PATHOPHYSIOLOGY OF PAIN Prof. J. Hanáček, MD, PhD Technical co-operative: L.Šurinová, Ing. M. Vrabec.

PATHOPHYSIOLOGY OF PATHOPHYSIOLOGY OF PAINPAIN

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

Technical co-operative: L.Šurinová, Ing. M. Vrabec

●● Alteration in sensory function Alteration in sensory function dysfunctions dysfunctions of theof the general or general or specialspecial sensessenses •• Dysfunctions of the general sensesDysfunctions of the general senses chronic chronic pain,pain, abnormal temperature regulation, tactile abnormal temperature regulation, tactile dysfunctiondysfunction

Definitions of painDefinitions of pain•• PainPain is a complex unpleasant phenomenon composed of is a complex unpleasant phenomenon composed of sensorysensory experiences that include experiences that include time, space, intensity, time, space, 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 uniquely is uniquely experiencedexperienced by each individualby each individual; it cannot be adequately ; it cannot be adequately defined, defined, identified, or measured by an observeridentified, or measured by an observer

The experience of painThe experience of pain

Three systems interact usually to produce pain:Three systems interact usually to produce pain: 1.1. sensory -sensory - discriminativediscriminative

2. motivational - affective2. motivational - affective

3. cognitive - evaluative3. cognitive - evaluative

1. 1. Sensory - discriminative systemSensory - discriminative system processes information about processes information about tthehe strength, intensity, strength, intensity, quality quality and temporal and spatial and temporal and spatial aspects of painaspects of pain

2. 2. Motivational - affective systemMotivational - affective system determines the individual´s determines the individual´s approach-avoidance behavioursapproach-avoidance behaviours

3. 3. Cognitive - evaluative systemCognitive - evaluative system overlies the individuals learnedoverlies the individuals learned

behaviour concerning the experience of pain. behaviour concerning the experience of pain. It It may block, may block,

modulate, or enhance the perception of painmodulate, or enhance 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 in the body tissuelocalised in the body tissue a/ nociceptive paina/ nociceptive pain b/ neuropatic painb/ neuropatic pain

22. . Psychogenic painPsychogenic pain is pain for which there is no known is pain for which there is no known physical causephysical cause but processing of sensitive information but processing of sensitive information in CNS is dysturbedin CNS is dysturbed

Acute and Acute and cchronic hronic ppainain

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

individual to a condition or experience that is immediately individual to a condition or experience that is immediately

harmful to the bodyharmful 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 removed are removed

•• This type of pain mobilises the individual to prompt action This type of pain mobilises the individual to prompt action to relief itto relief it

•• Stimulation of autonomicStimulation of autonomic nervous system can be observed nervous system can be observed during this type of painduring this type of pain ((mydriasis, tachycardia, tachypnoe, mydriasis, tachycardia, tachypnoe,

sweating, vasoconstriction)sweating, 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 usually defined

as lasting at least as 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 often is associated with a sense of hopelessness

and 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 pain.similar 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 painIt 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 location may cause ntense pain at one location may cause

an increase in the pain threshold in another locationan 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 the A decrease in pain tolerance is also evident in the

elderly, elderly,

and women appear to be more and women appear to be more tolerant tolerant to pain than to pain than

menmen

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 of life month 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 (pain receptors)a) nociceptors (pain receptors)

b) afferent nervb) afferent nerv fibres 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 spinal part of

afferent afferent systemsystem

The portion of CNSThe portion of CNS involved in the involved in the interpretation ofinterpretation of

thethe pain signals are thepain signals are the limbic system, limbic system,

reticular reticular

formation,formation, thalamus, hypothalamus and cortexthalamus, hypothalamus 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 responsible forresponsible for modulatingmodulating pain sensationpain sensation

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

localisinglocalising

•• 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 aree

interconnected with the hypothalamus and autonomic interconnected with the hypothalamus and autonomic

nervous system, thenervous system, the perception ofperception of pain is associated pain is associated

with anwith an

autonomic response autonomic response

The The rrole of the ole of the aafferent and fferent and eefferent fferent ppathwaysathways in in

processing of pain informationprocessing of pain information

Nociceptive painNociceptive pain

Nociceptors:Nociceptors: EndEndingings of small unmyelinated and lightly s of small unmyelinated and lightly myelinated afferent neuronsmyelinated afferent 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

ThTheseese differences are a result of the differences are a result of the frequency frequency and amplitudeand amplitude of the afferent signal of the afferent signal transmittedtransmitted from the nerve endingsfrom the nerve endings to the CNS to the CNS

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

tissue,tissue, visceral organsvisceral 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

Afferent pathwaysAfferent pathways::

•• From From nociceptorsnociceptors transmitted transmitted 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 - - 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 a- pain afferentfferentss stimula stimulatestes the neuronsthe neurons in in

periaqueductal periaqueductal

graygray ((PAGPAG) -) - gray matter surroundinggray matter surrounding the cerebral the cerebral

aqueductaqueduct in the midbrain results inin the midbrain results in activation activation of of

efferentefferent

(descendent) anti-nociceptive(descendent) anti-nociceptive pathways pathways

- - ffrom there the impulserom there the impulsess areare transmitted through transmitted through thethe spinalspinal cord tocord to the dorsal hornthe dorsal horn

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

nociceptive nociceptive signals at the level of dorsal hornsignals at the level of dorsal horn

Descendent antinociceptive systémDescendent antinociceptive systém

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

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

•• MostMost afferent pain fibersafferent pain fibers terminate in the dorsal hornterminate in the dorsal horn 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 •• 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 substantiasubstantia

gelatinosagelatinosa (SG) (SG) and laminae and laminae through thethrough the ventral and ventral and lateral hornlateral horn,,

crossing in the same or adjacent spinalcrossing in the same or adjacent spinal segmentsegment, , to the to the other sideother side

of the cordof the cord.. From there theFrom there the impulse is carried through theimpulse is carried through the

spinothalamic tractspinothalamic tract to the brain. Theto the brain. The two divisions of two divisions of

spinothalamic tract are known: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 painproduction and modulationproduction and modulation

isis based on based on 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 the spinal cord throughtransmitted to the spinal cord through large Alarge A- delta- delta and and small Csmall C-- fibers fibers

•• These fibers These fibers create synapses create synapses 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".

•• A closed gate decreasesA closed gate decreases stimulation of T-cellsstimulation of T-cells (the 2(the 2ndnd

afferent neuron)afferent neuron), , which which decreasedecreases s transmission of transmission of

impulses, impulses,

andand diminishes pain perceptiondiminishes pain perception

Stimulation of sStimulation of small fiber inputmall fiber 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 gate. pathways, may close, partially close, or open gate.

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

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

Deaferentation painDeaferentation pain - - form of neuropathic pain: a term form of neuropathic pain: a term

implyingimplying thatthat sensory deficit in the painful areasensory deficit in the painful area is is

a prominent featurea prominent feature ((anesthesia dolorosaanesthesia dolorosa))

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

•• Long-lasting pain after short-lasting pain stimulusLong-lasting pain after short-lasting pain stimulus

What causes neuropathic pain?

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

Alcoholism, Amputation, Back, Leg, and Hip problems, Chemotherapy, Diabetes mellitus, Facial nerve problems, HIV infection or AIDS Multiple sclerosis, Shingles (Herpes yoster), Spine surgery

What are the symptoms of neuropathic pain?

Symptoms may include:

Shooting and burning pain, Tingling and numbness

AllodyniaAllodynia - - phenomenon characterised by painful phenomenon characterised by painful

sensations provoked by nonsensations provoked by non--noxious stimuli, noxious stimuli,

((e.g. touche.g. touch)), transmitted by fast- conducting , transmitted by fast- conducting

nerve fibresnerve fibres

Mechanism:Mechanism: changes of the response characteristics of changes of the response characteristics of secosecond nd - order- order spinal neuronsspinal neurons so that normally so that 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 onlya neuron that normally responds only

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

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 damageing a result of damageing 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 (?)

Peripheral neuralgias after trauma or surgeryPeripheral neuralgias after trauma or surgery

Common forms of neuropathic painCommon forms of neuropathic pain

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)

Acute PainAcute PainWe 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 - supraspinal)(preganglionic, spinal - 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,inactivity, result of poor muscle tone,inactivity,

muscle strainmuscle strain, , sudden vigorous exercisesudden vigorous exercise

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

3. Neuralgias3. Neuralgias - - 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).

4. Myofascial pain syndromes4. Myofascial pain syndromes - - second most common cause second most common cause

of chronic pain.of chronic pain.

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

5. Hemiagnosia5. Hemiagnosia

– – 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

6. Phantom limb pain6. Phantom 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,

nenephrphrlolytiatic painlolytiatic 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 distention and contraction of the hollow 1. abnormal distention and contraction of the hollow viscera muscle wallsviscera muscle walls 2. rapid stretching of the capsule of such solid visceral 2. rapid stretching of the capsule of such solid visceral

organs asorgans as are are the liver, spleen, pancreas... the liver, spleen, pancreas... 3. abrupt anoxemia of visceral muscles3. abrupt anoxemia of visceral muscles 4. formation and accumulation of pain - producing 4. formation and accumulation of pain - producing

substancessubstances 5. direct action of chemical stimuli (oesophagus, stomach5. direct action of chemical stimuli (oesophagus, stomach)) 6. traction or compression of ligaments and vessels6. traction or compression of ligaments and vessels

7. inflammatory processes7. inflammatory processes 8. necrosis of some structures (myocardium, pancreas)8. necrosis of some structures (myocardium, pancreas)

Characteristic feature of true visceral Characteristic feature of true visceral painpain

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

b) b) sometimes sometimes it is difficult to locate this type of pain it is difficult to locate this type of pain because it because it tends to tends 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 (much more pronounced than in pain of somatic (much more pronounced than in pain of somatic origin) origin) -- diffuse sweating, vasomotor responses, changes diffuse sweating, vasomotor responses, changes of of

arterial pressure and heart rate, and an intense arterial pressure and heart rate, and an intense

psychic psychic

alarm reaction alarm reaction --"angor animi" - in angina "angor animi" - in angina

pectoris)pectoris)

•• 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 = when an algogenic process affecting a

viscusviscus 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

(visceromotor (visceromotor

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, e.g. - in some types of pain, e.g. chest pain, chest 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, or s, esophageal hernia, or

cholecystitischolecystitis. It is . It is

diffcult to ascertain whether these intricate conditions are due to diffcult to ascertain whether these intricate conditions are due to

a simplea simple

addition of impulses from different sources in the CNS or to addition of impulses from different sources in the CNS or to

somatovisceralsomatovisceral

and and viscerosomatic reflex mechanisms.viscerosomatic reflex 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 parietal pain followed visceral pain colic, true parietal pain followed visceral pain after a variableafter a variable intervalinterval. .

In subsequent episodes of renal colic pain, parietal pain In subsequent episodes of renal colic pain, parietal 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 notnociceptive stimuli are not processed processed

and/or integrated at a level of brain. and/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 not nociceptive stimuli are not transmitted bytransmitted 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)