Pathophysiology of the Central
Nervous System
Pain
lecture from Physiology and Pathophysiology II
18. 4. 2023
M. Chalupová
Central Nervous System (CNS)
Degenerative Diseases
• heterogeneous group of disorders of unknown etiology and
pathogenesis
• slow, progressive loss of function in the absence of an
apparent cause (e.g. no infection, neoplasm, vascular disease,
toxicity)
• generally diseases of middle age and later
• most of them are acquired or sporadic, but there are usually
subsets of cases which are inherited (Huntington's disease)
• pathological changes tend to selectively affect certain CNS
subdivisions
Alzheimer's Disease
• most common degenerative brain disease with unknown cause
• incidence rises with age (20% of those over age 80)
• short term memory loss, impairment of executive and mental
functions
• wandering, irritability, incontinence, troubles with language
• gross findings are cerebral atrophy
• micro shows senile plaques, neurofibrillary tangles in neocortex
and limbic regions
• senile plaque has amyloid core, a halo of distorted neurons
• currently no satisfactory treatment
Diseases of the Basal Ganglia
• basal ganglia
– deep brain structures that help start and
control movement
• problems with ability to control
speech, movement and posture
• patient with basal ganglia dysfunction
may have difficulty starting, stopping
or sustaining movement
• depending on which area is affected,
there may also be problems with
memory and other thought processes
HUNTINGTON´S DISEASE
PARKINSON´S DISEASE
Parkinson's Disease (PD)
• sporadic disease with unknown etiology
• expression of cell loss and degeneration involving
the substantia nigra with dopaminergic neurons that
project principally to the striatum (caudate and
putamen)
• their death thus leads to a loss of dopaminergic
innervation to the striatum
• imbalance of dopamine and acetylcholine within the
extrapyramidal system is the biochemical basis for
the signs and symptoms of PD
• triad of rigidity, bradykinesia, tremor
• about one-third develop dementia later
Parkinson's Disease (PD)
Huntington's Disease (Huntington's
Chorea)
• degeneration of the striatum (caudate and putamen)
• autosomal dominant inheritance, mutation on
chromosome 4
• pathogenesis unknown (defective vs. toxic protein)
• movement disorder (chorea, athetosis)
• personality change characterized as depression
progressing to dementia and death
• diagnosis by history, imaging, molecular genetics
Demyelinating Diseases
• myelin sheath, once properly formed and
functioning, is destroyed by a disease process
MULTIPLE SCLEROSIS
Multiple Sclerosis
• myelin sheaths around the axons are damaged, leading
to demyelination
• onset usually occurs in young adults, more common in
females
• etiology unknown (immune or viral factors suspected),
rather multifactorial (genetic and environmental factors)
• multiple zones of demyelination, most numerous in the
white matter of the cerebrum, brain stem, cerebellum
and spinal cord
Multiple Sclerosis
• main clinical feature is the dissemination of signs and symptoms in
time and space, the lesion can occur anywhere in the white matter
of the CNS
• common initial symptoms: diplopia, numbness or weakness of an
extremity, and monocular blindness
• clinical course variable, marked by exacerbations (attacks followed
by remissions), each cycle generally leaves further neurologic
deficit and may involve motor, sensory or cerebellar functioning
• diagnostic methods: MRI, CT scans and evoked potentials
Hypertension Brain Affections
HYPERTENSIVE ENCEPHALOPATHY
• sudden change in blood pressure causes brain vessels spasm,
ischemia and edema
• headache, confusion, somnolence to coma, convulsions
BRAIN STROKE (APOPLEXY)
• ischemic
– thrombosis
• hemorrhagic
– spontaneous intracerebral hemorrhage
– subarachnoid hemorrhage
Brain Stroke
• speaking disorder (aphasia, dysarthria)
• confusion
• muscle weakness, especially on one side of the body
• numbness, especially on one side of the body, decreased sensation
• severe headache
• vision changes (in one or both eyes)
• difficulty with swallowing
• facial droop on one side
• hemiplegia, balance problems
FAST Test Signs of possible stroke
• F means face -- if one side of the face droops
• A means arms -- if the person cannot hold both arms out
• S means speech -- slurring words and poor understanding of simple
sentences
• T means time -- if any of the FAS signs are positive
Inflammatory Diseases of CNS
ENCEPHALITIS
• acute inflammation of the brain usually caused by a
viral infection
• symptoms: headache, neck pain, drowsiness, nausea
and fever
MENINGITIS
• inflammation of the meninges of the brain and spinal
cord
• most often caused by a bacterial or viral infection
• symptoms: fever, vomiting or stiff neck
Pain
• unpleasant sensory and emotional experience
associated with actual or potential tissue damage
• pain stimuli from the skin and the viscera
• distension, temperature, tissue lesions,
inflammation
• pain-producing mediators: leukotrienes,
prostaglandin E2, bradykinin, histamine
Pain
Pain Pathways
Pain Classification
• nociceptive pain arises from the stimulation of specific pain
receptors than can respond to heat, cold, vibration, stretch
and chemical stimuli released from damaged cells
• non nociceptive pain arises from the peripheral and central
nervous system with no specific receptors, pain is being
generated by nerve cell dysfunction
Pain Duration
ACUTE PAIN
• the normal, predicted physiological response to an adverse
chemical, thermal, or mechanical stimulus associated with
surgery, trauma, and acute illness
• generally time-limited and is responsive to analgotherapy
CHRONIC PAIN
• pain state which is persistent and in which the cause of the
pain cannot always be removed or is difficult to treat
• may be associated with a long term incurable or intractable
medical condition or disease
Somatic Pain
• source – skin, muscle, joints, bones and ligaments,
known as musculo-skeletal pain
• specific receptors (nociceptors) for heat, cold,
vibration, stretch (muscles), inflammation (e.g. cuts
and sprains which cause tissue disruption) and
oxygen starvation (ischemic muscle cramps)
• often sharp and well localized and can often be
reproduced by touching or moving the area or tissue
involved
Visceral Pain
• source are internal organs of the thorax (heart and lungs),
abdomen (liver, kidneys, spleen and intestines) and pelvis
(bladder, uterus and ovaries)
• specific receptors (nociceptors) for stretch, inflammation,
and oxygen starvation (ischemia)
• often poorly localized and may feel like a vague deep ache,
sometimes being cramping or colicky in nature
• frequently produces referred pain to the back, with pelvic
pain referring pain to the lower back, abdominal pain
referring pain to the mid-back, and thoracic pain referring
pain to the upper back
Nerve (Neuropathic) Pain
• source is from the nervous system itself (PNS and CNS)
o nerve degeneration – MS, stroke, brain hemorrhage
o nerve pressure – trapped nerve
o nerve inflammation – torn or slipped disc
o nerve infection – viral infections
• no specific receptors for pain, instead of when a nerve becomes injured, it
becomes electrically unstable, firing off signals in a completely
inappropriate, and disordered fashion
• signals are interpreted by the brain as pain, and can be associated with
signs of nerve malfunction such as hypersensitivity (touch, vibration, hot
and cold), tingling, numbness and weakness
• often referred pain to an area where that nerve would normally supply
• spinal nerve root pain often associated with intense itching in the
distribution of a particular dermatome, described as lancinating, shooting
or burning
• partially sensitive to paracetamol, NSAIDs, opioids, more sensitive to antidepressants
and anti-convulsants
Sympathetic Pain
• arises due to possible over-activity of the sympathetic
nervous system
• the sympathetic NS controls blood flow and sweating
• occurs more commonly after fractures and soft tissue injuries
of the arms and legs and injuries may lead to Complex
Regional Pain Syndrome (CRPS)
• no specific pain receptors (non-nociceptive)
• extreme hypersensitivity in the skin around the injury and
peripherally in the limb (allodynia) with abnormalities of
sweating and temperature control
• the limb is painful, patient refuses to use it, causing secondary
problems of muscle wasting, joint contractures, and
osteoporosis
• initiated by trauma to small peripheral nerves close to the
injury
Reffered Pain
• pain perceived at a site adjacent to
or at a distance from the site of an
injury's origin
• ischemia brought on by a
myocardial infarction (heart
attack) where pain is often felt in
the neck, shoulders and back
rather than in the chest
• phantom pain (amputees,
quadriplegics)
Pain Regions
HEADACHE
MYOFASCIAL
RHEUMATIC
PELVIC PAIN
NEUROPATHIC
Headaches (Cephalgia)
PRIMARY
• Tension headaches
• Migraine
• Cluster headaches
SECONDARY
• due to an underlying structural problem in the head or neck
• bleeding in the brain, tumor or inflammatory processes
(meningitis, encephalitis)
CRANIAL NEURALGIAS
Headache (Cephalgia)
TENSION HEADACHES
• the most common type of primary headache (up to 90 % of
adults, more commonly women)
• the pain begins in the back of the head and upper neck and is
described as a band-like tightness or pressure
• the pain usually is mild (not disabling) and bilateral (affecting
both sides of the head)
CLUSTER HEADACHES
• headaches that come in groups (clusters) lasting weeks or
months, separated by pain-free periods of months or years
• pain typically is excruciating and located around or behind
one eye
Migraine
• unilateral pain (affecting one half of the head) and pulsating
in nature, lasting from 4 to 72 hours
• caused by vasodilatation with releasing of chemicals from
nerve fibers that coil around the large arteries of the brain,
this stretches the nerves and causes releasing of the
mediators causing inflammation, pain and other
vasodilatation that magnifies the pain
• nausea, vomiting, photophobia (increased sensitivity to light),
phonophobia (increased sensitivity to sound)
• aura – unusual visual, olfactory or other sensory experiences
that are a sign that the migraine will soon occur
• migraine triggers – stress, sleeping disturbances, odors,
cigarette smoke, hormonal dysbalance