Phys Chapter 48
Types of Pain and Their Qualities – Fast Pain and Slow Pain
 Fast pain is sharp, pricking, acute, or electric pain; felt when needle stuck into skin, knife cuts skin, acute burns
o Felt when skin subjected to electric shock
o Not felt in most deeper tissues of body
 Slow pain is slow burning, aching, throbbing, nauseous, and chronic pain; associated with tissue destruction
o Can lead to prolonged, almost unbearable suffering
o Can occur in skin or almost any deep tissue or organ
Pain Receptors and Their Stimulation
 Pain receptors are all free nerve endings; widespread in superficial layers of skin, periosteum, arterial walls, joint
surfaces, falx, and tentorium; most other deep tissues only sparsely supplied with pain endings
o Any widespread tissue damage can summate to cause slow-chronic-aching type of pain in most areas
 In general fast pain elicited by mechanical and thermal pain; slow pain can be elicited by mechanical, thermal, or
chemical
o Chemicals that excite chemical pain are bradykinin, serotonin, histamine, K+, acids, acetylcholine, and
proteolytic enzymes
o Prostaglandins and substance P enhance sensitivity of pain endings but don’t directly excite them
o Chemical substances especially important in stimulating slow, suffering pain after tissue injury
 Pain receptors adapt very little and sometimes not at all; under some conditions, excitation of pain fibers
becomes progressively greater, especially so for slow-aching-nauseous pain as pain stimulus continues
o Hyperalgesia – increase in sensitivity of pain receptors
 Pain resulting from heat closely correlated with rate at which damage to tissues is occurring, not total damage
that has already occurred
 Intensity of pain correlated with rate of tissue damage from causes other than heat (bacterial infection, tissue
ischemia, tissue contusion, etc.)
 Extracts from damaged tissue cause intense pain when injected beneath normal skin; most of chemicals that
excite chemical pain receptors found in extracts
o Bradykinin more painful than others
o Intensity of pain felt correlates with local increase in K+ or increase in proteolytic enzymes that directly
attack nerve endings and excite pain by making nerve membranes more permeable to ions
 When blood flow to tissue blocked, tissue becomes very painful; greater rate of metabolism of tissue, the more
rapidly pain appears
o Accumulation of large amounts of lactic acid in tissues from anaerobic metabolism; bradykinin and
proteolytic enzymes formed because of cell damage
 Muscle spasm – basis of many clinical pain syndromes; results partially from direct effect of muscle spasm in
stimulating mechanosensitive pain receptors; might result from indirect effect to compress blood vessels and
cause ischemia
o Increases rate of metabolism in muscle tissue, making relative ischemia even greater
Dual Pathways for Transmission of Pain Signals into the Central Nervous System
 Fast-sharp pain signals transmitted in peripheral nerves to spinal cord by type Aδ fibers
 Slow-chronic pain transmitted by type C fibers
 Sudden painful stimulus often gives double pain sensation: fast-sharp pain transmitted by Aδ fiber pathway
followed a second or so later by slow pain transmitted by C fiber pathway
o Sharp pain apprises person of damaging influence, making person react immediately
o Slow pain tends to become greater over time
 On entering spinal cord from dorsal spinal roots, pain fibers terminate on relay neurons in dorsal horns
o Fast type Aδ pain fibers transmit mainly mechanical and acute thermal pain; terminate mainly in lamina
I (lamina marginalis) of dorsal horns, and there excite second-order neurons of neospinothalamic tract,
which give rise to long fibers that cross immediately to opposite side of cord through anterior
commissure and turn upward passing to brain in anterolateral columns
 Few fibers of neospinothalamic tract terminate in reticular areas of brain stem, but most pass all
the way to thalamus without interruption, terminating in ventrobasal complex along with dorsal
column-medial lemniscal tract for tactile sensations

Few fibers terminate in posterior nuclear group of thalamus; from there, signals transmitted to
other basal areas of brain as well as somatosensory cortex
 Fast-sharp pain localized much more exactly than slow-chronic pain
 When only pain receptors stimulated without stimulation of tactile receptors, even fast pain
may be poorly localized; when tactile receptors that excite dorsal column-medial lemniscal
system simultaneously stimulated, localization can be near exact
 Glutamate is neurotransmitter substance secreted in spinal cord at type Aδ pain nerve fibers
o Paleospinothalamic pathway transmits pain mainly from peripheral slow-chronic type C pain fibers (does
transmit some signals from type Aδ fibers too)
 Peripheral fibers terminate in spinal cord almost entirely in laminae II and III of dorsal horns
(substantia gelatinosa); most signals pass through one or more additional short fiber neurons
within dorsal horns themselves before entering mainly lamina V (in dorsal horn)
 Neurons from lamina V give rise to long axons that mostly join fibers from fast pain pathway,
passing first through anterior commissure to opposite side of cord, then upward to brain in
anterolateral pathway
 Type C pain fiber terminals entering spinal cord release both glutamate and substance P as
transmitters; glutamate acts instantaneously and short-acting; substance P released more
slowly, building up in concentration over period of seconds or minutes
 Double pain sensation after pinprick might result partly from fact that glutamate
transmitter gives faster pain sensation
 Paleospinothalamic pathway terminates widely in brain stem; few fibers pass all the way to
thalamus (most terminate in reticular nuclei of medulla, pons, and mesencephalon; tectal area
of mesencephalon deep to superior and inferior colliculi; or periaqueductal gray region
surrounding aqueduct of Sylvius
 Lower regions of brain important for feeling suffering pain (brains sectioned above
mesencephalon still evince evidence of chronic pain)
 From brainstem pain areas, multiple short-fiber neurons relay pain signals upward into
intralaminar and ventrolateral nuclei of thalamus and certain portions of hypothalamus and
other basal regions of brain
 Localization imprecise
 Complete removal of somatic sensory areas of cerebral cortex don’t destroy animal’s ability to
perceive pain; electrical stimulation of cortical somatosensory areas causes pain too
 Cortex important in interpreting pain quality
 Electrical stimulation in reticular areas of brainstem and intralaminar nuclei of thalamus (where slow pain
terminates) has strong arousal effect on nervous activity throughout entire body; can’t sleep while in pain
 Cordotomy – cutting cord in thoracic region of spinal cord, relieving pain for few weeks to months; spinal cord
on side opposite pain partially cut in anterolateral quadrant to interrupt anterolateral sensory pathway
o Many pain fibers from upper part of body don’t cross to opposite side of spinal cord until they have
reached brain
o Pain frequently returns several months later as result of sensitization of other pathways normally too
weak to be effectual (e.g., sparse pathways in dorsolateral cord)
 Cauterizing specific pain areas in intralaminar nuclei in thalamus relieves suffering types of pain while leaving
intact appreciation of acute pain
Pain Suppression (Analgesia) System in Brain and Spinal Cord
 Variation in pain tolerance results partly from capability of brain to suppress input of pain signals to nervous
system by activating pain control system (analgesia system)
 Analgesia system consists of: periaqueductal gray and periventricular areas of mesencephalon and upper pons
surround aqueduct of Sylvius and portions of 3rd and 4th ventricles; neurons from there send signals to raphe
magnus nucleus (thin midline nucleus in lower pons and upper medulla) and nucleus reticularis
paragigantocellularis (located laterally in medulla); from nuclei, second-order signals transmitted down
dorsolateral columns in spinal cord to pain inhibitory complex located in dorsal horns of spinal cord; analgesia
signals can block pain before it’s relayed to brain

Stimulation of areas of higher levels of brain (periventricular nuclei in hypothalamus; adjacent to 3rd ventricle)
and to lesser extent medial forebrain bundle (in hypothalamus) excite periaqueductal gray area to suppress pain
 Enkephalin and serotonin involved in transmission in analgesia system; many nerve fibers derived from
periventricular nuclei and periaqueductal gray area secrete enkephalin at their endings; endings of many fibers
in raphe magnus nucleus release enkephalin when stimulated
o Fibers send signals to dorsal horns in spinal cord to secrete serotonin at their endings
o Serotonin causes local cord neurons to secrete enkephalin as well
o Enkephalin causes presynaptic and postsynaptic inhibition of incoming type C and type Aδ pain fibers
where they synapse in dorsal horns
o Analgesia system can block pain signals at initial entry point to spinal cord
o Can block many local cord reflexes that result from pain (withdrawal reflex)
 All opiate-like substances naturally produced in brain are breakdown products of pro-opiomelanocortin,
proenkephalin, or prodynorphin
o Enkephalins found in brainstem and spinal cord
o β-endorphin present in both hypothalamus and pituitary gland
o Dynorphin found mainly in same areas as enkephalins, but in much lower quantities
 Stimulation of large-type Aβ sensory fibers from peripheral tactile receptors can depress transmission of pain
signals from same body area; results from local lateral inhibition in spinal cord
o Mechanism and simultaneous psychogenic excitation of central analgesia system probably basis of pain
relief by acupuncture
 Stimulating electrodes can be placed on selected areas of skin or implanted over spinal cord to stimulate dorsal
sensory columns
o Electrodes placed stereotaxically in appropriate intralaminar nuclei of thalamus or periventricular or
periaqueductal area of diencephalon
Referred Pain
 Branches of visceral pain fibers synapse in spinal cord on same second-order neurons that receive pain signals
from skin; when visceral pain fibers stimulated, pain signals from viscera conducted through at least some of
same neurons that conduct pain signals to skin, and person has feeling that there is pain in skin
Visceral Pain
 Often, viscera have sensory receptors only for pain
 Highly localized types of damage to viscera seldom cause severe pain; any stimulus that causes diffuse
stimulation of pain nerve endings throughout viscus causes pain that can be severe
 Essentially all visceral pain that originates in thoracic and abdominal cavities transmitted through type C fibers
 Ischemia causes visceral pain because of formation of acidic metabolic end products or tissue-degenerative
products such as bradykinin, proteolytic enzymes, or others that stimulate pain nerve endings
 Spasm of portion of gut, gallbladder, bile duct, ureter, or other hollow viscus can cause pain by mechanical
stimulation of pain nerve endings or diminished blood flow combined with increased metabolic need
o Pain occurs in form of cramps, with pain increasing to high degree of severity and then subsiding cyclicly
o Intermittent cycles result from periods of contraction of smooth muscle; each time peristaltic wave
travels along overly excitable spastic gut, cramp occurs
 Extreme overfilling of hollow viscus can result in pain because of overstretch of tissues themselves
o Overdistention can collapse blood vessels that encircle viscus or pass into its wall, promoting ischemia
 Parenchyma of liver and alveoli of lungs almost completely insensitive to pain of any type
o Liver capsule extremely sensitive to direct trauma and stretch
o Bile ducts sensitive to pain
o Bronchi and parietal pleura very sensitive to pain
 Parietal peritoneum, pleura, and pericardium very sensitive to pain, but visceral membranes not; infection
irritates parietal membranes (spread from visceral), causing pain
 Pain from different viscera difficult to localize because patient’s brain only generally recognizes it and sensations
from abdomen and thorax transmitted through 2 pathways (true visceral pathway and parietal pathway)
o True visceral pain transmitted via pain sensory fibers within autonomic nerve bundles; sensations
referred to surface areas of body
o
Parietal sensations conducted directly into local spinal nerves from parietal membranes, and sensations
usually localized over painful area
 Visceral pain referred to surface is in dermatomal segment from which visceral organ originated in embryo
 Pain from viscera frequently localized to 2 surface areas of body at same time because of dual transmission of
pain through referred visceral pathway and direct parietal pathway
Some Clinical Abnormalities of Pain and Other Somatic Sensations
 Primary hyperalgesia – excessive sensitivity of pain receptors themselves; pain such as sunburned skin
 Secondary hyperalgesia – facilitation of sensory transmission; frequently results from lesions in spinal cord or
thalamus
 Herpes virus infects DRG, causing severe pain in dermatomal segment subserved by the ganglion
o Herpes zoster (shingles) because of skin eruption that often ensues
o Cause of pain is infection of pain neuronal cells in DRG by virus
o Virus carried by neuronal cytoplasmic flow outward through neuronal peripheral axons to cutaneous
origins, where virus causes rash that vesiculates
 Tic douloureux (trigeminal neuralgia or glossopharyngeal neuralgia) – lancinating pain occurring over one side of
face in sensory distribution area of CN V or CN IX
o Pain feels like sudden electrical shocks; may be for few seconds or continuous
o Set off by exceedingly sensitive trigger areas on surface of face, in mouth, or inside throat; almost
always by mechanoreceptive stimulus rather than pain stimulus (food touching tonsil while swallowing)
o Pain can be blocked by surgically cutting peripheral nerve from hypersensitive area
 Brown-Séquard syndrome – if spinal cord transected entirely, all sensations and motor functions distal to
segment of transection blocked, but if spinal cord transected on only one side, Brown-Séquard syndrome occurs
o All motor functions blocked on same side of transection in all segments below level of transection
o Sensations of pain, heat, and cold lost on opposite side of body
o Sensations transmitted by dorsal and dorsolateral columns (kinesthetic and position sensations,
vibration sensation, discrete localization, 2-point discrimination) lost on side of transection
Headache
 Brain tissues themselves almost totally insensitive to pain; causes prickly types of paresthesias on area of body
represented by portion of sensory cortex stimulated
 Tugging on venous sinuses around brain (damaging tentorium) or stretching dura at base of brain can cause
intense pain recognized as headache
 Almost any traumatizing, crushing, or stretching stimulus to blood vessels of meninges can cause headache
o Middle meningeal artery particularly sensitive
 Stimulation of pain receptors in cerebral vault above tentorium, including upper surface of tentorium itself,
initiates pain impulses in cerebral portion of CN V and causes referred headache to front half of head
 Pain impulses from beneath tentorium enter CNS mainly through CN IX and X and C2, which also supply scalp
above, behind, and slightly below ear (occipital headache)
 Meningitis causes intense damage and thus causes extreme headache pain referred over entire head
 Loss of CSF pressure/volume causes headache, particularly if patient in upright position; removing CSF removes
part of flotation for brain normally provided by CSF; weight of brain stretches and otherwise distorts various
dural surfaces eliciting pain that causes headache
 Migraine headache may result from abnormal vascular phenomena
o Prolonged emotion or tension causes reflex vasospasm of some arteries of head, including arteries that
supply brain, producing ischemia responsible for prodromal symptoms; as result of intense ischemia,
exhaustion of smooth muscle contraction allows blood vessels to become flaccid and incapable of
maintaining normal vascular tone for 24-48 hours
 BP in vessels causes them to dilate and pulsate intensely
 Excessive stretching of walls of arteries (including some extracranial arteries) causes actual pain
 Headache follows excessive alcohol consumption; alcohol toxic to tissues and directly irritates meninges and
causes intracranial pain
o Dehydration plays role in hangover

Emotional tension often causes muscles of head, especially those attached to scalp and neck muscles attached
to occiput, to become spastic; pain referred to overlying areas of head
 Mucous membranes of nose and nasal sinuses sensitive to pain, but not intensely so
o Infection or other irritative processes in widespread areas of nasal structures summate and cause
headache referred behind eyes or (in case of frontal sinus infection) to frontal surfaces of forehead and
scalp); pain from maxillary sinuses can be felt in face
 Difficulty in focusing eyes may cause excessive contraction of eye ciliary muscles in attempt to gain clear vision
o Tonic contraction of ciliary muscles can cause retro-orbital headache
o Excessive attempts to focus eyes can result in reflex spasm in various facial and extraocular muscles
 When eyes exposed to excessive irradiation by light rays (especially UV), causes headache
o Headache sometimes results from actinic irritation of conjunctivae, and pain referred to surface of head
or retro-orbitally
o Focusing intense light on retina can burn retina, causing headache
Thermal Sensations
 Thermal gradations discriminated by at least 3 types of sensory receptors: cold, warm, and pain receptors
o Pain receptors stimulated only by extreme degrees of heat or cold
 Cold and warmth receptors located immediately under skin at discrete separated spots; in most areas of body,
many more cold spots as warm spots
 Warm signals transmitted mainly over type C nerve fibers
 Cold receptor is small type Aδ myelinated nerve ending that branches several times; tips protrude into bottom
surfaces of basal epidermal cells
o Some cold sensations transmitted in type C nerve fibers
 If skin actually freezes, fibers can’t be stimulated
 Cold receptors adapt to great extent, but never 100%; thermal senses respond markedly to changes in temp as
well as responding to steady states of temp
 Cold and warm receptors stimulated by changes in metabolic rate that result from fact that temp alters rate of
intracellular chemical reactions
 Number of cold or warm endings in any one surface area of body slight, so large skin area stimulated can sense
small changes in temp, but small areas of skin stimulated aren’t as sensitive
 On entering spinal cord, signals travel for few segments upward or downward in tract of Lissauer and terminate
mainly in laminae I, II, and III of dorsal horns (same as pain)
o Small amount of processing by cord neurons, then signals enter long, ascending thermal fibers that cross
to opposite anterolateral sensory tract and terminate in reticular areas of brain stem and ventrobasal
complex of thalamus
o Few thermal signals relayed to cerebral somatic sensory cortex from ventrobasal complex
o Removal of entire cortical postcentral gyrus reduces but doesn’t abolish ability to distinguish gradations
of temperature