Subject:

Topic:
Lecturer:
Date:

Neurology II
2.07 Neurology of Pain
Dra. Pia Camara-Chua
August 24, 2015
OUTLINE

I. Pain
II. Anatomy and Physiology of Pain
III. Spinal Afferent Tracts for Pain
IV. Other Spinocerebral Afferent Tracts
V. Thalamic Terminus of Pain Fibers
VI. Physiologic Aspects of Pain
VII. Clinical and Physiologic Aspects of Pain
VIII. Approach to the Patient with Pain as the Predominant
Symptom

IX. Treatment of Intractable Pain

X. Supplemental Medication for the Treatment of Pain
XI. Treatment of Neuropathic Pain
XII. Treatment of Reflex Sympathetic Dystrophy
XIII. Ablative Surgery in the Treatment of Pain
XIV. Non-Medical Methods for the Treatment of Pain
XV. Appendix

OBJECTIVES
At the end of the lecture, the student should be able to:
1. No objectives were given.
2. But to study this Trans, we know it will be a bit dull and dry. But just know the key points in each heading as well as
remember important structures and pathways involved in neurology of pain.
3. It will be helpful if you know by heart the pathways of pain.
4. Also know treatment modalities for pain.
References: 2015B Trans, Dras .ppt, Adams Neurology

I. PAIN
Pain stands pre-eminent among all the sensory experiences by which humans judge the existence of disease within
themselves
o Pain is the most common symptom of disease
o Pain is one of the earliest signs of morbidity
Even if the main problem or disease does not manifest and is obvious, we experience this first.
The painful experiences of the sick pose problems in virtually every field of medicine
o Pain can have structural basis
o It can have an organic/underlying cause
o Pain can appear to have little or no structural basis
Migraine or trigeminal neuralgia
o Pain can be psychiatric
II. ANATOMY AND PHYSIOLOGY OF PAIN
A. Historical Perspective
2 major theories:
o Specificity Theory:
Von Frey
Skin consisted of a mosaic of discrete sensory spots that give rise to one sensation when stimulated such as
pain, pressure, warmth or cold
Example, on an area on the forearm, when a certain spot is stimulated would illicit sensation of pain, warmth
or coldness. These discrete sensory spots would have a corresponding sensation when triggered
Each sensation has a distinct end-organ in the skin and each stimulus-specific end organ is connected to its
own private pathway in the brain
o Pattern/Summation Theory:
Also known as Intensivity Theory
Goldscheider
Pressure spots could produce pain when sufficiently stimulated
There are no distinct pain receptors, but its the result of the summation of impulses such as the amount of
pressure/force or thermal stimuli applied to the skin that will elicit the corresponding stimulus
Sensation of pain is the result of impulses excited by pressure or thermal stimuli applied to the skin
Head et al., 1905
o Postulated the existence of 2 systems of cutaneous receptors and conducting systems
An ancient protopathic system
Sub-serving pain and extreme differences of temperature
Yielding ungraded diffuse impressions of an all-or-none type
More recently evolved epicritic system
Trans Group: Joebeth Tabora, Nico Talento, Pamela Tan, Paul Tan
Edited By: Joseph Sta. Ana and Joy Rahayel

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 Mediated touch, two-point discrimination and lesser differences of temperature, as well as

localized pain spinothalamic tract
The pain and hyperesthesia that follow damage to a peripheral nerve were attributed to a loss of
inhibition that was normally exerted by the epicritic upon the protopathic system
o Eventually lost credibility as findings could not be confirmed
Melzack and Wall,1965
o Gate control theory of pain
o Observed in decerebrate and spinal cats:
Peripheral stimulation of large myelinated fibers (A/A fibers) produced a (-) dorsal root potential
Stimulation of small (Unmyelinated) C (Pain) fibers caused a (+) positive root potential
These potentials which were a reflection of presynaptic inhibition or excitation, modulated the
activity of secondary transmitting neurons (T cells) in the dorsal horn and that this modulation was
mediated through inhibitory (I) cells.

Figure 1. The Gate control theory of pain.

Figure 2. Role of Interneurons. There are interneurons that exist in between pathways. When you stimulate
fibers, specific gates can open which will allow a stimulus to reach the brain thus pain would be felt.
(Stimulated) Large myelinated fibers -> Excite the I cells -> Presynaptic inhibition of the T cells -> Impulse
will not reach the brain -> No pain sensation (Close gate)
(Stimulated) Small pain fibers -> inhibit I cells -> Excitation of T cells -> Impulse reaches the brain -> Pain
is felt (Open gate)
Theory also gives emphasis that pain impulses from the dorsal horn must also be under the control of a
descending system of fibers from the brainstem, thalamus, and limbic lobes
Gate control theory lost credibility because proponents cannot confirm theory due to some inaccuracy.
However this is still described and rationalized in the general framework of the oldest theory, that of
specificity
B. Pain Receptors and Peripheral Afferent
Pathways
The sensory and motor fibers have been classified according to their size and function: (See Appendix)
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Figure 3. Classification and function of sensory peripheral nerve fiber types and symptoms associated with
intrinsic dysfunction of each type. Focus more on A-delta and C fibers.
It is now well-established that 2 types of afferent fibers in the distal axons of primary sensory neurons
respond maximally to nociceptive stimuli
o Very fine, unmyelinated, slowly conducting C fiber
o Thinly myelinated, more rapidly conducting A- (A-delta) fiber
Peripheral terminations of both these primary pain afferents or receptors are the free, profusely branched
nerve endings in the skin and other organs
o Covered by Schwann cells but contain little or no myelin

Table 1. 3 Broad Categories of Free-Ending Receptors.

Receptors

Stimulus

Fiber Type

Mechanorecept
ors

Activated by
mechanical
stimulation

A- fibers
C fibers

Thermorecepto
rs

Activated by
thermal
stimulation

C fibers

Polymodal
nociceptors

Activated by
noxious or tissuedamaging stimuli;
can respond to
mechanical and
thermal stimuli
Also responds to
chemical
mediators

Majority are C
fibers
Certain A- fibers
respond to light
touch,
temperature,
pressure and
pain

Majority of C-fibers are polymodal and are most effectively excited by noxious or tissue-damaging stimuli
o Painful stimuli are translated in to electrical depolarization in nerve endings are beginning to be
understood.
o When noxious stimuli activate a number of specialized molecules -> will open cationic channels in
membranes of nerve endings -> activates voltage gated sodium channels and generates an action
potential in the sensory axon.

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Figure 4. Spinal cord in traverse section. This illustrates the course of the afferent fibers and the major
descending pathways. Fast conducting pain fibers are not confined to the spinothalamic tract but are
scattered diffusely in the anterolateral funiculus.
o The peripheral afferent pain fibers of both A-delta and C fibers have their cell bodies in the dorsal root
ganglia (Interchangeable -> Dorsal horn = Posterior horn)
o Central extensions of these nerve cells project, via the dorsal root, to the dorsal horn of the spinal cord
The pain afferents, after travelling from the nerve endings, occupy mainly the lateral part of the root entry
zone

Figure 5. Traverse section through a cervical segment of the spinal cord. (This illustrates the subdivision of
the gray matter into laminae according to Rexed and the entry and termination of the main sensory fibers).

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Figure 6. Zona Terminalis or Tract of Lissauer.

Within the spinal cord, many of the C fibers form a discrete bundle called zona terminalis or the tract of
Lissauer
o Predominantly a pain pathway
o Also contains deep sensory or propriospinal fibers
C. Dermatomal Distribution of Pain Fibers
Each sensory unit is composed of:
o Sensory nerve cell in the DRG
o Central and peripheral extensions
o Cutaneous and visceral endings
Has a unique topography maintained throughout the sensory system from the periphery to the central
cortex
Discrete segmental distribution of sensory units permits the construction of sensory maps

Figure 7. Sensory Map. Each area is served by a specific unit.

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Figure 8. Topography of peripheral pathways and sensory levels.

o These areas of projection from visceral structures roughly correspond to the areas of adjacent root
innervations, with some exceptions because of routing of sensory nerves to organs that migrate with
development
D. Dorsal Horn
After traversing the tract of Lissauer, the afferent pain fibers terminate in the posterior gray matter or
dorsal horn
Reside predominantly in the marginal zone
Most fibers terminate within the segment of their entry into the cord
o For example, all T1 fibers terminate at the T1 level, T2 fibers on the T2 level but;
o Some extend ipsilateral to 1 or 2 adjacent rostral and caudal segments
For example, some T1 fibers will go up to C8-C7 or some would go down to T2-T3 but mostly will
terminate on the sensory level that is assigned to them
Some project to the contralateral dorsal horn via the anterior commissure but most of them will stay
ipsilaterally
The 2nd order neurons are the sites of synapse of afferent sensory fibers in the dorsal horn
Arranged in a series of 6 layers or laminae called the Rexed laminae

Figure 9. Rexed Lamina

Laminae I to IV:
o Concerned with exteroceptive sensations
Laminae V and VI:
o Concerned primarily with proprioceptive sensations
o They also respond to cutaneous stimuli
Lamina VII:
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o Acts as a relay between midbrain and cerebellum

Lamina VIII:
o Modulates motor activity, most probably via gamma motor neurons (Not the concern of our topic)
Lamina IX:
o Main motor area of the spinal cord
Lamina X:
o Surrounds the central canal

Figure 10. Rexed Laminae

Other cells that respond to cutaneous stimuli are located in Laminae VII and VIII
o The latter neurons are responsive to descending impulses from brainstem nuclei as well as segmental
sensory impulses
From these cells of termination, second order neurons connect with ventral and lateral horn cells in the
same and adjacent spinal segments and subserve both somatic and autonomic reflexes
The main bundle of secondary neurons subserving pain sensation projects contralaterally (Also
ipsilaterally) to higher levels
o Remember, once the second order neurons are there in the dorsal horn, most of the fibers cross
contralaterally and then ascend towards the brain. They ascend towards the level of sensory unit
and then they go up.
o Remember in the motor tract they cross at the level of the medulla but in spinothalamic tract, they
cross at the level where they enter.
E. Neurotransmitters
A- fibers
o Excitatory neurotransmitters
Glutamate
Aspartate
o Nucleotides
ATP
C fibers
o Substance P (Main NT and important in the management of pain)
Excites nociceptive dorsal root ganglion and dorsal horn neurons
Destruction produces analgesia
Taking away substance P, the patient is pain free.
Remember Substance P-ain
Opiates
o Important modulators of pain as they are relayed through the dorsal horn and through nuclei in the
medulla and midbrain
o Noted to decrease substance P in the spinal cord
o 3 types of opiate receptors:
Mu
Delta
Kappa
When activated, laminaI neurons release endogenous morphine-like peptides that bind specifically to
opiate receptors and inhibit pain transmission at the dorsal horn level
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o Enkephalins
o Endorphins make you happy
o Dynorphins
Since they are endogenous, when the body feels pain, the body produces these substances so that
without the use of external pain killers, the body would be able to relieve the pain.
III. SPINAL AFFERENT TRACTS FOR PAIN
A. Lateral Spinothalamic Tract
Axons of 2 neurons that subserve pain sensation originate in lamina I, II, V, VII and VIII of the spinal
gray matter
Principal bundle of axons decussates in the anterior commissure
Ascends in the anterolateral fasciculus of opposite side of the spinal cord as the spinothalamic tract to
terminate in several brainstem and thalamic structures
Axons carrying pain impulses from each dermatome decussate 1-3 segments above the level of root
entry
o Discrete lesion of the lateral spinal cord creates a loss of pain and thermal sensation of the
contralateral trunk
o The dermatomal level of which is two to three segments below that of the spinal cord lesion

Figure 11. Spinothalamic tract, the most important tract for pain.
As
o
o
o

the ascending fibers cross the cord, they are added to the inner side of the spinothalamic tract
The longest fibers from the sacral segments come to lie most superficially
Fibers from successively more rostral levels occupy progressively deeper positions
Provides an explanation for sacral sparing of pain and thermal sensation created by centrally placed
lesions of the spinal cord

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Figure 12. As the ascending fibers cross the cord, they are added to the inner side of the spinothalamic
tract.
IV. OTHER SPINOCEREBRAL AFFERENT TRACTS
A. Spinoreticulothalamic or Paleospinothalamic
Pathway
Projects directly to the reticular core of the medulla and midbrain
Then to the medial and intralaminar nuclei of the thalamus

Figure 13. The spinoreticulothalamic or paleospinothalamic pathway.

Spine reticular formation (midbrain) brainstem thalamus sensory cortex
More medially placed pathway in the anterolateral cord ascend to the brainstem reticular core via a series of
short interneuronal links
o Unclear whether these are collateral vs. independent system
B. Direct Spinothalamic Pathway in the
Anterolateral Fasciculus

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Figure 14. Direct spinothalamic pathway in the anterolateral fasciculus.

Figure 15. Pathways for visceral pain from the esophagus, stomach, small bowel and proximal colon are
carried largely in CN X and terminate in the nucleus of the solitary tract before projecting to the thalamus.

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Figure 16. Solitariothalamic tract.

V. THALAMIC TERMINUS OF PAIN FIBERS
Spinoreticulothalamic fibers project onto the medial intralaminar nuclei
Projections from the dorsal column nuclei
o Have a modulating influence on pain transmission
o Project to ventrobasal and ventroposterior group of nuclei
As the pathway ascends from peripheral nerve to spinal, medullary, mesencephalic, thalamic and limbic
levels, the predictability of neuron responsivity to noxious stimuli diminishes
The direct spinothalamic fibers separate into 2 bundles as they approach the thalamus:
o Lateral division

Terminates in the ventrobasal and posterior groups of nuclei

VPL nucleus
o Medial division

Terminates mainly in the intralaminar complex of nuclei and nucleus submedius

Figure 17. Parts of Thalamic Nuclei

A. Thalamocortical Projections
Ventrobasal and ventroposterior group of nuclei project to 2 main cortical areas:
o Primary sensory cortex
o Upper bank of the Sylvian fissure
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Concerned primarily with the reception of tactile and proprioceptive stimuli and all discriminative
sensory functions, including pain
The intralaminar nuclei:
o Project to the hypothalamus, amygdaloid nuclei and limbic cortex
o Probably mediate the arousal and affective aspects of pain and autonomic responses

Figure 18. Thalamic nuclei and its corresponding cortical map.

See appendix for larger picture.
The cortical representation in the sensory cortex correspond to the sensory homunculus
o Allows for the accurate localization of the site of origin of a painful stimulus

Figure 19. Somatosensory map, sensory homunculus.

System of descending fibers and way stations that modulate activity in nociceptive pathways
Endogenous pain control system
o Emanates from the frontal cortex and hypothalamus and projects to cells in the periaqueductal region
of the midbrain
o Passes to the ventromedial medulla
o Descends in the dorsal part of the lateral fasciculus of the spinal cord
o To lamina I, II, and V of the posterior horn
VI. PHYSIOLOGIC ASPECTS OF PAIN
The stimuli that activate pain receptors vary from one tissue to another
With damage to tissue, there is release of proteolytic enzymes
o Act locally on tissue proteins to liberate substances that excite peripheral nociceptors
o Ex. Histamine, prostaglandins, serotonin, K ions, kinins
Direct stimulation of nociceptors release polypeptide mediators that enhance pain perception
o Ex. Substance P

Released from nerve endings of C fibers in the skin during peripheral nerve stimulation

Causes erythema by dilating cutaneous vessels and edema by releasing histamine from mast cells;
also attracts chemoattractant for leukocytes

Called neurogenic inflammation

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A. Perception of Pain
Threshold for perception of pain
o Lowest intensity of a stimulus recognized as pain
o Approximately the same in all persons
Inflammation lowers the threshold for perception of pain by a process called sensitization
o Allows ordinarily innocuous stimuli to produce pain in sensitized tissues
Pain threshold is raised by:
o Local anesthetics
o Certain lesions of the nervous system
o Centrally acting analgesic drugs
Other mechanisms that alter the perception of pain:
o Placebo
o Acupuncture
o Distraction and suggestion
o Strong emotion
o Manic states
o Depression
o Anxiety
The conscious awareness or perception of pain occurs only when pain impulses reach the thalamocortical
level
Sensation, perception and the various conscious and unconscious responses to a pain stimulus comprise an
indivisible process
Cerebral cortex governs the patients reaction to pain
o Also likely that the cortex can suppress or modify the perception of pain
B. Endogenous Pain Control Mechanisms
Discovery of a neuronal analgesia system that can be activated by the administration of opiates or by
naturally occurring brain substances that share the properties of opiates
In humans, electrical stimulation of the following sites produce analgesia
o Midbrain periaqueductal gray matter
o Rostroventral medulla

Nucleus raphe magnus

Adjacent reticular formation

o Dorsolateral pontine tegmentum

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Figure 20. Descending Pathway Modulatory System.

Opiates also act pre and postsynaptically on the neurons of laminae I and V of the dorsal horn, suppressing
afferent pain impulses from both the A- and C fibers
o Effects can be reversed by naloxone (Narcotic antagonist)

Naloxone can enhance clinical pain and interferes with the pain relief produced by placebos
These observations (On opiates and naloxone) suggest that the mysterious, beneficial effect of placebos
(Also perhaps including acupuncture) may be a result of the activation of an endogenous system that shuts
off the pain through the release of pain-relieving endogenous opioids, or endorphins
o These are like the morphine within us
Activators of the endogenous pain control mechanisms
o Prolonged pain and fear most powerful
o Stressful conditions
Endorphins
o Endorphins are found in greatest concentration in relation to opiate receptors in the midbrain
o At the level of the spinal cord, exclusively enkephalin receptors are found

-endorphin

Enkephalin

Dynorphin

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Figure 21. Mechanism of action of encephalin (Endorphin) and morphine in the transmission of pain impulses from the
periphery to the CNS. Spinal interneurons containing enkephalin synapse with the terminals of pain fibers and inhibit the
release of the presumptive transmitter, substance P. As a result, the receptor neuron in the dorsal horn receives less
excitatory (Pain) impulses and transit fewer pain impulses to the brain. Morphine binds to unoccupied enkephalin receptors,
mimicking the pain-suppressing effects of the opiate enkephalin.

Descending pain-control systems contain noradrenergic and serotonergic, as well as opiate links
Descending norepinephrine-containing pathway
o From locus ceruleus in the dorsolateral pons to the spinal cord
o Activation blocks spinal nociceptive neurons
Rostroventral medulla contains a large number of serotonergic neurons from which descending fibers inhibit
dorsal horn cells concerned with pain transmission
o Providing rationale for the use of certain antidepressant medications (Serotonin agonists)
VII. CLINICAL AND PSYCHOLOGIC ASPECTS OF
PAIN
A. Terminology

Figure 22. Terms related to experience of altered sensations and pain. Please be familiar with them.

FROM 2015B:
Hyperesthesia is a general term for heightened cutaneous sensitivity
Hyperalgesia refers to an increased sensitivity and a lower threshold to painful stimuli
Hyperpathia is a demonstrable reduction in pain perception
(e.g. Elevated threshold) associated with an increased reaction to the stimulus once it is perceived.
o Although subtly different, Hyperpathia can be a type of hyperalgesia according to Dra. Chua.
Pallanesthesia - Loss of perception of vibration
o The mechanism of these abnormalities is not clear but both hyperpathia and allodynia are common
features of neuropathic or neurogenic pain (e.g. Pain generated by peripheral neuropathy )
These features are exemplified by causalgia, a special type of burning pain that results from
interruption of a peripheral nerve.
B. Skin Pain and Deep Sensibility
Two types of skin pain:
Pricking pain:
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o Fast pain
o Evoked immediately
o Transmitted by A- fibers
Stinging or burning pain:
o Slow pain
o Follows in a second or two
o Transmitted by C fibers
Both types of dermal pain can be localized
Constitute the double response of Lewis
o Because there are A- fibers and C fibers in the skin, there is initial pain with slow pain that persists
(Masakit na nga lalo pang sumakit)
Compression of nerves by the application of a tourniquet to a limb abolishes pricking pain before burning
pain because large fibers are more susceptible to pressure
Deep pain from visceral and skeletomuscular structures is basically aching in quality. (Cannot be localized,
but pain is present)
If intense can be sharp and penetrating (Knife-like)
o We are able to distinguish visceral pain, wherein one may not be able to localize the pain, from
cutaneous pain, which is easier to localize.
Visceral pain produces 2 additional sensations
o Referred Hyperalgesia
Tenderness at remote superficial sites
o Visceral Hyperalgesia
Enhanced pain sensitivity in the same and nearby organs
Because somatic and visceral sensibility may overlap (Overlap in sensory levels)
VISCERAL PAIN
Deep
Diffuse and poorly localized
Margins of the painful zone are not well
delineated
o Because of the relative paucity of nerve
endings in viscera compared to the skin

C. Referred pain
Deep pain has indefinite boundaries
o Location is distant from the visceral structure involved
o Tends to be referred not to the skin overlying the viscera but to other areas of skin innervated by the
spinal segment or segments
o Examples: There are times that chest pains (Myocardial infarction) have referred pain to shoulder and
jaw while patients with cholecystitis or gall bladder disease may have referred pain to right shoulder or
right upper back.
FROM 2015B:
Referred Pain:
Pain projected at a site distant from the source
o Example. Afferent fibers from cardiac structures (T1-T4)
Chest pain can go as far as the inner side of arm, because of T1-T4 involvement
o Take note: Small caliber pain afferents from deep structures project to a wide range of Lamina V
neurons in the dorsal horn, as do cutaneous afferents.
o This phenomenon can be further explained by the convergence of deep and cutaneous afferents
on the same dorsal horn cells, coupled with the fact that cutaneous afferents are more numerous
than visceral afferents and have direct connections with the thalamus.
The nociceptive receptors and nerves of any given visceral or skeletal structure may project upon the
dorsal horns of several adjacent spinal or brainstem segments the pain from these structures may be fairly
widely distributed
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 Sclerotomes:
o Regions of projection of pain that originates in the bones and adjacent ligamentous structures
o Although dermatomes and sclerotomes overlap, the precise patterns are slightly different
Aberrant Reference:
o Phenomenon explained by an alteration of the physiologic status of the pools of neurons in adjacent
segments of the spinal cord.
For example, cervical arthritis or gallbladder disease, causing low-grade discomfort by constantly
activating their particular segmental neurons, may induce a shift of cardiac pain from its usual locale
to either cephalad or caudad
o Once it becomes chronic, any pain may spread quite widely in a vertical direction on one side of the
body.
D. Chronic Pain
One of the most perplexing issues in the study of pain is the manner in which chronic pain syndromes arise
Theories:
o 1st: In an injured nerve, the unmyelinated sprouts of A fibers and C-fibers become capable of
spontaneous ectopic excitation and after discharge and susceptible to ephaptic activation
(Nerve-to-nerve cross activation)
The injured nerve, even without stimulation, can produce its own excitation to elicit pain stimulus.
o 2nd: These injured nerves are also sensitive to locally applied or intravenously administered
catecholamines because of an overabundance of adrenergic receptors on the regenerating fibers
(May be a basis for causalgia)
In Peripheral nerve injury wherein the body tries to heal itself, will produce nerve endings in the
process but unfortunately when healing is aberrant, will lead to abundance of receptors that are
more sensitive to pain or painful stimulus.
Excites spontaneously with overabundance of receptors, causes continuous or vicious cycle of pain
Central sensory structures
o (e.g. Sensory neurons in the dorsal horns of the spinal cord or thalamus)
o If chronically bombarded with pain impulses, may become autonomously overactive (Being
maintained in this state perhaps by excitatory amino acids) and may remain so even after the
peripheral pathways have been interrupted.
o Example: Phantom limb in an amputated diabetic foot
Peripheral nerve lesions have been shown to induce enduring derangements of central (Spinal cord)
processing
o Example: Avulsion of nerves or nerve roots may cause chronic pain even in analgesic zones
(Anesthesia dolorosa or de-afferentation pain)
The nerve is injured thus the sensation is less, but there is still a complaint of pain.
o Painful states such as causalgia, spinal cord pain, and phantom pain are not abolished simply by
cutting spinal nerves or spinal tracts. (Abnormal discharge subsides in the spinal cord which had been
cut), but is still recorded in thalamus
None of these phenomena can adequately explain the entire story of chronic pain.
Structural changes in the cord are suspected to be able to produce persistent stimulation of pain pathways
Singular attributes of pain
o It does not appear to be subject to negative adaptation
Pain may persist as long as the stimulus is operative (It does not adapt)
o Prolonged stimulation of pain receptors sensitizes them, so that they become responsive to even low
grades of stimulation, even to touch
Allodynia - even if the stimulus is then normal, it is felt as painful due to previous sensitization
In pain continuous stimulation causes overstimulation, lalong sasakit
E. Emotional Reaction to Pain
Another remarkable characteristic of pain is the strong feeling or affect with which it is endowed, nearly
always unpleasant
Since pain embodies this element, psychologic conditions assume great importance in all persistent painful
states
VIII. APPROACH TO THE PATIENT WITH PAIN AS
THE PREDOMINANT SYMPTOM
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 Whenever pain appears to be abnormal or when it constitutes the chief complaint or one of the principal
symptoms, the physician must attempt to reach a tentative decision as to its mechanism and cause seek
out the main characteristics of the pain in terms of the following:
1) Location
2) Mode of onset
3) Associated features
4) Quality and time-intensity attributes
5) Duration
6) Severity
7) Provoking and relieving factors
Some physicians find it helpful, particularly in gauging the effects of analgesic agents, to use a pain scale
have the patient rate the intensity of his pain on a scale of zero (no pain) to ten (worst pain) or to mark it
on a line.

Figure 23. Pain Scale

Once the pains due to the more common and readily recognized diseases of each organ system are
eliminated, there remain a significant number of chronic pains that fall into one of four categories:
1. Pain from an obscure medical disease, the nature of which has not yet been disclosed by diagnostic
procedures (Usually found in connective tissue diseases or neurologic diseases such as multiple
sclerosis)
2. Pain associated with disease of the central or peripheral nervous system (Example: neurogenic or
neuropathic pain)
3. Pain associated with psychiatric disease
4. Pain of unknown cause.
A. Pain due to Undiagnosed Medical Disease
Source of the pain is usually in a bodily organ and is caused by a lesion that irritates and destroys nerve
endings.
The term nociceptive pain is often used, but it is ambiguous.
o It usually means an involvement of structures bearing the termination of pain fibers.
o Carcinomatosis is the most frequent example
B. Neurogenic or Neuropathic Pain
Used interchangeably to designate pain that arises from direct stimulation of nervous tissue
itself, central or peripheral
o Exclusive of pain due to stimulation of sensitized C fibers by lesions of other bodily structures
o In nerve endings, there is neuropathic pain
Comprises a variety of disorders involving:
o Single and multiple nerves, notably trigeminal neuralgia and those due to herpes zoster, diabetes, and
trauma (Includes causalgia)
o Polyneuropathies of diverse type;
o Root irritation (Prolapsed disc)
o Spinal arachnoiditis
o Spinal cord injuries
o The thalamic pain syndrome of Dejerine-Roussy;
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o Rarely parietal lobe infarction

As a rule, lesions of the cerebral cortex and white matter are associated not with pain but with hypoalgesia
Difference between Neuropathic and Neuralgia:
o Neuropathic with disease of peripheral nerve
o Neuralgia no obvious disease of peripheral nerve
o Example:
In trigeminal neuralgia, it was called neuralgia because trigeminal nerve is not abnormal in MRI.
In diabetic neuropathy, it was called neuropathy since distal most nerve endings are damaged by
hyperglycemia, immune conditions etc.
C. Peripheral Nerve Pain
Painful states are in most cases related to disease of the peripheral nerves
o It is pain from this source that the term neuropathic is more strictly applicable.
o Ex. Diabetic polyneuropathy
When the disease of the nerve are undetectable by standard tests.
o the term neuralgia is preferred
o Ex. Trigeminal neuralgia
Postulated mechanisms of peripheral nerve pain:
o Denervation hypersensitivity:
When a group of neurons is deprived of its natural innervation, they become hyperactive
o Reduced density of certain types of fibers in nerves supplying a causalgic zone as the basis of the
burning pain
Comparison is not consistently different
o The occurrence of ectopic impulse generation all along the surface of injured axons and the possibility
of ephaptic (passage of a neural impulse from one nerve fiber, axon or dendrite to another through the
membrane) activation of unsheathed axons seems applicable particularly to some causalgic states
A damaged nerve is capable of spontaneous excitation leading to more pain
o The sprouting of adrenergic sympathetic axons in response to nerve injury is an ostensible explanation
for the abolition of causalgic pain by sympathetic blockade.
o Regenerating axonal sprouts, as in a neuroma, are also hypersensitive to mechanical stimuli.
On a molecular level, it has been shown that sodium channels accumulate at the site of a neuroma
and all along the axon after nerve injury, and that this gives rise to ectopic and spontaneous activity
of the sensory nerve cell and its axon.
C. Causalgia and Reflex Sympathetic Dystrophy
(Complex Regional Pain Syndrome)
The term causalgia is best reserved for the syndrome described
o Persistent burning pain and abnormalities of sympathetic innervation consequent upon trauma to a
major nerve in an extremity.
Complex regional pain syndrome
o Wide range of conditions that are characterized by persistent burning pain but have only an inconstant
association with sudomotor, vasomotor, and trophic changes and an unpredictable response to
sympathetic blockade.
o may follow non-traumatic lesions of the peripheral nerves or even lesions of the CNS (Mimocausalgia)
D. Central Neurogenic Pain
In central lesions, de-afferentation of secondary neurons in the posterior horns or of sensory ganglion cells
that terminate on them may cause the de-afferented cells to become continuously active and, if stimulated
by a microelectrode, to reproduce pain.
o In patients whose spinal cords have been transected, there may be intolerable pains felt below the level
of the lesion.
In the rare cases of intractable pain with lateral medullary or pontine lesions, loss of the descending
inhibitory systems seems a likely explanation.
E. Pain in association with Psychiatric Diseases
It is not unusual for patients with endogenous depression to have pain as the predominant symptom.
Most patients with chronic pain of all types are depressed.

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 Its perplexing because it does not respond to usual pain medications. It is safe to assume that all patients
with chronic pain have an associated depression and those who have depression have some sort of chronic
pain (as a symptom of their depression)
F. Chronic Pain of Indeterminate cause
This is the most difficult, most perplexing group of all because you keep asking yourself, ano ba ito, saan
ba nanggagaling ito
pain in the thorax, abdomen, flank, back, face, or other part that cannot be traced to any visceral
abnormality.
Supposedly all neurologic sources have been excluded by repeated examinations and imaging procedures.
Yet the patient complains continuously of pain, is disabled, and spends a great deal of effort and money
seeking medical aid. Look for a psychologic aspect to that, maybe its psychosomatic pain.
G. Rare and Unusual Disturbances of Pain
Perception
Pain hemiagnosia
Congenital insensitivity to pain
Universal analgesia - congenital
Riley-Day syndrome (Congenital dysautonomia)
Asymbolia for pain(just sensation)
IX. TREATMENT OF INTRACTABLE PAIN
Once the nature of the patients pain and underlying disease has been determined, therapy must include
some type of pain control.
Attention is directed to the underlying disease, with the idea of eliminating the source of the pain by
appropriate medical, surgical, or radiotherapeutic measures.
The difference b/w nociceptive and neuropathic pain, for nociceptive pain, you usually start
with simple analgesics, non-opiate analgesics like, Aspirin, Paracetamol, other NSAIDs. Then
later on, if they are not responding to these, then you can try the narcotic analgesics.
When pain cannot be relieved:
o Attempt to use the milder measures for pain relief first
Example: Non-narcotic analgesics and antidepressants or anticonvulsants
o Narcotics
o Local nerve blocks
o Surgical approaches for pain relief.
The rule of thumb is, you start with milder analgesics and if the pain is controlled, you maintain the patient
on those. But for example on cancer pain, you know that paracetamol wont work so much,so you either
combine Tramadol with Paracetamol or you give something that is more potent analgesic singly. If the
patient still complains of pain, in the Ph we have, oxycodone, morphine, meperidine and fentanyl.
Recap: what do you give a cancer patient who is having multiple episodes of vomiting and is complaining
of pain? Fentanyl. Because its a transdermal patch.
*Please refer to appendix for Table 8-3: Common drugs for the management of chronic pain
X. SUPPLEMENTAL MEDICATIONS FOR THE
TREATMENT OF PAIN
For neuropathic pain, antiepileptic agents like CBZ, Valproate, Gabapentin, Pregabalin or the
antidepressants that work on serotonin and noradrenergic receptors like SSRIs (Sertraline),
SNRI (Duloxetine) and TCAs (good for both pain and mood disorders for chronic pain)
Tricyclic antidepressants, especially the methylated forms (Imipramine, amitriptyline, and doxepin)
o Works on the serotonin and noradrenergic system
o Block serotonin reuptake
o Enhances the action of serotonin at synapses
o Facilitate the action of the intrinsic opiate analgesic system. (Remember your descending pain
modulation system)
Anticonvulsants have a beneficial effect on many central and peripheral neuropathic pain syndromes
o Generally less effective for causalgic pain due to partial injury of a peripheral nerve
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o Blocking of excess sodium channels (MOA of CBZ, Phenytoin, Valproate) reduces evoked and
spontaneous activity in nerve fibers
o In Trigeminal Neuralgia, DOC is CARBAMAZEPINE (CBZ); you dont proceed at once to
morphine. There is a systematic way of managing pain.
Most often, a combination of medications is used for the treatment of intractable chronic pain
o Ex. Gabapentin + Morphine; Pregabalin + Tramadol; Pregabalin + CBZ
Try to augment the effects of different drug groups and do not choose two medications from the
same category. Example, using an anti-convulsant with an opioid analgesic gives better results
XI. TREATMENT OF NEUROPATHIC PAIN
Antiepileptic drugs
Topical
o Capsaicin cream
o EMLA
Spinal injections- for chronic lumbosacral radiculopathy
o Epidural blocks
o Root blocks
o Facet blocks
Injections- for severe myofascial (ie. Nodules) pains, or for those severely contracted, some doctors inject
steroids directly to the belly of the muscle to relax it
o Steroids
o Steroids + analgesics
Intravenous infusions
o Lidocaine
o Mexiletine
Direct injection of the sympathetic ganglia in affected regions of the body-reserved for extreme forms of
pain
o Regional intravenous infusion of sympathetic-blocking drug (Bretylium, guanethidine, reserpine) into a
limb that is isolated from the systemic circulation by use of tourniquet
Example: A Bier block
XII. TREATMENT OF REFLEX SYMPATHETIC
DYSTROPHY
Use of bisphosphonates
Electrical stimulation of the posterior columns of the spinal cord
Epidural infusion of drugs such as ketamine
XIII. ABLATIVE SURGERY IN THE CONTROL OF PAIN
(According to Dra, these are not usually done)
The least destructive procedure consists of surgical exploration for a neuroma if a prior injury or
operation may have partially sectioned a peripheral nerve
Implantation of a spinal electrical stimulator, usually adjacent to the posterior columns
Spinothalamic tractotomy, in which the anterior half of the spinal cord on one side is sectioned at an
upper thoracic level, effectively relieves pain in the opposite leg and lower trunk
Bilateral tractotomy is also feasible, but with greater risk of loss of sphincteric control and, at higher
levels, of respiratory paralysis.
Pain in the arm, shoulder, and neck is more difficult to relieve surgically
o High cervical transcutaneous cordotomy
o Commissural myelotomy by longitudinal incision of the anterior or posterior commissure of the spinal
cord over many segments
o Lateral medullary tractotomy abandoned by neurosurgeons
o Lateral mesencephalic tractotomy abandoned by neurosurgeons
Stereotactic surgery on the thalamus for one-sided chronic pain
o Unpredictable
Cortical ablations
o Unpredictable
XIV. NON-MEDICAL METHODS FOR THE
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TREATMENT OF PAIN
Biofeedback and Meditation are examples of psychotherapies
Imagery
Acupuncture
Some forms of spinal manipulation
Transcutaneous electrical stimulation

Dra. Chua said Study Chapter 8; its all there. But for the interest of time, just study this trans

XV. APPENDIX

Figure 3. Classification and function of sensory peripheral nerve fiber types and symptoms associated with
intrinsic dysfunction of each type. Focus more on A-delta and C fibers.

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Figure 18. Thalamic nuclei and its corresponding cortical map.

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The WHO has stepwise approach to pain management. We start off with Simple analgesics like
Paracetamol, Ibuprofen, if not totally controlled, you can step up, give NSAIDS, and tramadol,
and so that he highest level will be Opiates
Always start with Non opioid analgesics, but before starting we have to figure out if it is
NOCICEPTIVE or NEUROPATHIC. Because the medications that act on neuropathic pain are
different from those that act in nociceptive pain.
If this is NOCICEPTIVE pain, you can start with Non opioid and opioid analgesics. If pain control is
inadequate you can shift to Narcotic analgesics.
Antiepileptic drugs are usually reserved for neuropathic pain.

Editors note: The trans last year contained computations for the drug dosages. We have chosen
not to include them as they were not discussed by the current lecturer.

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