This document provides an overview of pain pathophysiology and management. It begins with objectives and introduces topics like neuroanatomy, pathophysiology, types of pain, assessment, and management. It describes how pain is a subjective experience transmitted by nociceptors and modulated by various factors. The neuroanatomy of pain transmission from the periphery to the CNS is outlined. Different types of pain like nociceptive, neuropathic, referred, acute, and chronic are defined. Common pain syndromes and their characteristics are mentioned. Non-opioid and opioid medications as well as non-pharmacological approaches for pain management are summarized.

1. PATHOPHYSIOLOGY AND
MANAGEMEMENT
OF PAIN
DR. SUBODH KUMAR MAHTO,
DEPT. OF MEDICINE
PGIMER,DR.RML HOSPITAL.
NEW Delhi

2. OBJECTIVES
 INTRODUCTION
 NEUROANATOMY
 PATHOPHYSIOLOGY
 TYPES OF PAIN
 HISTORY
 ASSESSMENT OF PAIN
 MANAGEMENT

3.  Pain is an unpleasant , sensory and emotional experience
usually associated with noxious stimuli
 Pain is
◦ Subjective
◦ Protective
◦ And it is modified by developmental, behavioral
personality and cultural factors

4.  The word “pain” is derived from the Latin word “poena”
meaning fine, penalty, or punishment.
 Pain Threshold – level of noxious stimulus required to alert
an individual of a potential threat to tissue
 Pain Tolerance – amount of pain a person is willing or able to
tolerate

5.  A person experience pain through
◦ Sensory- discriminative system: this processes the
information about the strength, intensity, quality, spatial,
temporal aspects of pain.
◦ Motivational- affective system: It determines the
individuals avoidance- approach behavior.
◦ Cognitive –evaluative system: It overlies the individuals
learned behavior concerning the experience of pain. It
may block, modulate or enhance the perception of pain.

6. Types of nerve fibers

7. Large fibre Small fibre
Unmyelinated Myelinated
Slow conducton Fast conduction
Responds to thermal chemical and
mechanical stimuli
Responds to mechanical and
mechanothermal stimuli
Produces sensation of sharp
pain(epicritic pain)
Produces sensation of dull
pain(protopathic pain)

8. Neuroanatomy of pain
 The areas of nervous system responsible for pain
pathways are:
 Afferent pathways
 CNS
 efferent pathways

9. Pain pathway
 Afferent pathways terminate in the dorsal horn of the spinal
cord(1st order neuron)
 The nerve fibers from the dorsal root ganglia enter the spinal cord
through dorsal root and send branches 1-2 segments up and down
the spinal cord.
 Second order neurons transmit the impulse from the substantia
gelatinosa and lamina through the ventral and lateral horn
crossing the same or adjacent segment to the other side of the
cord.

10. Pain pathway
The impulse is then carried through the spinothalamic tract
to the somatosensensory cortex, frontal cortex and cingulate
gyrus. There are two divisions of spinothalamic tract which
transmit in different areas of brain.
 Neospinothalamic tract
 Paleospinothalamic tract
Neospinothalamic tract projects to VPL nucleus of thalamus.
Paleospinothalamic tract projects to central nuclei of
Thalamus.

12. PHYSIOLOGY OF PAIN

13. Peripheral mechanisms of pain

14. Mediators

15. Neurotransmitters
 Pain Initiators
◦ Glutamate - Central
◦ Substance P - Central
◦ Brandykinin -
Peripheral
◦ Prostaglandins -
Peripheral
 Pain Inhibitors
◦ Serotonin
◦ Endorphins
◦ Enkephalins
◦ Dynorphin

16. Sensitization
 When intense, repeated, or prolonged stimuli are applied to
damaged or inflamed tissues, the threshold for activation is
lowered, and the frequency of firing is intensified.
 mediators - bradykinin, nerve-growth factor, and leukotriene
 Sensitization occurs
◦ At peripheral nerve terminal (peripheral sensitization)
In damaged or inflamed tissues an increase in the production,
transport, and membrane insertion of chemically gated and
voltage-gated ion channels occurs.
◦ At the dorsal horn of the spinal cord (central sensitization).

18. Pain modulation pathway

20. Endogenous Opioid Systems

21. Gate-Control Theory –
Ronald Melzack (1960s)
 Described physiological mechanism by which
psychological factors can affect the experience of pain.
 Neural gate can open and close thereby modulating
pain.
 Gate is located in the spinal cord in SG.
 When the gate is closed signals from small diameter
pain fibres do not excite the dorsal horn transmission
neurons.
 When the gate is open pain signals excite dorsal horn
transmission cells

23. Gate control theory

24. Three Factors Involved in Opening and
Closing the Gate
 The amount of activity in the pain fibers.
 The amount of activity in other peripheral fibers.
 Messages that descend from the brain.

25. Conditions that Open the Gate Conditions That Close the Gate
 Physical conditions
◦ Extent of injury
◦ Inappropriate activity level
 Emotional conditions
◦ Anxiety
◦ Tension
◦ Depression
 Mental Conditions
◦ Focusing on pain
◦ Boredom
 Physical conditions
◦ Medications
◦ Counter stimulation (e.g.,
heat, massage)
 Emotional conditions
◦ Positive emotions
◦ Relaxation, Rest
 Mental conditions
◦ Intense concentration or
distraction
◦ Involvement and interest in
life activities

26. Types
 Pain can be categorized according to inferred pathology:
Nociceptive pain
Somatic - Skin, tendons, ligaments, bone etc..
Visceral – Organs, cavity linings
Neuropathic pain- stimuli abnormally processed by the
nervous system. Ex- diabetic neuropathy, phantom limb
pain.
Referred pain
 By duration:
 Acute
 Chronic

27. Somatic pain
 Source: Skin, muscle, and connective tissue
 Examples: Sprains, headaches, arthritis
 Description: Localized, sharp/dull, worse with
movement or touch
 Pain med: Most pain meds will help, if severe, need a
stronger medication

28. Visceral pain
 Causes
Abnormal distention and contraction of the hollow viscera
muscle walls
Rapid stretching of the capsule
Abrupt anoxemia
Direct action of chemical stimuli (oesophagus)
Traction or compression of ligaments and vessels
Inflammatory processes and Necrosis of some structures
(myocardium)

29. Visceral pain
 Characteristic features of visceral pain
It is dull aching, deep, not well defined, and differently
described by the patients
Difficult to locate
Induces strong autonomic reflex phenomena
Much more pronounced than in pain of somatic origin
(psychic alarm reaction -"angor animi" - in angina pectoris)

30. Referred pain
Figure 10-13b
Skin
(usual stimulus)
Kidney
(uncommon stimulus)
Primary sensory
neurons
Secondary
sensory
neuron
Ascending sensory
path to somatosensory
cortex of brain(b)

31. Acute pain
 It is a protective mechanism that alerts the individual to a
condition that is immediately harmful to the body. Which
leads to the following responses:
◦ Increased HR & RR
◦ Elevated BP
◦ Pallor or flushing, dilated pupils
◦ Psychological and behavioural response to acute pain
 Fear
 General sense of unpleasantness
 Anxiety

32. Chronic pain
 It is persistent or intermittent usually defined as lasting at least 3-
6 months
 The cause is often unknown, often develops insidiously, very often
is associated with Depression.
 Chronic pain produces significant behavioural and psychological
changes:
depression
an attempt to keep pain - related behaviour to a minimum
sleeping disorders
preoccupation with the pain
tendency to deny pain

33. Common pain syndrome
 Neuropathic pain
1. Peripheral nerve
pain
2. Central pain
 CRPS
 Pain in association with
psychiatric disease
 Chronic pain of
indeterminate cause
 Cancer pain
 Post stroke pain
syndrome
 Cervicogenic headache
 Low back pain
 Migraine
 Phantom limb pain.
 Neuralgias

34. Neuropathic pain
 Dysesthesia-Any abnormal sensation described as unpleasant
by the patient
 Hyperalgesia- Exaggerated pain response from a normally
painful stimulus
 Hyperesthesia (hypesthesia) - Exaggerated perception of touch
stimulus
 Allodynia - Abnormal perception of pain from a normally
nonpainful mechanical or thermal stimulus
 Analgesia - Reduced perception of pain stimulus
 Paresthesia - Mainly spontaneous abnormal sensation that is
unpleasant; usually described as "pins and needles"

36. Complex regional pain syndrome
 Old terminology - Casualgia.
 It is a painful condition that includes regional pain, sensory
changes, abnormal sudomotor activity , skin changes, edema
following an inciting event such as trauma.
 Commonly seen in females in 3rd n 4th decade
 Precipitating factors:
-Fracture -Strain/ sprain
-Post surgery -Crush injury

37.  Types
CRPS I- No definable nerve lesion
CRPS II- Involves nerve lession.
 C LINICAL FEATURES:
 Excruciating pain
 Edema of affected limbs.
 Autonomic dysfunction.
 Motor dysfunction.

38. Cancer pain
 Mechanism
Direct tumour invasion of local tissues.
Metastatic bone pain.
Osteoporotic bone and degenerative joint pain in older
people.
Visceral obstruction.
Nerve compression and plexus invasion.
Ischaemia.
Inflammatory pain.
Chemotherapy induced neuropathy, paraneoplastic
neuropathy and arthropathy.
 Post-surgical pain and radionecrosis.

39. Post stroke pain syndrome
 Patients complaints of spontaneous severe paroxysmal and
burning type pain sensation.
 It has been postulated that damaged sensory pathways or
damage to the central inhibitory may be responsible for
pain.
 Following stroke about 40- 60 % patients develop shoulder
pain. It usually improves following physiotherapy.

40. Phantom limb pain
 Phantom = ghost. Phantom limb feels real. Sometimes
amputees try to walk on their phantom limb.
 Several studies have shown that 75% of patients with
PLP develop pain within the first few days after
amputation.
 Usually intermittent; only few patient’s are in constant
pain. Located in distal parts of the missing limb.
 Mechanism- stump neuroma, spinal plasticity , cerebral
reorganization.
 Treatment – multi disciplinary approach. TCAs, TENS,
Mirror box therapy etc..

41. Cerebral reorganization.

42. Mirror box therapy
 Persons with amputated limb use either a mirror or
mirror box to reflect an image of the intact limb. It is
hypothesized that this works by preventing cortical
restructuring

43. History
 Site of pain
Primary location
Radiation
 Circumstances associated with pain onset including details of
trauma or surgical procedures
 Character of pain - Sensory descriptions eg sharp, throbbing,
aching
 Intensity of pain
 At rest
 Movement

44.  Temporal factors
 Duration
 Current pain, during last week
 Aggravating or Relieving factors
 Associated symptoms (eg nausea)
 Effect of pain on activities and sleep
 Treatment history
 Current and previous medications
 Other treatment eg. transcutaneous
electrical nerve stimulation

45. Assesment of pain
 McGill pain questionnaire
◦ Part I - To localize the pain
◦ Part II- Incorporates the visual analogue scale.
◦ Part III- The pain rating index. It includes 20
categories and 76 descriptions.

46. VISUAL ANALOG SCALE

47. Neuropathic pain
questionnaire

48. Treatment

49. Classes of medication
 Non narcotic
analgesics
 Narcotics
analgesics
 Anti depressants
 Anti convulsants
 Anti arrythmics
 Muscle relaxants
 Complementary
and alternate
medicine:
 Hyperbaric
oxygen.
 Acupuncture.
 Electrical
stimulation
devices.
 Trigger point
injections.

50. Pain ladder approach

51. Adjuvant therapy ‐
 Tricyclic anti‐depressants
 Anticonvulsant medications – Gabapentin, Pregabalin, and
Carbamazepine
NSAIDs (non‐steroidal anti‐inflammatories) ‐ can be used
as co‐analgesics and are useful in reducing inflammation

52. NSAIDS
Drugs dosages Adverse effects Uses
Acetylsalicylic
acid
650 mg PO Reye’s syndrome in children
Avoid in women in late
pregnancy, kidney or liver
disease, asthma, high blood
pressure, or bleeding disorders.
Peptic ulcer.
Headache, muscle
ache, backache, fever,
and arthritis menstrual
cramps .
Acetaminophen 650 mg PO May be harmful for people with
kidney or liver disease or those
who drink alcohol heavily
Headache, muscle
ache, backache, fever,
and arthritis.
Ibuprofen 400 mg PO May be harmful for people with
kidney or liver disease, asthma,
bleeding disorders, or those who
drink alcohol heavily.
Headache, muscle
ache, fever, sprains,
menstrual cramps,
backache, and arthritis
pain.
Naproxen 250-500 mg
PO
Not recommended for children
without a health care
professional’s supervision Cardio
vascular risks and G.I toxicity
Headache, muscle
ache, fever, menstrual
cramps, backache,
arthritis pain and
inflammation.

53. Drugs Dosages Adverse effects uses
Celecoxib 100-200 mg PO Generally well-
tolerated
Muscle aches, joint
pain, arthritis, pain
and inflammation
Ketorolac 15-60 IM/IV May be harmful for
people with kidney
or liver disease or
those who drink
alcohol heavily.
Not recommended
for children
Headache, muscle
ache, fever,
menstrual cramps,
cold or flu aches

54. OPIOIDS
 Most potent analgesics
 It produces analgesia by activating pain-inhibitory neurons
and directly inhibit pain-transmission neurons.
 Modes of delivery:
 Oral
 IV and IM
 Nasal spray
 Transdermal & transmucosal patch
 Sublingual route
 Suppository
 Epidural & Intrathecal route

55. Short acting opiods
Peak effect - 1–2 hrs
Duration – 4 hrs
Uses
 Acute pain - in moderate to severe chronic pain.
 Rescue medication for break through pain.
Eg –
 Codeine( 30- 60 mg PO QID)
 Tramadol (50- 100 mg PO QID)
 Morphine( 30 mg PO QID , 5 mg 4 hourly IV)

56. Long acting opiods
Steady pain relief for 12 hours.
Used for chronic pain.
Eg-
 Hydromorphone(2-4 mg PO QID)
 Methadone(5-20 mg PO/IV TDS)
 Buprenorphine
 Fentanyl( 25-100 µg/hour transdermal patch for 72
hour)
 Oxy codone(5-10 mg POQID)

57. What Dose to Give an Opioid Naïve
Patient?
 For opioid naïve start at a morphine equivalent of 2 to 5
mg IV or 10 mg PO
 Dose escalation should be more than 30 to 50% of base
dose to observe a meaningful change.
 Frequency of parenteral dosing can be as often as every
15 to 30 minutes until adequate analgesia is achieved

58. Opiod Analgesic Usual Starting
DoseDrug Equianalgesic
parenteral
dose
Starting iv
dose
iv:po ratio Starting dose
po
/transdermal
Duration of
Action
Morphine 10 mg Bolus
dose=0.05-0.1
mg /kg q 2-4
hours
Continuous
infusion=0.01-
0.04 mg/kg/hr
1:3 0.15-0.3
mg/kg/dose q
4 hours
3-4 hours
Hydromorphone 1.5 mg 0.015-0.02
mg/kg q 4
1:5 0.06 mg/kg q 3
to 4 hours
2-4 hours
Oxycodone 5-10 mg N/A 0.1-0.2 mg/kg
q 3 to 4
3-4 hours
Fentanyl 100mcg 1 to 2
mcg/kg/hr as
continuous
infusion
25 mcg
patch/hour
72 hours
Methadone 10 mg 0.1 mg/kg q 4
to 8 hours
1:2 0.2 mg/kgq 4
to 8 hours
12 to 150
hours

59.  Opioid-responsiveness – It is the ability to achieve pain relief
with evidence of improved function without the
development of unmanageable or intolerable side effects.
 Addiction-
1. Compulsive use and preoccupation with the drug and
its supply.
2. Inability to consistently Control the quantity used.
3. Craving the psychological effects of the drug.
4. Continued use despite adverse effects from the drug.

60.  Physical dependence - manifested by a withdrawal syndrome
which includes
 Sleeplessness -
 Anxiety and agitation – Anxiolytics
 Stomach cramps - Dicyclomine
 Body aches (flu-like symptoms) - Anti-inflammatory pain relievers
 Muscle cramps - Muscle relaxants
 Nausea, vomiting, diarrhea, sweating and skin crawling
 Alternative opioids - during detoxification.
 Methadone
 Buprenorphine decrease by 10-20 % per week.
 Tramadol

61. Therapeutic monitoring
Four A’s:
 Analgesia (pain relief – often measured by a
10-point rating scale).
 Activities of daily living (physical, psychological,
and social functioning).
 Adverse effects.
 Aberrant or abnormal drug-related behaviors.

62.  Is the person’s day centered around taking medication?
 Does the person take pain medication only on
occasion, perhaps three or four times per week?
 Have there been any other chemical (alcohol or drug)
abuse problems in the person’s life?
 Does the person in pain spend most of the day
resting, avoiding activity, or feeling depressed?
 Is the person in pain able to function (work, household
chores, and play) with pain medication in a way that is clearly
better than without?

64. Three Complications of Chronic High Dose
Opioid Therapy
1. Neurotoxicity
2. Tolerance
3. Opioid Induced Hyperalgesia
 Tolerance
Due to prolonged use of opiates
It occurs when there is a progressive lack of response
to a drug requiring increased dosing
Higher doses of opiates are required to elicit same
amount of analgesia

65. Opioid-induced Neurotoxicity
 Mediated through non-opioidergic mechanisms
 Due to neuro-excitatory metabolites of opioids
(morphine-6-glucuronide, oxymorphone-3-glucuronide)
 Causes spectrum of symptoms ranging from mild
confusion or drowsiness to hallucinations, delirium and
seizures
 Typically develops on initiation to a week of initiating an
opioid or reaching a dose that causes metabolite buildup.

66. Opioid Induced Hyperalgesia
 Clinical features- Hyperalgesia, allodynia,Myoclonus,
Confusion etc..
 Related to but different from tolerance
 Different from opioid neurotoxicity
 Has been observed and documented in literature since
19th century (Observed by Albutt in 1870)
 Treatment – dose reduction, Utilize NMDA antagonists,
Interventional pain techniques or neurosurgical
procedures

67. Anti Depressants
 Tricyclic anti depressants:
 Amitriptyline (25- 300 mg PO)
 Imipramine (75-400 mg PO)
 Desipramine (50- 300 mg PO)
 Nortriptyline (40- 150 mg PO)
 Adverse effects- Dry mouth, Blurred vision, Constipation,
Difficulty urinating , Worsening of glaucoma, Palpitations, Wt
gain and hypotension.

68. SSRIs(Selective Serotonin reuptake Inhibitors
Examples
 Fluoxetine
 Sertraline
 Citalopram
 Escitalopram
 Fewer side effects and are less sedating than TCAs.
 Effective for prevention of migraine but less effective for
other types of pain.

69. SNRIs
 Selective Serotonin and Nor-adrenaline Reptake
Inhibitors
Duloxetine (30- 60 mgPO)
Venlafaxine (75-400 mg PO)
Milnacipran(25-100 mg PO)
Serotonin syndrome.
 Antidepressant medications included in this warning are
fluoxetine, sertraline, paroxetine, escitalopram ,
duloxetine, milnacipran, and venlafaxine.
 Migraine drugs include Triptans.

70. ANTI CONVULSANT DRUGS
Gabapentin ( 600-1200 mg PO) Neuralgia
Pregabalin (150- 600 mg PO) Postherpetic neuralgia, diabetic
neuropathy, and fibromyalgia
Carbamazepine (200- 300 mg PO QID) Trigeminal neuralgia
Valproic acid (400- 600 mg PO OD) Prophylaxis of migraine
Lacosamide (100 mg PO BD) Diabetic neuropathic pain
Topiramate (25- 200 mg PO OD) Prophylaxis of migraine

71. SODIUM CHANNEL BLOCKING & ORAL ANTI-
ARRHYTHMIC AGENTS
 Drugs commonly used are
1. Lidocaine
2. Flecainide
3. Mexilitine
 Lidocaine has anti-arrhythmics with local anesthetic
properties and it is occasionally used in refractory pain.
 These drugs interrupt premature firing of damaged nerves
hence less capability of the nerve to trigger pain.

72. TOPICAL PAIN RELIEVERS
 Topical agents work locally and must be applied directly
over the painful area
 Transdermal drugs have effects throughout the body and
work when applied away from the area of pain
 Transdermal medication in a patch is absorbed through
the skin by the bloodstream over a period of time.
 Eg –
EMLA(Eutectic Mixture of Local Anesthetic; contains lidocaine and
prilocaine)
L.M.X.4 (contains lidocaine 4%),
 Used primarily prior to painful procedures such as while
lumbar puncture (spinal tap), and wart removal.

73. DRUGS USED AS MUSCLE RELAXANTS IN
CHRONIC PAIN
 Carisoprodol (200 mg PO BD)
 Metaxalone (800 mg PO TDS)
 Chlorzoxazone (250 – 750 mg PO TDS)
 Baclofen ( 5 mg PO TDS)
 Tizanidine (4 mg PO TDS)

74. Botulinum toxins
 Botulinum toxins have been found to be effective in
decreasing tone in overactive (hypertonic) muscles
 It is used for the treatment of the postural
abnormalities and pain associated with dystonias . Ex-
torticollis .
 Onabotulinumtoxin A is additionally approved by FDA to
prevent headaches in adults with chronic migraine

75. Interventional therapy
1. Intra articular steroid injections
2. Viscosupplementation
3. Spinal cord stimulation
4. Implanted targeted intra thecal drug delivery
5. Epidural analgesia
6. Nerve plexus block

76. Spinal cord stimulation:
Chronic radicular pain
 CRPS type I and II
 Painful peripheral neuropathies
 Peripheral vascular disease not amenable to
Surgical by pass or conventional therapy.
 Central pain
 Phantomb limb pain.

77. Patient control analgesia:
Indications:
 Post operative pain
management.
 Trauma
 Burns
 Sickle Cell Crisis

79. Epidural analgesia:
 Indication:
 Disk herniation, degeneration, and spondylosis
 Radiculopathy - cervical thoracic, lumbosacral
 Spinal stenosis and facet arthropathy
 Pelvic pain - Aid with pelvic floor physical therapy
 Labor epidural analgesia

81. TENS
 TENS is a method of treating pain that is non-invasive
and does not use pharmaceuticals.
 The TENS device sends impulses through the skin that
stimulate the nerve
 Indications:
Chronic post operative pain
Chronic post traumatic pain

83. Herbal Medications

84. Rules of thumb
 Use the lowest effective dose by the simplest route.
 Start with the simplest single agent and maximize it’s
potential before adding other drugs.
 Use scheduled, long-acting pain medications for
constant or frequent pain.
 Treat breakthrough pain with with parentral, short-
acting medication

85. Source of information
 Harrison 18th edition
 Bradley neurology
 ACPA guidelines for pain management
 WHO guidelines for pain management

86. “Pain is a more terrible lord of mankind than
death itself.”
Albert Schweitzer
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