heat.

45. Peripheral vasoconstriction both reduces heat loss through the
skin and causes the person to feel
cold. Norepinephrine increases thermogenesis in brown
adipose tissue, and muscle contraction through shivering raises
the metabolic rate. If these measures are insufficient to make
the blood temperature in the brain match the new set point in
the hypothalamus, then shivering begins in order to use muscle
movements to produce more heat.
When the hypothalamic set point moves back to baseline either
spontaneously or with medication, the reverse of these
processes (vasodilation) and sweating are used to cool the body
to the new, lower setting.

46. MANAGEMENT OF PYREXIA
1. Conservative Measures
(Sponging, Cooling and Proper Hydration)
2. Medication
NSAIDs (PCM, Ibuprofen, Aspirin)

47. THANKYOU