1. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is mediated through peripheral sensory nerves and transmitted through the spinal cord and brain. 2. Pain can be classified based on its underlying mechanism as nociceptive, neuropathic, or mixed. Neuropathic pain occurs as a direct result of damage or dysfunction of the nervous system. 3. Pain is also classified based on duration as either acute pain, which resolves with healing, or chronic pain, which persists longer than 3 months and is associated with disability and mood changes. Chronic pain often requires a multidisciplinary treatment approach.

1. ALL ABOUT PAIN
Dr Ankur Sharma
MD Internal Medicine
Assistant Professor, Department of Medicine
L.N. Medical College and research Centre.

2. DEFINITION
The International Association for the Study of Pain (IASP) proposed the
following definition (1979): “Pain is an unpleasant sensory and
emotional
experience associated with actual or potential tissue damage
or described in terms of damage”.
It has been termed ‘the 5th vital sign’ and is mandated as
part of routine assessment of patients in hospital.

3. PAIN SENSORY SYSTEM
Peripheral Mechanism
Central Mechanism

4. PRIMARY AFFERENT NOCICEPTOR

5. Fast / First pain Slow /Second Pain
Fibres A C
Diameter
Myelination
Conduction velocity
2-5 m
Thinly
12 – 35 m/s
0.4 – 1.2 m
Unmyelinated
0.5 – 2 m/s
Neurotransmitter GLUTAMATE GLUTAMATE AND
SUBSTANCE P
(CGRP)

6. HARRISON PEARLS
• In normal individuals, the activity of A fibers does not produce
pain.
• A and C fibers innervate skin and deep somatic and visceral
structures. Some tissues, such as cornea are innervated only by
A and C fibers.
• The ability to detect painful stimuli is completely abolished
when conduction in A and C fibers axon is blocked.

7. SUBSTANTIA GELATINOSA

8. NOCICEPTORS AND THEIR STIMULI

9. • The transient receptor potential cation channel subfamily V
member 1 (TrpV1), also known as the vanilloid receptor,
mediates perception of some noxious stimuli, especially heat
sensations, by nociceptive neurons; it is activated by acidic pH,
endogenous mediators and by capsaicin, a component of hot
chili peppers.

10. SENSITIZATION
• When intense, repeated, or prolonged stimuli are applied to
damaged or inflamed tissues, the threshold for activating
primary afferent receptors is lowered and frequency of firing is
higher for all stimulus intensities.
• Mediators – BK, nerve-growth factor, prostaglandins and
leukotrienes.
• Centrally (dorsal horn of spinal cord) or Peripherally (at the
level of the peripheral nerve terminal).

11. CENTRAL PERIPHERAL
When activity, generated by
nociceptors during
inflammation, enhances the
excitability of nerve cells in the
dorsal horn of the spinal cord.
Increase in production,
transport, and membrane
insertion of chemically gated
and voltage-gated ion
channels.
ALLODYNIA – normally innocuous stimuli produces pain.
HYPERALGESIA – increases pain intensity in response to the same noxious

12. • Sensitization is particularly important for pain and tenderness
in deep tissues.
• Viscera are normally relatively insensitive to noxious stimuli,
although hollow viscera do generate significant discomfort
when distended.
• When inflamed, deep structures such as joints or hollow viscera
characteristically become exquisitely sensitive to mechanical
stimulation. (Pleuritic chest pain).
• A large proportion of afferents innervating viscera are
completely insensitive in normal non-injured, non inflamed
tissue, however, in the presence of inflammatory mediators,
these afferents become sensitive to mechanical stimuli – such
afferents have been termed as silent nociceptors.

13. NOCICEPTOR INDUCED INFLAMMATION

14. Primary activation Secondary activation
Cell damage – lowers pH, and
leads to release of K and
synthesis of PG’s and BK. PG
increase sensitivity of the nerve
terminal to BK and other pain
producing substances.
Impulses generated in the
stimulated terminal propagate
not only to the spinal cord but
also into the other terminal
branches where they induce the
release of peptides, including
substance P ( SP).
SP – 11 – amino acid peptide.
Functions – potent vasodilator, causes mast cell degranulation, is a chemoattractant for
and increases production of inflammatory mediators

15. CENTRAL MECHANISMS
Spinal cord and referred pain.
Ascending pathways of pain.

16. REFERRED PAIN
The axon of each primary afferent contacts many spinal neurons, and each spinal n
receives convergent inputs from many primary afferents.
The convergence of sensory inputs to a single spinal pain- transmission neuron is o
importance because it underlies the phenomenon of referred pain

18. ASCENDING PATHWAY FOR PAIN

19. Somatosensory cortex Frontal – insular cortex
Anterior cingulate gyrus
Sensory aspect of pain –
location, intensity and quality.
Emotional responses.

20. APPLIED ASPECT
Site of lesion Clinical presentation
Thalamic stroke “Dejerine – roussy syndrome”
Lesions in spinothalamic
pathway
Loss of pain and temperature
from opposite side of body.
Lesions in frontal lobe and
anterior cingulate gyri
Pain perception present but
emotional aspect is
diminished.

21. PAIN MODULATION
• The powerful affects of expectation and other psychological
variables on the intensity of pain is explained by brain circuits
that modulate the activity of the pain transmission pathways.
• Pain modulating circuits can enhance as well as suppress pain.
Both pain- inhibiting and pain-facilitating neurons in the
medulla project to and control spinal pain-transmission
neurons.

23. DESCENDING PATHWAY

25. MECHANISM OF PAIN MODULATION

27. CLASSIFICATION
Pain is commonly classified according to the following:
a) Aetiology and underlying condition
b) Mechanism
c) Duration

28. AETIOLOGY/UNDERLYING CONDITION
i. Trauma – an acute response to an injury.
ii. Surgery, Medical illness such as myocardial infarction or
appendicitis.
iii. Physiological conditions such as menstruation and labour.

29. MECHANISM
Inflammatory/Nociceptive – pain generated and maintained by
inflammatory mediators (such as prostaglandin E2), secondary to an
ongoing disease process. Examples include inflammatory arthritis or
mechanical back pain.
Neuropathic – Neuropathic pain is generated in malfunctioning nerves and
is defined as ‘pain arising as a direct consequence of a lesion or disease
affecting the somatosensory system’. This type of pain has special clinical
features as described below and may arise from injury or dysfunction of the
central or peripheral nervous system. Examples include painful diabetic
neuropathy and post-stroke pain.

30. Mixed pain – This includes features of both nociceptive and
neuropathic pain, such as back pain with radiculopathy (radiating
leg pain due to nerve irritation or compression).
Psychosomatic – Purely psychosomatic pain is
rare.However, pain, especially chronic pain, almost invariably has an
emotional and behavioural component.

32. NEUROPATHIC PAIN
Lesions of the peripheral and central nociceptive pathways
typically result in a loss or impairment of pain sensation.
Paradoxically, damage to or dysfunction of these pathways can
also result in pain.
Examples : Diabetic neuropathy , herpes zoster infection .
Often severe, and typically resistant to treatment.

33. Typically has an unusual burning, tingling, or electric shock like
quality and may occur spontaneously, or be triggered by very
light touch. – these features are rare in any other type of pain.
Associated with hyperalgesia (hyperpathia) and allodynia.
Sensory deficit is characteristically absent in the area of patient’s
pain.
Increased sensitivity and spontaneous activity – increased density
of sodium channels in the damaged nerve fibers.

34. SYMPATHETICALLY MEDIATED PAIN
Patients with peripheral nerve injury occasionally develop spontaneous
pain in the region innervated by the nerve.
The pain is often described as having a burning quality.
Typically begins after a delay of hours to days or even weeks and is
accompanied by swelling of the extremity, periarticular bone loss and
arthritic changes in the distal joints.
Damaged primary afferent nociceptors develop adrenergic sensitivity
and can be activated by stimulation of sympathetic outflow.

35. “Spontaneous pain + signs of sympathetic dysfunction” following
injury is termed as complex regional pain syndrome.
CRPS type I CRPS type II
Without obvious nerve injury
Other name
“Reflex sympathetic dystrophy”
Following identifiable nerve
injury
Other names
Post-traumatic neuralgia
If severe- causalgia.

36. ACUTE VS CHRONIC PAIN
Acute – most commonly a physiological response to an injury. It resolves with the
disappearance of a noxious stimulus or within the time frame of a normal healing
process.
Chronic – it can either be associated with an ongoing pathological process, such
as rheumatoid arthritis or malignancy, or be present for longer than is consistent
with a normal healing time. Pain is arbitrarily described as chronic if it persists for
longer than 3 months. Chronic pain is often associated with disability, mood and
sleep disturbance and a significant behavioural response. It is sometimes
subdivided into pain associated with cancer and pain associated with non-malignant
conditions.

37. CHRONIC PAIN
Depression is the most common emotional disturbance in patients with
chronic pain. Major depression is a common, treatable and potentially
fatal illness .
Other clues that a significant emotional disturbance is contributing to a
patients chronic pain complaint include pain that occurs multiple
unrelated sites, a pattern of recurrence, but separate, pain problems
beginning in childhood or adolescence; pain beginning at the time of
emotional trauma, such as loss of parent or spouse, history of physical
or sexual abuse, past or present substance abuse.

38. Chronic myofascial pain is very common, and, in these patients, deep palpa
reveal highly localized trigger points that are firm bands or knots in muscle
the pain following injection of local anesthetic into these trigger points sup
diagnosis .

39. Two key questions should be considered when dealing with a patient
in pain:
1. Is the pain a symptom of ongoing tissue damage or of another
condition that needs to be dealt with by another medical
professional?
2. What is the optimal treatment strategy: to either abolish the pain
altogether or reduce it to a more bearable level?

40. GENETICS
“Both congenital insensitivity to pain and extreme sensitivity to pain
(paroxysmal extreme pain disorder and erythromelalgia) are rare
genetic conditions which are disabling and shorten life span,
highlighting the importance of pain to our welfare and survival”

41. CLINICAL EVALUATION
Include a neurological examination looking at dermatomal sensory
dysfunction (suggesting radiculopathy) and particular tests (depending on
the region of the spine) to detect signs of nerve root irritation using stretch
tests such as
Lasègue’s test (or straight leg raising test) for low back pain; and
for the neck, the Spurling test (turning the patient’s head to the affected
side while extending and applying downward pressure to the top of the
patient’s head – a positive test is indicated by pain arising in the neck
radiating in the direction of the ipsilateral cor-responding dermatome).

42. MEASUREMENT OF PAIN
The most common of these scales is the Visual Analogue Scale (VAS): the patient
is given a horizontal line 10 cm long with ‘no pain’ on the left-hand side and ‘worst
possible pain’ on the right and is asked to mark the line according to the severity of the
pain.
Numerical rating scale: the patient is asked to assign a number from 0 to 10 to his
pain, 0 being no pain at all and 10 being the worst imaginable pain.
Verbal rating scale the patient rates his pain into one of the following
categories: none, mild, moderate or severe.

43. PAIN ASSESSMENT QUESTIONNAIRE
McGill Questionnaire assesses various aspects of pain, including
sensory qualities of pain, affective qualities (tension, fear etc.) and
has evaluative words that describe the subjective intensity of the total
pain experienced.
To assess for neuropathic pain, recently introduced
and validated tools such as the ‘painDETECT’ and ‘LANSS’
questionnaires are used to look for specific features pertaining to
neuropathic pain.

45. TREATMENT OF PAIN
• Acute pain
• Chronic pain
• Neuropathic pain

46. ASPIRIN, ACETAMINOPHEN, NSAIDS.
All these inhibit COX, and except for acetaminophen, all have
anti inflammatory actions, especially at higher doses.
Side-effects – Gastritis, nephrotoxicity, hepatoxicity with
acetaminophen at higher doses.
“NSAIDs can also increase blood pressure on long term hence
follow-up and treatment if necessary”.

47. COX ENZYMES
COX 1 COX 2
Homeostatic Inducible – in
inflammation
Advantages of selective COX 2 inhibitors (celecoxib)
Less gastric irritation
No benefit in terms of nephrotoxicity
They do not affect blood coagulation hence can be used
postoperatively.
Problems of selective COX 2 inhibitors
Cardiovascular – MI, stroke, thromboembolism, heart failure.

48. OPIOIDS
Most potent pain-relieving drugs.
Side effects – nausea, vomiting , constipation , pruritis – mostly
reversible.
Respiratory depression can be life-threatening.
Reversal agent – naloxone.

49. Name Comments
Codeine
Oxycodone
Morphine
Morphine SR Oral slow release preparation
Hydromorphone
Meperidine Toxic metabolite – normeripidine (accumulated in renal
failure) – hyperexcitability and seizures – not reversed by
naloxone .
Butorphanol Intranasal spray
Fentanyl Transdermal patch
Buprenorphine Transdermal patch
Tramadol Mixed opioid/ adrenergic action
Methadone Long half life, respiratory depression and sedation can
persist after analgesic effect subsides.

50. PATIENT CONTROLLED ANALGESIA
PCA uses a microprocessor controlled infusion device that can
deliver a baseline continuous dose of an opioid drug as well as
preprogrammed additional doses whenever patient pushes a
button. The patient can titrate dose to a the optimal level.
Safety guards
1. Lockout period after each demand dose is delivered
2. Limit on the total dose delivered per hour.

51. SPINAL CATHETER – SUBARACHNOID/
EPIDURAL
• Advantage – regional anesthesia can be obtained at relatively low doses.
• Used extensively during labour and delivery and for postoperative pain r
post-op

52. PERIPHERALLY ACTING OPIOID
ANTAGONIST
Recent advances for treating peripheral side effects
• Alvimopan
• Methylnaltrexone.

53. TCA, SSRI, SNRI.
Efficacy – TCA > SSRI
Safety – SSRI > TCA.
Side effects of TCA – orthostatic hypotension, drowsiness,
memory impairment, cardiac conduction defects, constipation,
and urinary retention.
SNRI = Efficacy of TCA + Safety of SSRI.

54. ANTICONVULSANTS AND
ANTIARRHYTHMICS
Phenytoin (Dilantin) and carbamazepine (Tegretol) – first shown
to relieve pain in trigeminal neuralgia.
Newer anticonvulsants – calcium channel alpha-2-delta subunit
ligands gabapentin (Neurontin) and pregabalin (Lyrica), effective
in various neuropathic pain.