Pharmacotherapeutics-3, classification, pain pathways, clinical presentation and clinical management of pain.

1. PAIN
MANAGEMENT
T.SOUJANYA
PHARM.D

2. CONTENTS:
• Definition
• Epidemiology
• Classification of pain
• Pathophysiology/pain pathways
• Clinical presentation of pain
• Pain management
• WHO analgesic ladder
• Reference/bibliography

3. DEFINITION:
The word pain is derived from Latin word “peone” and the Greek
word “poine” meaning “penalty or punishment”.
According to “International Association for the Study of Pain”,
the pain is defined as an unpleasant sensory and emotional experience
associated with actual or potential tissue damage or in terms of such
damage.

4. EPIDEMIOLOGY:
Pain is the most common symptoms that provokes people to seek
medical attention. Despite this, the epidemiology of pain is not as well
documented as it is the incidence of many chronic diseases.
1. 50 million Americans are partially or totally disabled because of
pain. The annual cost of pain to American society can be estimated
to be in the million dollars.
2. In the Michigan pain study, 70% of chronic pain patients claimed to
have pain despite treatment, with 22% believing that treatment
worsened pain.

5. CLASSIFICATION OF PAIN:
Pain
Acute pain Chronic pain
Somatic
pain
Visceral
pain
Nociceptive
pain
Neuropathic
pain

6. 1. ACUTE PAIN:
Acute pain is defined as the pain of a shorter duration that
subsides as the healing process occurs. This pain may range from mild
to severity in intensity. Causes of acute pain include:
Post operative pain
Procedural pain
Traumatic pain

7. CONTD…
a) SOMATIC PAIN:
It result of activation of nociceptors (sensory receptors) sensitive
to noxious stimuli in cutaneous or deep tissues. It is experienced locally
and described as constant, aching and gnawing. It is the most common
type in cancer patients.
b) VISCERAL PAIN:
It is mediated by nociceptors. It is described as deep, aching and
colicky. It is poorly localized and often referred to cutaneous sites,
which may be tender. In cancer patients, results from stretching of
viscera by tumour growth.

8. 2. CHRONIC PAIN:
It usually lasts longer than 3-6 months and ranges in intensity
from mild to severe. Chronic pain associated with malignancy includes:
The pain of cancer
Acquired immuno deficiency syndrome (AIDS)
Multiple sclerosis
Sickle cell anaemia
End stage organ system failure

9. CONTD…
a) NOCICEPTIVE PAIN:
It may be visceral or somatic. It is usually derived from the
stimulation of pain receptors. It may arise from tissue inflammation,
mechanical deformation, ongoing injury or destruction. It responds well
to common analgesic medications and non drug strategies.
b) NEUROPATHIC PAIN:
It involves the central and peripheral nervous system. It does not
respond as predictably as nociceptive pain to conventional analgesics. It
may respond to adjuvant analgesic drugs.

10. PATHOPHYSIOLOGY:
The pathophysiology of pain is mainly classified into two
pathways:
1. Nociceptive pathway
2. Neuropathic pathway

11. 1. NOCICEPTIVE PATHWAY:
Nociceptive pain typically is classified either:
Somatic: arising from skin, bone, joint, muscle or connective tissue
Visceral: arising from internal organs such as large intestine/pancreas
The mechanisms involved in nociceptive pathway are:
a) Stimulation
b) Transmission
c) Perception
d) Modulation

12. CONTD…
a) STIMULATION:
The first step leading to sensation of pain is the stimulation of
free nerve endings known as nociceptors. These receptors are found in
both somatic and visceral structures and are activated & sensitized by
mechanical, thermal & chemical impulses.
Noxious stimulus sensitizes and/or stimulates nociceptors and
causes the release of neurochemicals like bradykinins, K+,
prostaglandins, histamine, leukotrienes, serotonin and substance P that
also sensitize and/or stimulate nociceptors. This activation leads to the
production of action potential (AP).

13. CONTD…
b) TRANSMISSION:
The action potential continues from the site of noxious stimulus
to the dorsal horn of spinal cord and then ascends to higher centres in
the CNS. Transmission takes place in at least 5 pathways:
i. Spinothalamic tract
ii. Spinoreticular tract
iii. Spinomesencephalic tract
iv. Dorsal column post synaptic spinomedullary pathway
v. Propriospinal multisynaptic ascending systems

14. CONTD…
c) PERCEPTION:
Conscious experience of pain
d) MODULATION:
Inhibition of nociceptive impulses. Neurons from the brain stem
descend to the spinal cord and release substances such as endogenous
opioids, serotonin and norepinephrine that inhibit transmission of
nociceptive impulses.

15. Noxious (painful) stimuli
1) stimulation
Activation of peripheral nervous system
Production of action potential (AP)
2) Transmission
AP reaches dorsal horn of spinal cord
Activation of CNS at spinal cord
4) Modulation
Transmission of pain signals to brain
Nociception inhibiting neurons
Brain responds to stimuli
(pain) 3) perception

16. 2. NEUROPATHIC PATHWAY:
Neuropathic pain is distinctly differ from nociceptive pain. It is
the pain sustained by abnormal processing of sensory input by the
central or peripheral nervous system.
e.g. low back pain, diabetic neuropathy, post herpetic neuralgia, cancer
related pain, spinal cord injury, multiple sclerosis etc.
The mechanism responsible may be the nervous system’s
endogenous dynamic nature. Nerve damage or persistent nerve
stimulation may cause pain circuits to rewire themselves both
anatomically and biochemically. This produces:

17. CONTD…
a) Spontaneous nerve stimulation
b) Autonomic neuronal pain stimulation
c) Progressive increase in the discharge of dorsal horn neurons
Clinically, patients present with spontaneous pain transmission,
exaggerated painful response to normally noxious stimuli (hyperalgesia)
or painful response to normally non noxious stimuli (allodynia).

18. Nerve damage/ persistent stimulation
Results in
Rewiring of pain circuits both anatomically and biochemically
causing
finally lead to
Neuropathic pain
Spontaneous nerve
stimulation
Autonomic neuronal
stimulation
Increased discharge of
dorsal horn neurons

19. CLINICAL PRESENTATION OF PAIN:
1. GENERAL:
Patients may be in obvious acute distress (trauma pain) or appear
to have no noticeable suffering (chronic/persistent).
2. SYMPTOMS:
i) Pain can be described as sharp, dull, burning, shock like, tingling,
shooting, radiating, fluctuating in intensity and varying in location.
ii) Overtime, the same pain stimulus may cause symptoms that
completely change (e.g. sharp to dull, obvious to vagus).
iii) Non specific symptoms include anxiety, depression, fatigue,
insomnia, anger and fear.

20. CONTD…
3. SIGNS:
i) Acute pain can cause hypertension, tachycardia, diaphoresis,
mydriasis and pallor, but these signs are not diagnostic.
ii) In some acute cases and in most chronic/persistent pain, there may
be no obvious signs.
4. LABORATORY TESTS:
i) Pain is always subjective
ii) There are no laboratory tests that can diagnose pain
iii) Thus pain is best diagnosed based on patient description and history.

21. PAIN MANAGEMENT:
GOALS OF TREATMENT:
1. To decrease intensity and duration of pain
2. To decrease suffering and disability associated with pain
3. Minimize ADRs or intolerance to pain management therapy
4. Monitor and evaluate for therapeutic and unwanted effects
5. Improve patient’s quality of life

22. NON-PHARMACOLOGICAL
TREATMENT:
1. Radiotherapy: For the management of bone metastasis.
2. Physiotherapy: Spinal manipulation, massage, application of heat or
cold.
3. Stimulation therapy: Transcutaneous electrical nerve stimulation
(TENS).
4. Physiological intervention: Cognitive, behavioural and social
therapy.

23. PHARMACOLOGICAL TREATMENT:
1. NON-OPIOID ANALGESICS:
MOA: These drugs except acetaminophen prevent formation of
prostaglandins, produced in response to noxious stimuli, thereby
decrease the number of pain impulses received by the CNS.
Non-opioid analgesics/NSAIDs
Prevent prostaglandin synthesis
Decrease no. of pain impulses
Relieve pain

24. CONTD…
ADRs: GI effects include nausea, vomiting, diarrhea/constipation,
dyspepsia, epigastric pain, bleeding ulceration, hypersensitivity
reactions.
Dose:
• Aspirin: 150-600mg orally BD
• Acetaminophen: 325-650mg orally
• Meclofenamate: 50-100mg orally
• Mefenamic acid: 250-500mg orally
• Etodolac: 400mg or 200-400mg orally
• Diclofenac: 50-100mg IM or orally

25. CONTD…
2. OPIOID ANALGESICS:
MOA: Opioids produce their actions by interacting with various opioid
receptors (µ,δ,κ) that are located in spinal, supra spinal and peripheral nerves.
Opioid analgesics
binds
Opioids receptors
Activation of opioid receptors
Close voltage sensitive Ca+2 channels & stimulate K+ efflux
Decreases transmission of nociceptive impulses

26. CONTD…
ADRs: Nausea, vomiting, constipation, respiratory depression,
hypotension due to vasodilation, drowsiness, confusion, itching, skin
rashes etc.
Dose:
• Morphine: 10-50mg orally or 10-15mg IM or SC
• Codeine: 30-60mg orally
• Methadone: 2.5-10mg oral/IM
• Tramadol: 50-100mg oral/IM

27. 3. ADJUVANT DRUGS:
a) Tricyclic antidepressants: Amitriptyline
b) Anti convulsants: Carbamazepine, sodium valproate
c) Corticosteroids: Prednisolone, dexamethasone
d) Anxiolytics: Diazepam, lorazepam
e) Muscle relaxants: Baclofen

28. WHO ANALGESIC LADDER:

29. REFERENCE/BIBLIOGRAPHY:
Textbook of Pharmacotherapy:
A Pathophysiologic approach by
Joseph T. Dipiro.