PATHOPHYSIOLOGY OF PATHOPHYSIOLOGY OF PAINPAIN

Prof. J. HanProf. J. Hanáčáček, ek, MD, PhDMD, PhD

●● Alteration in sensory function Alteration in sensory function dysfunctions of thedysfunctions of the general or specialgeneral or special sensessenses

•• Dysfunctions of the general sensesDysfunctions of the general senses chronic pain,chronic pain,

abnormalabnormal temperature regulation, tactile dysfunctiontemperature regulation, tactile dysfunction

Definitions of painDefinitions of pain

•• PainPain is a complex unpleasant phenomenon is a complex unpleasant phenomenon

composed of composed of sensorysensory experiences that include experiences that include time, space, time, space, intensity, intensity, emotion, cognition, and motivationemotion, cognition, and motivation

•• PainPain is an unpleasant or emotional experience is an unpleasant or emotional experience originating in real or potential damaged tissueoriginating in real or potential damaged tissue

•• PainPain is an unpleasant phenomenon that is an unpleasant phenomenon that is is

uniquely uniquely experiencedexperienced by each individualby each individual; ; it cannot be it cannot be adequately adequately defined, defined, identified, or measured by an observeridentified, or measured by an observer

The experience of painThe experience of pain

Three Three hierarchial levels hierarchial levels interact usually to produce interact usually to produce complex complex picture of picture of pain:pain:

1.1. sensory -sensory - discriminativediscriminative

2. motivational - affective2. motivational - affective

3. cognitive - evaluative3. cognitive - evaluative

1. 1. Sensory - discriminative systemSensory - discriminative system (location,(location, intensity, quality,intensity, quality, and temporal and spatial aspects of painand temporal and spatial aspects of pain))

2. 2. Motivational - affective systemMotivational - affective system determines the individual´s determines the individual´s

approach-avoidance behavioursapproach-avoidance behaviours (depression, anxiety) (depression, anxiety)

3. 3. Cognitive - evaluative systemCognitive - evaluative system (thoughts concerning the cause and (thoughts concerning the cause and significance of pain).significance of pain). It It may blockmay block or or modulate the perception of painmodulate the perception of pain

Pain Pain ccategoriesategories

1.1. Somatogenic painSomatogenic pain is pain with cause (usually known)is pain with cause (usually known) localised localised in body tissue:in body tissue: a/ nociceptive pain – somatic, viscerala/ nociceptive pain – somatic, visceral

b/ neuropatic painb/ neuropatic pain

22. . Psychogenic painPsychogenic pain is pain for which there is no known physical causeis pain for which there is no known physical cause

but processing of sensitive information in CNS is disturbedbut processing of sensitive information in CNS is disturbed

In this type of painIn this type of pain the psychological evaluation yields evidence that

the pain itself is predominantly sustained by psychological factors

Acute and Acute and cchronic hronic ppainain

Acute painAcute pain is a protective mechanism that alerts the individual to is a protective mechanism that alerts the individual to

a condition or experience that is immediately harmful to the bodya condition or experience that is immediately harmful to the body

OnsetOnset - - usually suddenusually sudden

Relief Relief -- after the chemical mediators that stimulate the after the chemical mediators that stimulate the nociceptorsnociceptors,,

are removedare removed

•• This type of pain mobilises the individual to prompt action to This type of pain mobilises the individual to prompt action to

relief itrelief it

•• Stimulation of autonomicStimulation of autonomic nervous system can be observed nervous system can be observed

during thisduring this

type of paintype of pain (mydriasis, tachycardia, tachypnoe, sweating, (mydriasis, tachycardia, tachypnoe, sweating,

vasoconstriction)vasoconstriction)

Responses to acute painResponses to acute pain

- increased heart rate - - increased heart rate - diaphoresisdiaphoresis

- increased respiratory rate - - increased respiratory rate - blood sugar blood sugar

- elevated blood pressure - - elevated blood pressure - gastric acid gastric acid

secretionsecretion

- pallor or flushing- pallor or flushing,, - - gastric motility gastric motility dilated pupilsdilated pupils -- blood flow to the blood flow to the visceraviscera, ,

kidney kidney and skinand skin - - nausea occasionallynausea occasionally occursoccurs

Psychological and behavioural response to acute Psychological and behavioural response to acute painpain

- fear fear - general sense of unpleasantness o- general sense of unpleasantness orr unease unease

- anxiety- anxiety

Chronic painChronic pain is persistentis persistent or intermittent or intermittent usually defined as usually defined as

lasting at least lasting at least 6 months6 months

The cause is often unknownThe cause is often unknown, , often develops insidiously, often develops insidiously,

vvery ery often is associated with a sense of hopelessness and often is associated with a sense of hopelessness and

helplessness.helplessness. Depression often resultsDepression often results

Psychological response to chronic painPsychological response to chronic pain

Intermittent painIntermittent pain produces a physiologic response produces a physiologic response similar to acute painsimilar to acute pain

Persistent painPersistent pain allows for allows for adaptation adaptation (functions of the (functions of the body are normal but the pain is not reliefed)body are normal but the pain is not reliefed)

Chronic pain producesChronic pain produces significant behavioural and significant behavioural and

psychological changespsychological changes

The main changes are:The main changes are:

- - depression depression

- an attempt to keep pain - related behaviour- an attempt to keep pain - related behaviour to a to a

minimumminimum

- sleeping disorders- sleeping disorders

- - preoccupation with the pain preoccupation with the pain

- tendency to deny pain- tendency to deny pain

Pain Pain tthreshold and hreshold and ppain ain ttoleranceolerance

The pain threshold The pain threshold is the point at which a stimulus is perceivedis the point at which a stimulus is perceivedas painas pain

It does not vary significantly among It does not vary significantly among healthy healthy people or in the same people or in the same person over time person over time

PPerceptual dominanceerceptual dominance-- iintense pain at one locationntense pain at one location of the body of the body

may cause an increase in the pain threshold in another locationmay cause an increase in the pain threshold in another location

• The pain tolerance is expressed as duration of time or the

intensity of pain that an individual will endure before

initiation

overt pain responses.

It is influenced by - persons cultural prescriptions - expectations - role behaviours - physical and mental health

•• Pain tolerancePain tolerance is generally is generally decreaseddecreased::

-- with repeated exposure to pain, with repeated exposure to pain,

- - by fatigue, anger, boredom, apprehension, by fatigue, anger, boredom, apprehension,

- - sleep deprivationsleep deprivation

•• Tolerance to painTolerance to pain may be may be increasedincreased::

-- by alcohol consumption, by alcohol consumption,

- - medication, hypnosis, medication, hypnosis,

- - warmth, distracting activities, warmth, distracting activities,

- - strong beliefs or faith strong beliefs or faith

Pain tolerance Pain tolerance varies greatlyvaries greatly among people and in among people and in the samethe same person over timeperson over time

A decrease in pain tolerance is also evident in A decrease in pain tolerance is also evident in children, children, teenagers and teenagers and elderlyelderly

Age anAge andd pperception of erception of ppainain

Children and the elderlyChildren and the elderly may experience or express pain may experience or express pain

differently than adults differently than adults

InfantsInfants in the first 1 to 2 days of life are in the first 1 to 2 days of life are less sensitiveless sensitive to to

pain pain

(or they simply lack the ability to verbalise the pain (or they simply lack the ability to verbalise the pain

experience).experience).

A full behavioural response to pain is apparent at 3 to 12 A full behavioural response to pain is apparent at 3 to 12

month month

of life of life

Older childrenOlder children,, between the ages of 15 and 18 years, between the ages of 15 and 18 years, tend to have a lower pain threshold than do adultstend to have a lower pain threshold than do adults

Pain threshold tends to increase with ageingPain threshold tends to increase with ageing

This change is probably caused by peripheral neuropathies This change is probably caused by peripheral neuropathies

and changes in the thickness of the skinand changes in the thickness of the skin

Neuroanatomy of Neuroanatomy of ppainain

The portions of the nervous system responsible for the The portions of the nervous system responsible for the

sensation and perception of pain may be divided into three sensation and perception of pain may be divided into three

areas:areas:

1.1. afferent pathwaysafferent pathways

2.2. CNSCNS

3.3. efferent pathwaysefferent pathways

The afferent portionThe afferent portion is composed of:is composed of:

a) nociceptors (a) nociceptors (nerve endings of nociceptive nerve cellsnerve endings of nociceptive nerve cells))

b) afferent nervb) afferent nerve fibrese fibres

c) spinal cord networkc) spinal cord network

Afferent pathways terminate in theAfferent pathways terminate in the dorsal horndorsal horn of theof the spinalspinal cord (1cord (1stst afferent neuron) afferent neuron)

● ● 2nd2nd afferentafferent neuron neuron creates creates spinal part of afferent spinal part of afferent

systemsystem

The portion of CNSThe portion of CNS involved in the interpretation ofinvolved in the interpretation of thethe pain pain signals are thesignals are the limbic system, reticular formation,limbic system, reticular formation, thalamus, thalamus, hypothalamus and cortexhypothalamus and cortex

●● The efferentThe efferent pathwayspathways, , composed of the fiberscomposed of the fibers

connectingconnecting thethe reticular formation, midbrain,reticular formation, midbrain, andand substantia gelatinosasubstantia gelatinosa. . areare

involved in different behavioral and psychological involved in different behavioral and psychological

responsresponses toes to

pain, and thay are responsible pain, and thay are responsible forfor modulatingmodulating pain pain

sensationsensation

The brain first perceives the sensation of painThe brain first perceives the sensation of pain

•• The thalamus, The thalamus, sensitive sensitive cortex :cortex :

perceivingperceiving

describing describing of painof pain

localilocalizzinging

•• Parts of thalamus, brainstem and reticular formation:Parts of thalamus, brainstem and reticular formation: - - identify dull longer-lasting, and diffuse painidentify dull longer-lasting, and diffuse pain

•• The reticular formation and limbic system:The reticular formation and limbic system:

- - control the emotional and affective response to control the emotional and affective response to

painpain

Because the cortex, thalamus and brainstem arBecause the cortex, thalamus and brainstem are e

interconnectedinterconnected

with the hypothalamus and autonomic nervous system, with the hypothalamus and autonomic nervous system,

perceptionperception

ofof pain is associated with anpain is associated with an autonomic response autonomic response

The The rrole of ole of aafferent and fferent and eefferent fferent ppathwaysathways in inprocessing of pain informationprocessing of pain information

Nociceptive painNociceptive pain

Nociceptors:Nociceptors: EndEndingings of small unmyelinated and lightly s of small unmyelinated and lightly

myelinated myelinated

afferent neuronsafferent neurons

Stimulators:Stimulators: CChemical, mechanical and thermal hemical, mechanical and thermal noxaenoxaeMild stimulationMild stimulation positive, pleasurable positive, pleasurable

sensationsensation (e.g. tickling)(e.g. tickling)

Strong stimulationStrong stimulation pain pain

LocationLocation: : IIn muscles, tendons, epidermisn muscles, tendons, epidermis,, subcutanous subcutanous

tissue,tissue, joints, visceral organsjoints, visceral organs

- - they are not evenly distributed in the bodythey are not evenly distributed in the body (in skin more then in internal structures(in skin more then in internal structures))

Nociceptive pain:- mechanisms involved in development

Transduction is the process by which afferent nerve endingsparticipate in translating noxious stimuli (e.g., a pinprick) into nociceptive impulses

Afferent pathwaysAfferent pathways

•• From From nociceptorsnociceptors transmittedtransmitted by by small A-delta fibers and small A-delta fibers and

CC-- fibers fibers to the spinal cordto the spinal cord form synapses with neurons form synapses with neurons

in the dorsal hornin the dorsal horn (DH) (DH)

•• From From DH DH transmitted to higher parts of the spinal cordtransmitted to higher parts of the spinal cord

and to the rest of the and to the rest of the CNS CNS by spinothalamic tractsby spinothalamic tracts

**TheThe small unmyelinated Csmall unmyelinated C-- neurons neurons are responsible for the are responsible for the

transmission oftransmission of diffuse burning or aching sensationsdiffuse burning or aching sensations

**Transmission through the Transmission through the larger, myelinated Alarger, myelinated A- delta- delta fibers fibers

occurs much more quickly. Aoccurs much more quickly. A delta - delta - fibers carry fibers carry well-localized, well-localized,

sharp pain sensationssharp pain sensations

EEfferent analgesic systemfferent analgesic system

Its role: - Its role: - inhibition of afferent pain signalsinhibition of afferent pain signals

Mechanisms:Mechanisms:

- - pain apain afferentfferentss on their way up to CNS send branches toon their way up to CNS send branches to

periaqueductal grayperiaqueductal gray ((PAGPAG) -) - gray matter surroundinggray matter surrounding the the

cerebral cerebral

aqueductaqueduct in the midbrainin the midbrain, and , and stimulastimulatestes the neuronsthe neurons therethere

activation activation of efferentof efferent (descendent) anti-nociceptive (descendent) anti-nociceptive

pathwayspathways

- f- from there the impulserom there the impulsess areare transmitted through the transmitted through the

spinalspinal cord tocord to the dorsal hornthe dorsal horn

-- there thay there thay inhibit or block transmission of nociceptive inhibit or block transmission of nociceptive

signals at signals at

the level of dorsal hornthe level of dorsal horn

Descendent antinociceptive systémDescendent antinociceptive systém

Enk – enkefalinergicPAG – paraaqueductal grayEAA – excitatory amino acidsRVM – rostral ventro-medial medulla

Antinociceptive placebo effect(Zubieta J-Ket al.,2005)

The role of the spinal cordThe role of the spinal cord in pain processing in pain processing

•• MostMost ofof afferent pain fibersafferent pain fibers terminate in the terminate in the DH DH of theof the

spinal segment that they enter. Some, howeverspinal segment that they enter. Some, however, , extend extend

toward the head or the foot for several segments before toward the head or the foot for several segments before

terminatingterminating

•• The The AA-- fibersfibers, , some large A-delta fibers and small Csome large A-delta fibers and small C-- fibers fibers

terminate in the laminae of dorsal hornterminate in the laminae of dorsal horn and and in the substantiain the substantia

gelatinosagelatinosa (SG) (SG) •• The laminaeThe laminae than transmit specific information (about than transmit specific information (about

burnedburned or or crushed skin, about gentlecrushed skin, about gentle pressure)pressure) to 2nd to 2nd

afferent neuronafferent neuron

•• 22ndnd afferent afferent neuronsneurons transmit the impulse from thetransmit the impulse from the SG SG and and laminaelaminae

through thethrough the ventral and lateral hornventral and lateral horn,, crossing in the same crossing in the same or or

adjacent spinaladjacent spinal segmentsegment, , to the other side of the cordto the other side of the cord.. From there From there

thethe impulse is carried through theimpulse is carried through the spinothalamic tractspinothalamic tract to to the brain.the brain.

TheThe two divisions of spinothalamic tract are known:two divisions of spinothalamic tract are known:1.1. the neospinothalamic tractthe neospinothalamic tract - - it carries information to the it carries information to the

mid mid brain,brain, thalamus and thalamus and post central gyrus (where pain post central gyrus (where pain

isis perceived)perceived)

2.2. the paleospinothalamic tractthe paleospinothalamic tract - - it carries information to it carries information to

the the

reticular formation, pons, limbic system, and mid brain reticular formation, pons, limbic system, and mid brain

(more synapses to different structures of brain)(more synapses to different structures of brain)

PAG – periaqueductal grayPB – parabrachial nucleus in ponsVMpo – ventromedial part of the posterior nuclear complexMDvc – ventrocaudal part of the medial dorsal nucleusVPL – ventroposterior lateral nucleusACC – anterior cingulate cortexPCC – posterior cingulate cortexHT – hypothalamusS1, S2 – first and second somatosensory cortical areasPPC – posterior parietal complexSMA – supplementary cortical areasAMYG – amygdalaPF – prefrontal cortex

Theory of Theory of ppain productionain production and modulation and modulation

•• Most rational Most rational explanation explanation of painof pain production and modulation production and modulation

isis based based

onon gate control theorygate control theory (created by Melzack and Wall(created by Melzack and Wall))

•• According to this theory, nociceptive impulses are According to this theory, nociceptive impulses are

transmitted to thetransmitted to the

spinal cord throughspinal cord through large Alarge A- delta- delta and and small Csmall C-- fibers fibers

•• These fibers These fibers create synapses with neurons create synapses with neurons in the in the SGSG

•• The cells in this structureThe cells in this structure function as a gatefunction as a gate,, regulating regulating

transmission transmission

of impulses to CNSof impulses to CNS

Stimulation of largerStimulation of larger nerve nerve fibers fibers (A-alfa, A-beta) (A-alfa, A-beta) causes causes

thethe cells in SG tocells in SG to "close the gate„"close the gate„ for transport of for transport of

painfulpainful

information centrallyinformation centrally..

•• A closed gate A closed gate leads to leads to decreasesdecreases stimulation of T-cellsstimulation of T-cells

(the(the

22ndnd afferent neuron) afferent neuron), , which which decreasedecreases s transmission oftransmission of

impulses, impulses,

andand diminishes pain perceptiondiminishes pain perception

Stimulation of sStimulation of small fibermall fiberss input input inhibits cells in SG andinhibits cells in SG and

"open the gate". "open the gate".

•• An open gate increases the stimulation of T-cellsAn open gate increases the stimulation of T-cells transmission of impulsestransmission of impulses enhances painenhances pain perceptionperception

•• In addition to gate control through large and small fibers In addition to gate control through large and small fibers

stimulation, the central nervous system, throughstimulation, the central nervous system, through efferent efferent

pathways, may close, partially close, or open gatepathways, may close, partially close, or open gate, too, too. .

Cognitive functioning may thus modulate pain perceptionCognitive functioning may thus modulate pain perception

Action of endorphinsAction of endorphins(ED)(ED)

All ED act by attaching to All ED act by attaching to opiate receptorsopiate receptors on the plasma on the plasma

membrane of the membrane of the afferent neuronafferent neuron.. The result than is The result than is

inhibition of releasinginhibition of releasing of theof the neurotransmitter, thusneurotransmitter, thus

blocking the transmission of the painful stimulusblocking the transmission of the painful stimulus

Neuropathic painNeuropathic pain (NP) (NP)

It occurs as aIt occurs as a result of injury to or dysfunction of the result of injury to or dysfunction of the

nervous system itself, peripheral or centralnervous system itself, peripheral or central. The nerve injury . The nerve injury

may be induced by pathology in surrounding tissue. may be induced by pathology in surrounding tissue.

Characteristics of NPCharacteristics of NP – – it may mimic quality of somatic painit may mimic quality of somatic pain

– – it may have characteristic of „disesthetic“it may have characteristic of „disesthetic“

pain (e.g. uncomfortable, unfamiliar sensationpain (e.g. uncomfortable, unfamiliar sensation

such as burning, shock-like, tinglingsuch as burning, shock-like, tingling

– – may be associated with reffered pain, allodynia,may be associated with reffered pain, allodynia,

hyperalgesia, hyperpathiahyperalgesia, hyperpathia

Hyperpathia – Hyperpathia – exaggerated pain responses following a stimulus exaggerated pain responses following a stimulus

often with aftersensations and intense emotionaloften with aftersensations and intense emotional

reactionreaction

What causes neuropathic pain?Neuropathic pain often seems to have no obvious cause; but, some common causes of neuropathic pain include:

- Hereditary disorders - Traumatic nerve damage- Metabolic disorders, - Toxic nerve damage - Nerve ischemia, - Infection of nerve tissue- Nerve compression, - Immune mediated nerve tissue damage

Example of some diseases leading to NP development Alcoholism, Amputation, Back, and Leg, and Hip problems, Chemotherapy, Diabetes mellitus, Facial nerve problems, HIV syndrome, Multiple sclerosis, Shingles (Herpes zoster), Spine surgery What are the symptoms of neuropathic pain?

a) Stimulus indipendent painb) Stimulus evoked pain

Neuropathic pain – subtypes (according a primary location of sustaining mechanism)

a) Predominating peripheral generator:

e.g. compression or entrapment neuropathies, plexopathies,

radiculopathies, polyneuropathies

b) Predominating central generator:

e.g. spinal cord injury,post-stroke pain

Deaferentation painDeaferentation pain - - form of neuropathic pain: a term implyingform of neuropathic pain: a term implying thatthat

sensory deficit in the painful areasensory deficit in the painful area is a prominent is a prominent

featurefeature ((anesthesia dolorosaanesthesia dolorosa))

•• Phantom pain- Phantom pain- pain localizei into non-existing organ (tissue)pain localizei into non-existing organ (tissue)

AllodyniaAllodynia - - phenomenon characterised by painful phenomenon characterised by painful sensationssensations

provoked by nonprovoked by non--noxious stimuli, noxious stimuli, ((e.g. touche.g. touch)), , transmitted by fast- conducting nerve fibrestransmitted by fast- conducting nerve fibres

Mechanism:Mechanism: changes of the response characteristics of changes of the response characteristics of secosecond nd - order- order spinal neuronsspinal neurons,, so that so that normally normally

inactive orinactive or weak synaptic contact mediating weak synaptic contact mediating

nonnon--noxius stimulinoxius stimuli acquire the capability to acquire the capability to

activateactivate a neuron that normally responds a neuron that normally responds

onlyonly

to impulses signaling painto impulses signaling pain

• Hypersensitivity – increased sensitivity of the system involved in the pain processing

• Hyperalgesia – increased the pain sensitivity to noxious

stimuli

Pathomechanisms involved in genesis of neuropathic pain

1) Neurophysiologic and neuroanatomic changes

that may occur in peripherally generated neuropathic pain

a) Abnormal nerve morphology – grow multiple nerve sprouts, – some of these sprouts may form

neuromas

Nerve sprouts and neuromas can

generate spontaneuos activity Areas of spontaneuos activity

(sensitivity) are associated with a change in Na+

receptors concentration

– at sites of demyelination

– are more sensitive to physical stimuli

(manifested as tenderness)

Neural axon injury

Neural axon sprouting and neuroma

Neural axon

b) Development atypical connections between nerve sprouts or demyelinated axons in the region of nerve damage

– permitting „cross–talk“ between somatic or sympathetic efferents and nociceptors

c) Anterograde and retrograde transport of coumpounds stimulation of nerve cell body to production of specific genes

Most Most peripheral neuralgias are the result of trauma or peripheral neuralgias are the result of trauma or

surgerysurgery.. Such a conditions does not necessary occur as Such a conditions does not necessary occur as

a result of damaging a result of damaging aa major nerve trunkmajor nerve trunk but may be but may be

causedcaused by an by an incision involving only small nerve branchesincision involving only small nerve branches

(incisional pain)(incisional pain) MechanismMechanism: : the pain is due to the pain is due to neuroma formationneuroma formation in the in the

scar tissue (?)scar tissue (?)

Common clinical forms of neuropathic painCommon clinical forms of neuropathic pain

Peripheral neuralgias after trauma or surgeryPeripheral neuralgias after trauma or surgery lumbosacral and cervical rhizotomy, lumbosacral and cervical rhizotomy,

●● peripheralperipheral neuralgianeuralgia

Deaferentation pain following spinal cord injuryDeaferentation pain following spinal cord injury

Incidence of severe pain due to spinal cord and cauda equina Incidence of severe pain due to spinal cord and cauda equina lesionslesions rangesranges from 35 to 92 % of patientsfrom 35 to 92 % of patients

This pain is ascribed to This pain is ascribed to 3 3 causescauses::

1. mechanically induced pain (fractur1. mechanically induced pain (fracturee bones, bones,

myofascial pain)myofascial pain)

2. radicular pain (compression of nerve root)2. radicular pain (compression of nerve root)

3. central pain (deaferentation mechanism)3. central pain (deaferentation mechanism)

Psychogenic pain – mechanism

Dysfunction of central mechanisms responsible for processing of sensoric afferent informations

- releasing of mediators decreasing pain threshold

- prolonged muscle contraction due to psychogenic stress

- incresed activity of SNS decreasing pain threhold

- inhibition of activity of descending antinociceptive system

Acute PainAcute Pain

We can distinguish We can distinguish two two types of acute paintypes of acute pain::

1. Somatic1. Somatic

2. Visceral2. Visceral

– – rreferredeferred

Somatic pain is superficialSomatic pain is superficial coming from the skin or close to coming from the skin or close to the surface of the body.the surface of the body.

Visceral painVisceral pain refers to pain inrefers to pain in internal organs, the abdomen, internal organs, the abdomen, oorr chest chest..

Referred painReferred pain is pain that is present in an areais pain that is present in an area removed or removed or

distant from its point of origindistant from its point of origin. The. The area of referred painarea of referred pain

is suppliedis supplied by the nerves from the same spinal segmentby the nerves from the same spinal segment

as the actual site of painas the actual site of pain

Clinical Manifestation of PainClinical Manifestation of Pain

Different types of chronic somatic painDifferent types of chronic somatic pain

I. Nervous system intactI. Nervous system intact

1. nociceptive pain1. nociceptive pain

2. nociceptive - neurogenic pain2. nociceptive - neurogenic pain (nerve trunk pain)(nerve trunk pain)

II. Permanent functional and/or morphological II. Permanent functional and/or morphological abnormalitiesabnormalities

of the nervous systemof the nervous system (preganglionic, spinal - (preganglionic, spinal -

supraspinal)supraspinal)

1. neurogenic pain1. neurogenic pain

2. neuropathic pain2. neuropathic pain

3. deafferentation pain3. deafferentation pain

The most commonThe most common chronic pain chronic pain

1.1. Persistent low back pain Persistent low back pain

– – result of poor muscle tone,result of poor muscle tone, inactivity, inactivity,

muscle strainmuscle strain, , sudden vigorous exercisesudden vigorous exercise

2. Chronic pain associated with cancer2. Chronic pain associated with cancer

3. Neuralgias

4. Myofascial pain syndromes4. Myofascial pain syndromes

5. Hemiagnosia5. Hemiagnosia

6. Phantom limb pain6. Phantom limb pain

NeuralgiasNeuralgias - - results from damages of peripheral nervesresults from damages of peripheral nerves

a)a) CausalgiaCausalgia - - severe burning pain appearingsevere burning pain appearing 1 to 2 weeks after 1 to 2 weeks after

the nerve injury associated with discoloration and the nerve injury associated with discoloration and

changes in the texture of the skin in the affected changes in the texture of the skin in the affected

area.area.

b)b) Reflex sympathetic dystrophiesReflex sympathetic dystrophies - - occur after peripheral occur after peripheral

nerve injury and is characterised by nerve injury and is characterised by continuous continuous

seversevere e burning painburning pain.. Vasomotor changes are Vasomotor changes are

present (vasodilatationpresent (vasodilatation vasoconstriction vasoconstriction cool cool

cyanotic andcyanotic and edematous extremities).edematous extremities).

Myofascial pain syndromesMyofascial pain syndromes - - second most common cause second most common cause

of chronic pain.of chronic pain.

These conditions include: These conditions include: myositis, fibrositis, myalgiamyositis, fibrositis, myalgia,,

musclemuscle strain, injury to the muscle and fasciastrain, injury to the muscle and fascia

The pain is a result ofThe pain is a result of muscle spasm, tenderness muscle spasm, tenderness and stiffnessand stiffness

HemiagnosiaHemiagnosia

– – is a loss of ability to identify the sorce of pain onis a loss of ability to identify the sorce of pain on one one

side side

(the affected side) of the body(the affected side) of the body.. Application of painful Application of painful

stimulistimuli

to the affected side thus produces to the affected side thus produces anxiety, moaning, anxiety, moaning,

agitation agitation

and distressand distress but no attem but no attemppt to withdrawal fromt to withdrawal from or or

push asidepush aside

the offending stimulus. Emotional and autonomic the offending stimulus. Emotional and autonomic

responses responses

to the painto the pain my be intensified.my be intensified.

● ● Hemiagnosia is associated with stroke that produces Hemiagnosia is associated with stroke that produces

paralysis and hypersensitivity to painparalysis and hypersensitivity to painful stimuli ful stimuli in thein the

affected sideaffected side

Phantom limb painPhantom limb pain - is pain that an individual feels in is pain that an individual feels in amputated limbamputated limb

Pathophysiology of muscle painPathophysiology of muscle pain

Muscle painMuscle pain -- a part ofa part of somatic deep painsomatic deep pain,,

(MP)(MP) - - it is commonit is common inin rheumathology and sports rheumathology and sports medicinemedicine

- - is rather diffuse and difficult to locateis rather diffuse and difficult to locate MPMP is not a prominent feature of the serious progressive diseases is not a prominent feature of the serious progressive diseases

affecting muscle, e.g. the muscular dystrophies, denervationaffecting muscle, e.g. the muscular dystrophies, denervation, ,

or metabolic myopathies,or metabolic myopathies, but it is a feature of rhabdomyolysisbut it is a feature of rhabdomyolysis Muscles are relatively insensitive to pain when elicited by needle Muscles are relatively insensitive to pain when elicited by needle prickprick or knife cutor knife cut, , but overlying fascia is but overlying fascia is very very sensitive to painsensitive to pain..

Events, processes which may lead to muscular pain are:Events, processes which may lead to muscular pain are: ● ● metabolic events:metabolic events: •• metabolic depletionmetabolic depletion (( ATP ATP muscular muscular contractcontracture)ure) •• accumulation of unwanted metabolitiesaccumulation of unwanted metabolities (K(K++, , bradykinin)bradykinin)

Pathophysiology of visceral painPathophysiology of visceral pain

Visceral pain:Visceral pain: TTypesypes - angina pectoris, myocardial infarction, acute - angina pectoris, myocardial infarction, acute

pancreatitis, cephalic pain, prostatic pain, pancreatitis, cephalic pain, prostatic pain,

nenephrphrlolytlolythhiatic painiatic pain

Receptors:Receptors: unmyelinated C - fibresunmyelinated C - fibres

For human pathophysiology theFor human pathophysiology the kinds of stimuli apt to kinds of stimuli apt to induceinduce pain in the viscera are importantpain in the viscera are important. .

It is well-known that the stimuli likely to induce cutaneous It is well-known that the stimuli likely to induce cutaneous

pain are not algogenicpain are not algogenic inin the viscera. This explains why in the viscera. This explains why in

the past the viscera werethe past the viscera were considered to be insensitive considered to be insensitive

to painto pain

Adequate stimuliAdequate stimuli of inducing visceral pain:of inducing visceral pain:

1. abnormal 1. abnormal distentiondistention and and contractioncontraction of the hollow of the hollow viscera muscle wallsviscera muscle walls 2. rapid 2. rapid stretchingstretching of the capsule of such solid visceral of the capsule of such solid visceral

organs asorgans as are are the liver, spleen, pancreas... the liver, spleen, pancreas... 3. abrupt 3. abrupt anoxemiaanoxemia of visceral muscles of visceral muscles 4. formation and accumulation of 4. formation and accumulation of pain - producing pain - producing

substancessubstances 5. direct action of 5. direct action of chemical stimulichemical stimuli (oesophagus, stomach (oesophagus, stomach)) 6. 6. traction or compressiontraction or compression of ligaments and vessels of ligaments and vessels

7. 7. inflammatory processesinflammatory processes 8. 8. necrosisnecrosis of some structures (myocardium, pancreas) of some structures (myocardium, pancreas)

Characteristic feature of true visceral painCharacteristic feature of true visceral pain

a) it is dull, deep, not well defined, and differently described by thea) it is dull, deep, not well defined, and differently described by the

patientspatients

b) b) sometimes sometimes it is difficult to locate this type of pain because it it is difficult to locate this type of pain because it

tendstends to to iirrrradiateadiate

c) it is often accompanied by a sense of malaisec) it is often accompanied by a sense of malaise

d) it induces strong autonomic reflex phenomena d) it induces strong autonomic reflex phenomena

-- diffuse sweating, vasomotor responses, changes of arterial diffuse sweating, vasomotor responses, changes of arterial

pressure andpressure and

heart rate, and an intense psychic alarm reaction heart rate, and an intense psychic alarm reaction --"angor "angor

animi" – animi" – e.g. e.g. inin

angina pectoris)angina pectoris)

e) when organ capsules or other structures, e.g. myocardium are e) when organ capsules or other structures, e.g. myocardium are

involved, however, the pain is usually well localized and involved, however, the pain is usually well localized and

described as sharpdescribed as sharp

, stubbing, or thobbing, stubbing, or thobbing

•• There are There are many visceral sensation that are unpleasant but below many visceral sensation that are unpleasant but below the level of painthe level of pain, e.g. feeling of disagreeable fullness or acidity of the , e.g. feeling of disagreeable fullness or acidity of the stomach or undefined and unpleasant thoracic or abdominal stomach or undefined and unpleasant thoracic or abdominal sensation. sensation. These visceral sensation may precedeThese visceral sensation may precede the onset of visceral the onset of visceral painpain

Refered visceral pain (transferred pain)Refered visceral pain (transferred pain)

Refered painRefered pain = when an algogenic process affecting a viscus= when an algogenic process affecting a viscus

recursrecurs

frequently or becomes more intense and prolonged, the frequently or becomes more intense and prolonged, the

locationlocation

becomes more exact and the painfull sensation isbecomes more exact and the painfull sensation is progressively progressively

felt infelt in

more superficial strufturesmore superficial struftures

●● Refered pain may be accompanied by allodynia and Refered pain may be accompanied by allodynia and

cutaneouscutaneous and muscular hyperalgesiaand muscular hyperalgesia

Mechanisms involved in refered pain creation:Mechanisms involved in refered pain creation: a) a) convergence of impulses from viscera and from the skinconvergence of impulses from viscera and from the skin in the CNS:in the CNS:

Sensory impulses from the viscera create an irritable focusSensory impulses from the viscera create an irritable focus in the in the segment at which they enter the spinal cord.segment at which they enter the spinal cord. Afferent impulses from the Afferent impulses from the

skin entering the same segment are therebyskin entering the same segment are thereby facilitated, giving rise to true facilitated, giving rise to true cutaneous pain.cutaneous pain.

b) senzitization of neurons in dorsal hornb) senzitization of neurons in dorsal horn

Painful vPainful visceral afferent impulses isceral afferent impulses activate anterior activate anterior horn horn

motor cells to produce rigidity of the muscle motor cells to produce rigidity of the muscle

(viscero(viscero--motor motor

reflexes)reflexes)

A similar activation of A similar activation of anterolateral autonomic cells anterolateral autonomic cells

induces induces pyloerection,pyloerection, vasoconstriction, and other vasoconstriction, and other sympathetic sympathetic

phenomena phenomena

These mechanisms, which in modern terms can be defined These mechanisms, which in modern terms can be defined as as positive sympathetic and motor feedback loopspositive sympathetic and motor feedback loops, are , are fundamental in reffered painfundamental in reffered pain

It is clear that painful stimulation of visceral It is clear that painful stimulation of visceral structures structures

evokes a evokes a visceromuscular reflexvisceromuscular reflex,, so that so that some some

muscles muscles

contract and become a new source of paincontract and become a new source of pain

It has been observed that the It has been observed that the local anesthetic block of the local anesthetic block of the

sympathetic gangliasympathetic ganglia led to the disappearance, or at least to a led to the disappearance, or at least to a

marked marked decrease, of reffered pain, allodynia, hyperalgesia.decrease, of reffered pain, allodynia, hyperalgesia.

In some conditions, In some conditions, reffered somaticreffered somatic pain is long-lasting, pain is long-lasting,

increases progressively, and is accompanied by increases progressively, and is accompanied by

dystrophydystrophy

of somatic structuresof somatic structures. .

Possible mechanisms: Possible mechanisms: - - onset of self-maintaining onset of self-maintaining vicious circlevicious circle impulses: impulses:

peripheral tissueperipheral tissue afferent fibers afferent fibers

central nervous systemcentral nervous system

peripheral tissueperipheral tissue somatic and sympathetic efferent somatic and sympathetic efferent

fibresfibres

Intricate conditionsIntricate conditions - in some types of pain, - in some types of pain, e.g. e.g. chest painchest pain, , is is difficult difficult

to distinguish the true cause of pain because to distinguish the true cause of pain because such such kind of pain kind of pain

may bemay be

related to cervical osteoarthrrelated to cervical osteoarthrosiosis, esophageal hernia, s, esophageal hernia,

cholecystitischolecystitis, MI,, MI,

other pathologic processesother pathologic processes. It is diffcult to ascertain whether th. It is diffcult to ascertain whether this is

pain ispain is

due to a simpledue to a simple addition of impulses from different sources in the addition of impulses from different sources in the

CNS orCNS or

to to somatovisceralsomatovisceral and and viscerosomatic reflexviscerosomatic reflexeses mechanisms. mechanisms.

It has been demonstrated that the It has been demonstrated that the mnemonic processmnemonic process is facilitated if is facilitated if

the experience to be retained is the experience to be retained is repeated many timesrepeated many times or is accompanied by or is accompanied by

pleasant or unpleasant emotions. pleasant or unpleasant emotions.

PainPain is, at least in part, a is, at least in part, a learned experiencelearned experience - e.g. during the first renal - e.g. during the first renal

colic, true colic, true somatic somatic pain followed visceral pain pain followed visceral pain after a variableafter a variable intervalinterval. .

In subsequent episodes of renal colic pain, In subsequent episodes of renal colic pain, somatic somatic pain pain developed promptlydeveloped promptly

and was not preceded by true visceral painand was not preceded by true visceral pain. .

ThisThis is is probably due to the probably due to the activation of mnemonic tracesactivation of mnemonic traces..

Silent myocardial ischemia (SMI)Silent myocardial ischemia (SMI)

●● Chest pain is only a late and inconstant marker of episodes Chest pain is only a late and inconstant marker of episodes

ofof

transient transient MI MI in vasospastic angina (30 %), in stablein vasospastic angina (30 %), in stable angina angina

(50 %)(50 %)• Mechanisms ofMechanisms of SMI SMI

a) Lack of the pain is, in part, related to thea) Lack of the pain is, in part, related to the duration and severityduration and severity

ofof MI MI. . EpisodesEpisodes shorter than 3 minshorter than 3 min, , and those accompanied by and those accompanied by

aa modest impairment of left ventriclemodest impairment of left ventricle (( in end-diastolic pressure in end-diastolic pressure

inferior to 6 mm Hg) areinferior to 6 mm Hg) are alwaysalways painlesspainless..

Longer and more severeLonger and more severe episodes are acccompaniedepisodes are acccompanied by chest by chest

pain pain in some instances but not in othersin some instances but not in others. .

b) Pacients with predominantly b) Pacients with predominantly SMI SMI appear to haveappear to have a a generalizedgeneralized

defective perception of paindefective perception of pain ((threshold andthreshold and tolerance).tolerance).

MechanismMechanism: : level of circulating level of circulating -endorphin (?)-endorphin (?)

Disturbances in Disturbances in ppain ain pperception and erception and nnociceptionociception

Most of the disturbances areMost of the disturbances are congenitalcongenital

a)a) Congenital analgesiaCongenital analgesia - - nociceptive stimuli are nociceptive stimuli are notnot processed processed

and/or integrated at a level of brainand/or integrated at a level of brain. .

Patient doesPatient does not feel a painnot feel a pain

b) Congenital sensoric neuropathyb) Congenital sensoric neuropathy - - nociceptive stimuli are nociceptive stimuli are not not transmittedtransmitted by by peripheral peripheral nerves ornerves or by spinal afferent by spinal afferent tractstracts..

Acquired disturbancesAcquired disturbances in pain perception and nociceptionin pain perception and nociception

They may occur at They may occur at syringomyelysyringomyely, , disturbances of parietal lobe of disturbances of parietal lobe of

brain, in patients suffering from neuropathy brain, in patients suffering from neuropathy (e.g. chronic diabetes mellitus)(e.g. chronic diabetes mellitus)

Development of neuropathic chronic pain after spinal cord injury

Neural axon Neural axon injury

Measurements of pain intensity