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Fisiologi sistem saraf pusat

transmisi nyeri dari nociceptor perifer ke sumsum tulang belakang dan struktur yang lebih tinggi dari
SSP adalah proces dinamis yang melibatkan beberapa jalur, berbagai reseptor, neurotransmitter dan
utusan sekunder. fungsi dorsal horn sebagai pusat penghubung untuk kegiatan sensorik nociceptive
dan lainnya. tingkat aktivasi menaik sakit sistem proyeksi tergantung pada beberapa faktor
dorsal horn and ascending nociceptive pathway
serat aferen primer dengan sel tubuh mereka di akar dorsal ganglion, terhubung dengan sel saraf
kedua, terletak di tanduk dorsal sumsum tulang belakang. serabut aferen dari perifer nosiseptor
memasuki sumsum tulang belakang di root dorsal dan naik atau turun beberapa segmen di saluran
Lissauer sebelum bersinaps di dorsal horn.
tanduk dorsal terdiri dari enam lamina. lamina I dan II adalah situs pemutusan aferen C-serat dan
dua lamina ini dikenal sebagai gelatinosa substansia. gelatinosa substansia penting bagi integrasi dan
modulasi informasi nociceptive masuk. lamina V adalah situs orde kedua rentang dinamis yang lebar
(WDR) dan niciceptive-spesifik (NS) neuron yang menerima input dari neuron nociseptive dan
entnonnociceptive. neuron NS hanya menanggapi rangsangan berbahaya dalam lingkungan perifer
mereka, sedangkan neuron WDR menanggapi rangsangan berbahaya dan berbahaya dari berbagai
jenis. kedua jenis neuron diyakini impirtant dalam persepsi informasi nociceptive. sering menyatakan
sakit kronis dapat explaind dalam hal masukan ke sel-sel ini dan koneksi supraspinal mereka.

Transmission and modulation
the dorsal horn and its laminae serve as the receiving site for activity initiated on the arrival of action
potentials from the periphery via primary afferent neurons. these primary affernet neurons
terminate in the dorsal hirn and synapse with secondary affernet neurons. these secondary neurons
act as gate cells providing initial modulation of action potential in the dorsal horn. the two main
classes of neurotsansmitters associated with primary afferent nociceptive transmission in the dorsal-
excitatory amino acids are glutamate and neurokinin peptides such as substance P.
thnalamus and cerebral cortex
after leaving the dorsal hirn and ascending via spinothalamic and other pain pathways, nociceptive
action potential reach higher brain centers (reticular formation, midbrain, hypothalamus, cerebral
cortex). Each area of the brain contributes to the pain and its accompanying dangers, alleviate pain
through pain modulation and prevent further tissue damage. In addition, autonomic function, motor
fuction and descending modulating pain pathways respond as a result of activity in this central area.
It is likely that multiple complex brain system are involved when a pain signal reaches the brain. The
cingulate cortex is important in processing nociceptive information.
Cell in laminae I and V are spinotalamic cells, and about 75% of fibers originating from these cells
cross to the contralateral spinotalamic tract. The phylogenetically newer portion of the spinotalamic
tract (neospinotalamic tract) project to the popsterior portion of the thalamus and is considered
connected to the spatial and temporal aspect of pain perception. The phylogenetically older portion
of the spinothalamic (paleospinothalamic) tract projects to the medial thalamus and is responsible
for initiation of unpleasant aspects of pain as well as autonomic nervous system responses to pain.
Other pathways involverd in cephalad transmission of pain impulses include the spinocervical tracts,
spinoreticular tracts, and spinomesencephalic tracts. Pain imoulses travel from the thalamus to
removal of these cortical areas does not destroy the individualsability to perceive pain, suggesting
that the thalamus participates in the conscious perception of pain. It is speculated that the cerebral
cortex is importnat for interpreting the intensity of pain even though perception of pain seems
predominantly to be a function of lower brain centers.
Afferent fibers conducting burning and acing types of pain terminate in the reticular area of the
brainstem. This area transmits activating signals into most area of the brain, aspecially through the
thalamus to the cerebral cortex and hypothalamus. Stimulation of the reticular activating system by
burning and acing pain awakens the individual from sleep and produces generelized activation of the
nervous system. These signals are poorly localized and only alert the individual to continuing tissue
damage. Even weak pain signals via this pathwaynmay summate with time, converting initially
tolerable discomfort into intolerable pain.
both tectile and thermal afferent stimulation has inhibitory influences on pain perception. The basis
of the gate control theory is that A-delta fiber stimulation activates interneurons in the drosal horn
that inhibit the activity of nociceptive transmission neurons. This inhibition is the basis of
transcutaneous electical nerve stimulating, as well as spinal cord stimulating and thalamic
stimulation for pain control.
Gate cells
Gate cells screen action potentials by determining which ones are transmitted to the CNS for
perception. These cells also are invovled in detemining which action potentials result in reflex
responses that serve to move the tissue away from the noxious stimulus and avoid further injury
involvement of inhibitor interneurons that release neurotransmitters such as gamma-aminobutyric
acid (GABA), which also have receptors on these secondary afferent neurons and produce inhibitory
postsynaptic action potentials received from the primary afferent neurons. This gate cell function
determines the nature of axcitation and inhibition action potentials and the resulting effect on
further signal transmission.
Under normal condition, secondary afferent neurons are not spontaneously active but rather are
activated by action potentials generated in the periphery. Similiar to peripheral nociceptors, these
gate cells have a specific physiologic role (regulate incoming action potentials) and a stimulus
threshold that must be reached for epolarization to occur.
Several types of excitatory amino acid receptor are involved in the inititation of excitation that leads
to transmission of pain information. Glutamate is an axcitatory amino acid that is release from
presynaptic endings of hte primary affernet neurons terminating in the dorsal horn. This excitatory
amino acid activates receptors including kainate, AMPA, and NMDA receptors. The action of
glutamate on AMPA receptors causes a rapid depolarization of secondary affernet neurons and
generation of an action potential. In additoin, blinding of glutamate can result in the activation of
cascades of enzymatic processes and second-messenger system that may be modulation than can
occur in the spinal cord. Much like peripheral modulation (bradykinin), glutamate actd neurons
involved in nociceptive processing.
NMDA receptors
NMDA receptors are postsynaptic to the prymary afferent neuron being lacated on the secondary
afferent neuron. Hte NMDA ion channel in blocked bymagnesium ions and under normal
circumstances the secondary afferneeet neurons are not depolarized long enough to permit
magnesium ions to be dislodged and calcium ions to cross. Glutamate is rapidly remove from the
synaptic cleft and thus there is no activity at NMDA receptors in normal nociceptive transmission
processes. However, in the precence of persistent pain arising from abnormal coditions (pheripheral
sensitization, neurophatic pain, chronic pain), the frequency of pain signal transmission increases
resulting in increased amounts of glutamate available in synaptic clefts. As a result, secondary
afferent neurons are depolarized long enough for magnesium ions blocking NMDA receptors serves
to activate secondary messengers and enzymatic processes and generation of various substance
(nitric oxide) that are believed to contributes to enhanced neuronal sensitivity known as central
Protein kinase C activated by activity of excitatory amino acids on NMDA receptors is capable of
uncoupling the opioid receptor mechanism resulting in decrease responsiveness to opioid. As a
result , prolonged opioid administration can lead to spinal sensitization and sustained axcitatory
amino acid release, (accours with neurophathic states) and reduce responsiveness to opioids.

Central sensitization
Central sensitization is believed to be the origin of many chronic pain conditions, especially those
classified as neurophatic. Central sensitozation describes increased excitability of secondary affernet
neurons evoked by neurochemical chnages resulting from activation on NMDA receptors. The
increased excitability of secondary afferent neurons changes the subsequent responses of these
neurons to future input. An increase in the number of action potential generelated by peripheral C-
fiber input in referred to as central wind up or central sensitization. Prolonged input from sensitized
nociceptor resulting from inflammation or spontaneous discharge associated with nerve injury can
cause a chronic state of central sensitization. It is likely that many chronic pain conditions reflect
central sensitization resulting from sustained sensory input from the sustained sensory PNS into the
apinla cord and activation of NMDA receptors. Furthermore, the gatekeeping fuction of secondary
afferent neurons is comprimised, leaving the excitatory effects of pain transmission unopposed. This
results in spontaneous generation of pain signals and exaggerated nervous system responses to
sensory stimuli. Persistent pain can also lead to anatomic changes in both the PNS and CNS.
Following nerve injury, a variety of neuronal plasticity changes occur, such as sprouting of dendrites
on neurons projecting to the dorsal horn or ingrowth of sympathetic fibers likely produce functional
changes characteristic of chronic pain states.
Because the higher levels of the brain cannot discern the origin of the pain signals, the patient is in
a continual tate of pain. It is not known when normal to produce patholigic pain and the point at
which activity accurring at the dorsal horn causes secondary afferent neurons to become chronically
sensitized. What is known is that NMDA receptors are important in facilitating central sensitization
and development of opioid tolerance.
Emotional or physical stress axaserbates central neurophatic pain in up 50% of cases but seldom
accompanies peripheral neurophatic pain. Cold evoked allodynia is more common with central
neurophatic pain. The most common description of spontaneous pain of central neuropahtic pain is
burning or scalding. Oral gabapentin, administerd to healthy volunteers in a regimen similiar to that
used in treating chronic sensitization evokes by intradermal capsaicin. This suggest that the pain
relieving effect in chronic neuropahtic pain is linked to the effect of gabapentin on centrla