10. NOCICEPTION & PAIN


통각기능: 신체보호
통각의 정의: actual or potential tissue damage
unpleasant sensory, emotional experience

10. 1. The Characterization of Pain

Pain Qualities

Location:
+-Somatic: +-superficial (initial & delayed)
| +-deep, e.g., chronic, acute joint pain
|
+-Visceral: e.g., gall bladder, renal pelvis의 강한 stretch, contraction

Duration:
+-Acute: e.g., burning, where, how long: Signal & warning 기능
+-Chronic: e.g., back pain, tumor, migrane headache
: No Physiological Function
: 실제 손상 =\= 고통의 강도
: 장소 ...... separate syndrome
: psychogenic pain

Itch:
pain과 유관: Itch points=pain points, 같은 pathway
pain과 무관: epidermis의 외층에서만

Components of Pain

Sensory discriminative: 언제(始終), 어디서, 얼마나
Affective (emotional): unpleasant
Autonomic: blood pressure, heart rate, respiration, visceral pain
Motor: escape of protection reflex
Cognitive: evaluation of pain, past experience

여러 System이 관여 (동시, 따로) 발현

각 component측면에서 evaluation
가정적, 사회적, 민족적, 교육적 측면, 통증발생 상황

The Measurement of Pain (Algesimetry)

Noxious stimulation (thermal, electrical, mechanical, chemical)
---->Pain (subjective expression: threshold, intensity, tolearance threshold)

lack of adaptation, sensitization, habituation

Objecctive:
motor & autonomic reaction의 측정
evoked potentials from cerebral cortex

Methods of ratio estimation
McGill Pain Questionnaire
Tourniquet Pain Quotient

10.2 Neurophysiology of Pain

Pain points(nociceptors): 多多多 9:1 > pressure points > 냉,온점
Transduction & Transformation in Nociceptors

Modality & Structure of the nociceptors
대부분 multimodal nociceptors (mechanical, thermal, chemical)
free (non-corpuscular) nerve ending
Nociceptors are the least differentiated of
the sensory receptors in the skin.
prime noxa (bacterial infection, mechanical force, heat, cold)
---> chain reation in cell & tissue
---> release of algogenic substances
(prostaglandins, bradykinin, serotonin, etc.)
---> generator potnetial---> Action Potential
Substance P--->Histamine from mast cells
--->vasodilation
---> spread of edema & hyperalgesia
Prostaglandin E2: a cyclo-oxygenase metabolite of arachidonic acid
: produce hyperalgesia & sensitize nociceptors
# aspirin and other nonsteroidal anti-inflammatory
analgesics: inhibit the cyclo-oxygenase enzyme,
preventing the synthesis of prostaglandin.
Bradykinin: one of the most active pain-producing agents
: activating A-delta & C nociceptors
: increases the synthesis & release of prostaglandins
from nearby cells

Sensitization: threshold 감소, algesic substances
at peripheral & central terminals of primary afferent
Hyperalgesia: primary hyperalgesia: at site of the tissue damage
secondary hyperalgesia: in the surrounding undamaged
Desensitization: threshold 증가, analgesic substances

Peripheral Conduction of Noxious Signals
cell bodies: DRG, TG

1) Group III (A-delta fibers) thin myelinated
CV=2.5-30 m/sec,
initial pain in superfical pain
sharp & pricking pain
sensitive to pressure block
thirmal nociceptors, mechanical nociceptors

2) unmyelinated Group IV (C-fibers)
CV=less than 2.5 m/s
Polymodal nociceptors
(high-intensity mechanical, chemical, heat (45oC), cold)
transduction mechanism for each type of of noxious stimulus
is distinct. (개개 자극종류에 따른 threshold response가 서로 다름)
多多 delayed pain (dull, burning)
more sensitive to local anesthetic
대부분의 visceral afferents

Central Conduction & Processing of Noxious Signals
A-delta & C-fibers: spinal cord로 들어가서 bifurcate
Lissauer tract을 타고 ascend or descend
Afferents to Spinal Dorsal Horn
layer I (marginal zone): A-delta,
high density of projection neurons
layer II (substantia gelatinosa): C-fibers, output layer III
layer III: from layer II (C input)
layer IV: A-alpha & A-beta, from layer V (A-delta)
layer V: A-delta, output to layer IV

types of neurons:
Projection N.: relay incoming sensory information to higher ctrs.
Local excitatory N.: relay sensory input to projection neurons.
Inhibitory N.: regulate the flow of nociceptive information

Two Major Cell Types:
Noceceptive specific N. (NS, HT): layer I
excited soley by nociceptors
Wide Dynamic Range N. (WDR): layer I, V & VI
excited by nociceptors & by low-threshold mechanoreceptors

Neurotransmitters: Glutamate, Substance P, Enkephalin 등등
:small electron-translucent synaptic vesicles: excitatory amino acids
A-delta fiber에 다, evokes fast synaptic potentials
:large dense-core vesicles: neuropeptides
C-fiber에 다, elicit slow excitatory PSP

Five Major Ascending Pathways:










BRAIN FACTS


1. Spinothalamic tract
most prominent ascending nociceptive pathway
from layers I, V-VII,
NS, WDR cells,
crosses the midline
anterolateral funiculus
terminate in the thalamus
lesion--->marked deficit in pain sensation
Electrical stimulation---> pain perception

2. Spinoreticular tract
from layers VII, VIII
crossing/uncrossing
anterolateral quadrant of the spinal cord를 타고 상승
terminate in the reticular formation of the medulla & pons
(some in thalamus)

3. Spinomesencephalic tract
from layers I, V
project to midbrain, mesencephlaic reticular formation
(periaqueductal gray (PAG), RF)

4. Spinocervical tract
from layers III, IV
대부분 tactile
dorsolateral SC---> lateral cervical Nucleus --(cross)-> ML

5. Dorsal Column System
from layers III, IV
---> cuneate & gracile nuceli in the medulla

Thalamic Nuclei
Medial Nuclear Group (Central Lateral Nucleus, Intralaminar compex):
input from SC layers VI-VIII,
indirect input through RF (bilateral, spinoreticular tract)
large complex receptive fields
wide spread projection to cortex & basal ganglia
not exclusively concerned with processing of nociceptive 정보
part of the nonspecific arousal system
Lateral Nuclear Group (Ventrobasal nucleus, Posterior nuclei):
input from NS, WDR cells in SC laminae I & V

In Cortex
2 classes of neurons
small RF: from VB
large, diffuse, often bilateral RF: from IL, CL, Po
Modality: NS, WDR
No distinct topography
damage to large areas of the somatosensory cortex
---> no loss of pain sensation

Pain Modulation at Spinal Cord
variability of pain sensation: ---> modulatory system in CNS to regulate pain
the joy of childbirth can suppress pain
fear of the dentist can intensify pain

<Gate Control Theory> (by Patrik Wall & Ronald Melzack), early 1960
pain perception is sensitive to levels of activity in both
nociceptive & nonnociceptive afferent fibers.
Projection neuron: activated by both the low-threshold myelinated &
unmyelinated fibers
noxious input---> inhibit the inhibitory interneurons
nonnoxious inputs---> activate inhibitory interneuron
---> inhibit the projection N. (noxious input from C-fibers)
(thus reducing the perception of pain)
응용: Dorsal Column Fiber 자극---> reducing pain
TENS: Peripheral nerve 자극
Modification of Gate control theory
presynaptic inhibition
descending inhibition

<Descending pain inhibitory pathways>
Stimulation produced analgesia (SPA)
Ventrobasla thalamus, Internal capsule
PAG (Periaqueductal gray matter)---> rostroventral medulla
NRM (serotonergic Nucleus raphe magnus, input from PAG)
Nucleus paragigantocellularis
descending through dorsolateral funiculus
---> inhibiting neurons in SC layers I,II,V
Opiate analgesia
Morphine 투여 at above system
reversed by naloxone (narcotic antagonist)
Opiate receptor 有
endogenous opioid peptides: three classes
all contain the sequence Tyr-Gly-Gly-Phe
Endorphins,
Enkephalins,
Dynorphin family

10. 3 Pathophysiology of Nociception & Pain
Projected Pain:
e.g., nerve 자극: 그 nerve가 innervate한 지역의 pain으로 느낌
compression of spinal nerve
Neuralgia:
continuous irritation of a nerve or a dorsal root
(chronic nerve damage)---> spontaneous pain

Deafferentation pain:
motor cycle injury
: dorsal root가 pulled away from the spinal cord
(brachial plexus avulsion)
: burning or electric pain in the dermatomes
corresponding to the denervated area.
: because of the hyperactivity of dorsal horn neurons in the
deafferented region of the spinal cord
: 치료: surgical ablation of the superficial dorsal horn
Phantom pain: chronic overactivity of dorsal horn neurons

Causalgia: (reflex sympathetic dystrophy syndrome)
: activity of efferent fibers of the sympathetic nervous system
following peripheral nerve injury
---> activation of damaged nociceptive afferents

Referred Pain:
e.g. visceral organ---> 체외의 body part, same segment of SC
원인:
Convergence of afferents onto the same dorsal horn projection neurons.
Branching of primary nociceptive afferents

Allodynia:
non-noxious stim---> pain
Hyperalgesia: oversensitive to noxious stimulation
Hyperpathia: increased response w/h delayed onset & an afterresponse
Hypoalgesia: noxious stimulation에 대한 sensitivity가 감소
Analgesia: noxious stimulation에 대한 반응 無
Anesthesia: noxious & nonnoxious 모두 반응 안함
Complete congenital insensitivity to pain
Central Pain : thalamic pain, phantom pain, anesthesia dolorosa
thalamic pain: lesions in the thalamus (VB)


10.4 Exogenous Inhibition of Pain

1) Pharmacological Methods
non-narcotic analgesics: without abolishing consciousness
e.g. acetylsalicylic acid
narcotic analgesics
e.g. morphin
psychotropic drugs
e.g., tranquilizers, antidepressants
local anesthesia
nerve blocking, receptor inactivation

2) Physical methods
Heat, cold
massage, 전기자극 (rubbing, scratching)
gymnastics, Neurosurgery, exercises
acupuncture

3) Psychological Methods
Hypnosis
Relaxation & meditation etc.










BRAIN FACTS