PATHOPHYSIOLOGY AND ASSESSMENT OF

PAIN

Presenter: Dr. Priya S Nair

Moderator : Dr. Santosh. A
INTRODUCTION

 Pain is a complex phenomenon that includes both sensory-discriminative and

motivational-affective components.

 The sensory-discriminative component of pain depends on ascending

projections of tracts to the cerebral cortex. Sensory processing at these higher
levels results in the perception of the quality, location and intensity of the pain.

 The motivational-affective responses to painful stimuli include attention and

arousal, somatic and autonomic reflexes, endocrine responses, and emotional
changes.
 The International Association for the Study of Pain defines pain as an
unpleasant sensory and emotional experience associated with actual or
potential tissue damage, or described in terms of such damage.

 The term nociception is derived from noci and is used to describe neural
responses to traumatic or noxious stimuli.
 ANATOMY AND PHYSIOLOGY OF NOCICEPTION
 Pain is conducted along three neuronal pathways that transmit noxious stimuli from the
periphery to the cerebral cortex .

 First-order neurons send the proximal end of their axons into the spinal cord via the
dorsal (sensory) spinal root

 In the dorsal horn, the primary afferent neuron synapses with a second-order neuron
whose axon crosses the midline and ascends in the contralateral spinothalamic tract to
reach the thalamus. Second-order neurons synapse in thalamic nuclei with third-order
neurons, which then send projections through the internal capsule and corona radiata to
the postcentral gyrus of the cerebral cortex
 Second-order neurons are either nociceptive-specific or wide dynamic range (WDR)
neurons. Nociceptive-specific neurons serve only noxious stimuli, but WDR neurons
also receive nonnoxious afferent input from Aβ, Aδ, and C fibers.

 Nociceptive-specific neurons are arranged somatotopically in lamina I and have

discrete, somatic receptive fields; they are normally silent and respond only to high-
threshold noxious stimulation.

 WDR neurons are the most prevalent cell type in the dorsal horn. During repeated
stimulation, WDR neurons characteristically increase their firing rate exponentially in a
graded fashion (wind-up), even with the same stimulus intensity
Alternate Pain Pathways
Spinoreticular Tract mediate arousal and autonomic responses to pain.
Spinomesencephalic tract activates antinociceptive, descending pathways, because it
has some projections to the periaqueductal gray.
Spinohypothalamic and Spinotelencephalic tracts activate the hypothalamus and evoke
emotional behavior.
Spinocervical tract ascends uncrossed to the lateral cervical nucleus, which relays the
fibers to the contralateral thalamus.
Integration with the Sympathetic and Motor Systems

 Afferent dorsal horn neurons synapse both directly and indirectly with anterior
horn motor neurons.

 These synapses are responsible for the reflex muscle activity that is associated
with pain. Synapses between afferent nociceptive neurons and sympathetic
neurons in the intermediolateral column result in reflex sympathetically mediated
vasoconstriction, smooth muscle spasm, and the release of catecholamines,
both locally and from the adrenal medulla.
 Neurobiology of pain

 Transduction - noxious stimulus is converted to an electrical impulse in sensory

nerve endings.

 Transmission - conduction of electrical impulses to the CNS .

 Modulation - process of altering pain transmission. Both inhibitory and excitatory

mechanisms modulate pain impulse transmission in the PNS and CNS.

 Pain perception is mediated through the thalamus

 PHYSIOLOGY OF NOCICEPTION
 Nociceptors are characterized by a high threshold for activation and encode the
intensity of stimulation by increasing their discharge rates in a graded fashion.
Following repeated stimulation, they characteristically display delayed adaptation,
sensitization, and after discharges.

 Noxious sensations can often be broken down into two components: a fast, sharp, and
well-localized sensation and a slower onset, duller, and often poorly localized sensation

 Well-localized epicritic sensation is transduced by specialized end organs on the

afferent neuron and less well-localized protopathic sensation is transduced by free
nerve endings nociceptors that sense heat and mechanical and chemical tissue
damage.
Nociceptor types :1) mechanonociceptors- respond to pinch and pinprick

2) silent nociceptors - respond in the presence of inflammation

3) polymodal mechanoheat nociceptors - are most prevalent and respond to excessive

pressure, extremes of temperature and noxious substances such as bradykinin,
histamine, serotonin, H+, K+, some prostaglandins, capsaicin, and possibly adenosine
triphosphate.

At least two nociceptor receptors have been identified, TRPV1 and TRPV2.
Cutaneous Nociceptors
Somatic nociceptors include those in skin and in deep tissue.

Deep Somatic Nociceptors

Sensitized by inflammation. The pain arising from them is characteristically dull and
poorly localized. Specific nociceptors exist in muscles and joint capsules, and they
respond to mechanical, thermal, and chemical stimuli
Visceral Nociceptors
Visceral organs are generally insensitive tissues that mostly contain silent
nociceptors.

 Some organs are innervated by polymodal nociceptors that respond to smooth

muscle spasm, ischemia, and inflammation.

 The brain lack nociceptors however, the brain’s meningeal coverings do contain
nociceptors.

 Nociceptive C fibers from the esophagus, larynx, and trachea travel with the vagus
nerve to enter the nucleus solitarius in the brainstem. Afferent pain fibers from the
bladder, prostate, rectum, cervix and urethra, and genitalia are transmitted into the
spinal cord via parasympathetic nerves at the level of the S2–S4 nerve roots.
Chemical Mediators of Pain
 The most important peptides are substance P and calcitonin gene related peptide
(CGRP). Glutamate is the most important excitatory amino acid.

 Substance P sensitizes nociceptors, degranulates histamine from mast cells and 5-

HT from platelets, and is a potent vasodilator and chemoattractant for leukocytes.

 Substance P–releasing neurons also innervate the viscera and send collateral
fibers to paravertebral sympathetic ganglia; intense stimulation of viscera, therefore,
can cause direct postganglionic sympathetic discharge
Modulation of Pain
 Modulation of pain occurs peripherally at the nociceptor, in the spinal cord, and in
supraspinal structures. This modulation can either inhibit (suppress) or facilitate
(intensify) pain.

 Peripheral Modulation of Pain :Nociceptors and their neurons display sensitization

following repeated stimulation. Sensitization may be manifested as an enhanced
response to noxious stimulation or a newly acquired responsiveness to a wider range
of stimuli, including nonnoxious stimuli.

 Primary Hyperalgesia: Hyperalgesia at the original site of injury.Sensitization of

nociceptors results in a decrease in threshold, an increase in the frequency response
to the same stimulus intensity, a decrease in response latency, and spontaneous
firing even after cessation of the stimulus
 Commonly occurs with injury and following application of heat and is mediated
by the release of noxious substances from damaged tissues.

 Histamine is released from mast cells, basophils, and platelets, whereas

serotonin is released from mast cells and platelets. Bradykinin is released from
tissues following activation of factor XII.

 Following tissue damage phospholipase A2 acts on phospholipids released from

cell membranes to form arachidonic acid . The cyclooxygenase (COX) pathway
then converts the it into endoperoxides, which are then transformed into
prostacyclin, prostaglandins and thromboxanes. The lipoxygenase pathway
converts arachidonic acid into hydroperoxyl compounds, which are subsequently
converted into leukotrienes.
Acetylsalicylic acid (aspirin) and nonsteroidal antiinflammatory drugs produce
analgesia by inhibition of COX. The analgesic effect of corticosteroids is likely the
result of inhibition of prostaglandin production through blockade of phospholipase
A2 activation.
Secondary Hyperalgesia

 Secondary hyperalgesia is primarily due to antidromic release of substance P.

Substance P degranulates histamine and 5-HT, vasodilates blood vessels, causes
tissue edema, and induces the formation of leukotrienes
Central Modulation of Pain Facilitation

 Mechanisms responsible for central sensitization in the spinal cord:

1. Wind-up and sensitization of second-order neurons. WDR neurons increase their
frequency of discharge with the same repetitive stimuli and exhibit prolonged discharge,
even after afferent C fiber input has stopped.
2. Receptive field expansion. Dorsal horn neurons increase their receptive fields such
that adjacent neurons become responsive to stimuli (whether noxious or not) to which
they were previously unresponsive.
3. Hyperexcitability of flexion reflexes.
 Neurochemical mediators of central sensitization include substance P, CGRP, excitatory
amino acids l-glutamate and l-aspartate which trigger changes in membrane excitability
by interacting with G protein–coupled membrane receptors on neurons.

 Glutamate and aspartate play important roles in wind-up, via activation of N-methyl-d-
aspartate(NMDA) and other receptor mechanisms, and in the induction and
maintenance of central sensitization. Activation of NMDA receptors also induces nitric
oxide synthetase, increasing formation of nitric oxide. Both prostaglandins and nitric
oxide facilitate the release of excitatory amino acids in the spinal cord.
 Inhibition
Transmission of nociceptive input in the spinal cord can be inhibited by segmental
activity in the cord itself, as well as by descending neural activity from supraspinal
centers.
Segmental inhibition—Activation of large afferent fibers subserving sensation
inhibits WDR neuron and spinothalamic tract activity. Activation of noxious stimuli in
noncontiguous parts of the body inhibits WDR neurons at other levels, which may
explain why pain in one part of the body inhibits pain in other parts. These two
phenomena support a “gate” theory for pain processing in the spinal cord as initially
hypothesized by Melzack and Wall.
 Glycine and γ-aminobutyric acid (GABA) are amino acids that function as
inhibitory neurotransmitters and likely play an important role in segmental
inhibition of pain in the spinal cord. Antagonism of glycine and GABA results in
powerful facilitation of WDR neurons and produces allodynia and hyperesthesia.
 Adenosine also modulates nociceptive activity in the dorsal horn. The A1 receptor
mediates adenosine’s antinociceptive action
Gate Theory
The gate control theory of pain first proposed by Ronald Melzack and Patrick
Wall in 1965 to illustrate the neuronal network underlying pain modulation in the
spinal dorsal horn.
Painful information is projected to the supraspinal brain regions if the gate is
open, whereas painful stimulus is not felt if the gate is closed by the
simultaneous inhibitory impulses .
 Supraspinal inhibition—Supraspinal structures send fibers down the spinal cord to
inhibit pain in the dorsal horn.

 Important sites of origin for these descending pathways include the periaqueductal
gray, reticular formation, and nucleus raphe magnus (NRM).

 The endogenous opiate system (primarily the NRM and reticular formation) acts via
methionine enkephalin, leucine enkephalin, and β-endorphin. These opioids act
presynaptically to hyperpolarize primary afferent neurons and inhibit the release of
substance P; they also appear to cause some postsynaptic inhibition. Exogenous
opioids preferentially act postsynaptically on the second-order neurons or
interneurons in the substantia gelatinosa.
CLASSIFICATION
Clinically :acute pain
chronic pain( psychological and behavioral factors often play a major role)

Pathophysiology :Nociceptive (activation or sensitization of peripheral nociceptors,

specialized receptors that transduce noxious stimuli)

Neuropathic pain (result of injury or acquired abnormalities of

peripheral or central neural structures )
Etiology
Affected area
ACUTE PAIN
 Caused by noxious stimulation due to injury, a disease process, or the abnormal
function of muscle or viscera. It is nociceptive in nature.

 Most common forms are posttraumatic, postoperative, and obstetric pain ,pain
associated with acute medical illnesses

 As the tissue heals, the acute sensitization in the region surrounding the injury
gradually subsides, and sensory thresholds revert to normal

 They are self-limited or resolve with treatment in a few days or weeks.

 Two types of acute pain :Somatic pain—classified as superficial or deep.

 Superficial somatic pain is due to nociceptive input from skin, subcutaneous tissues,
and mucous membranes. It is characteristically well-localized and described as
sharp, pricking, throbbing, or burning sensation

 Deep somatic pain arises from muscles, tendons, joints, or bones. It has a dull,
aching quality and is less well localized.

 Visceral pain—caused by a disease process or abnormal function involving an

internal organ or its covering.

 Classified as: 1) true localized visceral pain 2) localized parietal pain 3) referred
visceral pain 4) referred parietal pain.
 True visceral pain is dull and diffuse and is associated with abnormal sympathetic
or parasympathetic activity causing nausea, vomiting, sweating, and changes in
blood pressure and heart rate.

 Parietal pain is a sharp pain described as a stabbing sensation that is localized to

the area around the organ or referred to a distant site.

 The phenomenon of visceral or parietal pain referred to cutaneous areas results

from patterns of embryological development and migration of tissues, and the
convergence of visceral and somatic afferent input into the central nervous system.
 Spinal visceral afferent fibers have their cell bodies in dorsal root ganglia (DRG) and
terminate in the spinal dorsal horn and delivers the visceral sensory information
through the contralateral spinothalamic tract or ipsilateral dorsal column to
supraspinal brain sites.

 Vagus nerve has cell bodies in the nodose ganglion and central terminals in the
nucleus tractus solitarii conveys pain information from organs in thoracic and
abdominal cavities. Hence involved in the prominent autonomic and emotional
reactions in visceral diseases associated with pain .
Embryologic Origin and Localization of Pain
The position in the spinal cord to which visceral afferent fibers pass for each organ
depends on the segment of the body from which the organ developed
embryologically.
Chronic pain
 Pain that persists after all tissue healing appears to be complete and extends beyond
the expected period of healing, typically 1 to 6 months

 Pain receptors continue to fire, even in the absence of tissue damage.

 Chronic pain may be nociceptive, neuropathic, or mixed, and psychological

mechanisms or environmental factors frequently play a major role.

 Patients with chronic pain often have attenuated or absent neuroendocrine stress
responses and have prominent sleep and affective mood disturbances.

 Neuropathic pain is classically paroxysmal and has a burning quality, and is

associated with hyperpathia. When it is also associated with loss of sensory input into
the central nervous system, it is termed deafferentation pain.
 Sensitization of peripheral and central nocisponsive neurons underlies the
neurobiologic basis of the transition from acute to chronic pain, whereas the
psychologic response after injury as well as noxious stimuli–induced modification in
the PNS and CNS is involved in the induction and maintenance of chronic pain

 Common forms of chronic pain include those associated with musculoskeletal

disorders, chronic visceral disorders, lesions of peripheral nerves, nerve roots, or
dorsal root ganglia , lesions of the central nervous system, and cancer pain.

 The pain of most musculoskeletal disorders (eg, rheumatoid arthritis and osteoarthritis)
is primarily nociceptive, whereas pain associated with peripheral or central neural
disorders is primarily neuropathic. The pain associated with some disorders, eg,
cancer and chronic back pain is often mixed.
 PATHOPHYSIOLOGY OF CHRONIC PAIN

 Chronic pain may be caused by a combination of peripheral, central, and

psychological mechanisms. Sensitization of nociceptors plays a major role in the
origin of pain associated with peripheral mechanisms, such as chronic musculoskeletal
and visceral disorders.

 Neuropathic pain involves peripheral–central and central neural mechanisms that are
complex and generally associated with partial or complete lesions of peripheral nerves,
dorsal root ganglia, nerve roots, or more central structures.

 Peripheral mechanisms include spontaneous discharges, sensitization of receptors (to

mechanical, thermal, and chemical stimuli), and upregulation of adrenergic receptors.
 Central mechanisms include loss of segmental inhibition, wind-up of WDR neurons,
spontaneous discharges in deafferentated neurons, and reorganization of neural
connections.

 The sympathetic nervous system appears to play a major role in some patients with
chronic pain. Painful disorders that often respond to sympathetic blocks include
complex regional pain syndrome, deafferentation syndromes due to nerve avulsion or
amputations, and postherpetic neuralgia.
Neuropathic Pain
 Neuropathic pain is pain that persists after tissue injury has healed and is
characterized by reduced sensory and nociceptive thresholds (allodynia and
hyperalgesia)

 Injury of peripheral nerves by trauma, surgery, or diseases frequently results in the

development of neuropathic pain. It reflects a maladaptive function of a damaged pain
system.

 pathophysiology- a neuroinflammatory response following innate immune system

activation. After nerve injury occurs, it may form a “nerve-end neuroma.” Usually, the
ectopic firing generated in end bulb and sprouts within the neuroma, as well as the cell
bodies in DRG, significantly contribute to the nociceptive hypersensitivity and ectopic
Psychobiology of Pain

 Peripheral nociceptive information is delivered through spinoreticular pathways to

diencephalic and telencephalic structures, including the medial thalamus,
hypothalamus, amygdala, and limbic cortex.Central sensitization and adaptation of
synaptic plasticity occur in these brain regions and contribute to the induction and
maintenance of the emotional distress that often accompanies pain.

 Intrinsic interactions occur between the sensory and affective components of pain.
patients with chronic pain experience debilitating depression, anxiety, cognitive
deficits such as memory impairment, and other negative psychological components
of pain.

 Severe emotional distress can trigger new pain or exacerbate ongoing pain in the
patients with previous painful experiences.
Systemic Responses to Acute Pain
 Acute pain is typically associated with a systemic neuroendocrine stress response that is
proportional to pain intensity. The efferent limb is mediated by the sympathetic nervous and
endocrine systems. Sympathetic activation increases efferent sympathetic tone to all
viscera and releases catecholamines from the adrenal medulla.

Cardiovascular Effects

 Hypertension, tachycardia, enhanced myocardial irritability, and increased systemic

vascular resistance. Cardiac output increases in most normal patients but may decrease in
patients with compromised ventricular function. Because of the increase in myocardial

oxygen demand, pain can worsen or precipitate myocardial ischemia .

Respiratory Effects

 An increase in total body oxygen consumption and carbon dioxide production

necessitates a concomitant increase in minute ventilation. The latter increases the
work of breathing, particularly in patients with underlying lung disease.

 Pain due to abdominal or thoracic incisions further compromises pulmonary function

because of guarding. Decreased movement of the chest wall reduces tidal volume and
functional residual capacity, promoting atelectasis, intrapulmonary shunting,
hypoxemia, and, less commonly, hypoventilation. Reductions in vital capacity impair
coughing and clearing of secretion
Gastrointestinal and Urinary Effects

 Enhanced sympathetic tone increases sphincter tone and decreases intestinal and
urinary bladder motility, promoting ileus and urinary retention. Hypersecretion of gastric
acid can promote stress ulceration. Nausea, vomiting, and constipation are common.

Endocrine Effects

 Stress increases release of catabolic hormones (catecholamines, cortisol, and

glucagon) and inhibits release of anabolic hormones (insulin and testosterone).
Patients develop a negative nitrogen balance, carbohydrate intolerance, and increased
lipolysis. The increase in cortisol, renin, angiotensin, aldosterone, and antidiuretic
hormone results in sodium retention, water retention, and secondary expansion of the
extracellular space.
Hematological Effects

 The neuroendocrine stress response to acute pain may increase platelet

adhesiveness, reduce fibrinolysis, and promote a hypercoagulability state

Immune Effects

 The neuroendocrine stress response produces leukocytosis and may predispose

patients to infection. Worsening carbohydrate intolerance with sustained
hyperglycemia also increases the risk of infection.

Psychological Effects

 Anxiety and sleep disturbances are common reactions to acute pain. With prolonged
duration of the pain, depression is not unusual
Systemic Responses to Chronic Pain

The neuroendocrine stress response is generally observed only in patients with

severe recurring pain due to peripheral nociceptive mechanisms and in patients
with prominent central mechanisms such as pain associated with paraplegia. It is
attenuated or absent in most patients with chronic pain. Sleep and affective
disturbances, particularly depression, are often prominent. Many patients also
experience significant decreases or increases in appetite and psychological
stress related to social relationships.
Pain in Neonate and Infant
 Human fetus develops pain perception by 23 weeks of gestation. Postnatal maturity
of pain behavior develops quickly after birth.

 Newborns and young children have significantly lower pain thresholds and
exaggerated pain responses compared to adults. They have immature ability to
produce neurochemicals that inhibit pain.

 Toddlers and adolescents exhibit long-lasting hypersensitivity to painful stimuli after

painful experiences as neonates. These observations highlight the clinical
importance of optimal management of pain in neonates and infants.
Evaluation of pain in children is difficult as they are unable to express pain in suitable
words.
Indirect assessment can be done in neonates/infants by observing physiological and
behavioural changes.
ASSESSMENT OF PAIN

Information about location, onset, and quality of pain, as well as alleviating and
exacerbating factors, should be obtained, along with a pain history that includes previous
therapies and changes in symptoms over time.

In addition to physical symptoms, chronic pain usually involves a psychological component

that should be addressed.

Imaging studies such as plain radiographs, computed tomography (CT), magnetic

resonance imaging (MRI), and bone scans can often help delineate physiological cause .

Electromyography and nerve conduction studies complement one another and are useful
for confirming the diagnosis of entrapment syndromes, radicular syndromes, neural
trauma, and polyneuropathies.
 They can often distinguish between neurogenic and myogenic disorders. Patterns of
abnormalities can localize a lesion to the spinal cord, nerve root, limb plexus, or
peripheral nerve.

 Electromyography employs needle electrodes to record potentials in individual muscles.

Muscle potentials are recorded first while the muscle is at rest and then as the patient is
asked to move the muscle. Abnormalities in muscles produce changes in amplitude and
duration as well as polyphasic action potentials.

 Peripheral nerve conduction studies employ supramaximal stimulations of motor or

mixed sensorimotor nerve, whereas muscle potentials are recorded over the appropriate
muscle.
 Nerve conduction studies distinguish between mononeuropathies (due to trauma,
compression, or entrapment) and polyneuropathies
Pain intensity assessed by unidimensional and multidimensional methods
Psychosocial evaluation

 It is useful whenever medical evaluation fails to reveal an apparent cause for pain,
when pain intensity, characteristics, or duration are disproportionate to disease or
injury, or when psychological or social issues, or both, are apparent.
 These types of evaluations help clarify the role of behavioral factors.
 The most commonly used psychological tests are the Minnesota Multiphasic
Personality Inventory (MMPI) and Beck Depression Inventory. The MMPI is used
primarily to confirm clinical impressions about the role of psychological factors; it
cannot reliably distinguish between “organic” and “functional” pain. The Beck
Depression Inventory is a useful test for identifying patients with major depression.
 These include the Multidimensional Pain Inventory (MPI), Medical
Outcomes Survey 36-Item Short Form (SF-36), Pain Disability Index (PDI),
and Oswestry Disability Index (ODI). Emotional disorders are commonly
associated with complaints of chronic pain, and chronic pain often results in
varying degrees of psychological distress.
ASSESSMENT OF PAIN IN PRESCHOOL CHILDREN
PAIN ASSESSMENT IN SCHOOL AGED CHILDREN

VAS
Wong Baker Faces Pain Rating scale
Macgills pain questionaire
 REFERENCES

1. Miller’s Anesthesia 9th edition

2. Stoelting’s Pharmacology and Physiology in Anesthetic Practice
3. Morgan And Mikhail’s Clinical Anesthesiology 6th edition
4. Anesthesia Review For DNB students 2nd edition
THANK YOU