PAIN: BASIC MECHANISMS
INTRODUCTION
und affective and cognitive features:
vays in the
Pain is a complex perception that has profot
Pain is not a stimulus. There are no pain fibers and no pain pathw:
brain. Whether or not a particular stimulus will be perceived as painful depends
on the nature of the stimulus, the situation in which it is experienced, memories,
emotions, and so on.
DEFINITION OF PAIN
ence associated with actual or
“An unpleasant sensory and emotional experi
potential tissue damage” (Internationai Association tor Study of Pain - TASP).
TYPES OF PERSISTENT/CHRONIC PAIN
NOCICEPTIVE/INFLAMMATORY PAIN
Examples include muscle and joint pain (such as-back pain), components of
cancer pain, and tension headache. This type of pain is produced by tissue injury
and is associated with inflammation; it involves activation of A delta and C fibers.
It is responsive to NSAIDS and opiates (morphine).
NEUROPATHIC PAIN
include postherpetic neuralgia, complex regional pain syndrome
limb pain. This type of pain arises from injury to the
quatity. Generally it is
peripheral or central nervous system; it often is burning in
less responsive to opioids, but it may respond to local anesthetics,
anticonvulsants, or tricyclic antidepressants.
PRIMARY AFFERENT NOCICEPTORS
Examples
(CRPS), and phantom
MECHANISMS OF SENSITIZATION
Although there are no “pain” fibers in the perip!
system, there are anatomically and physiologically specialized peripheral afferent
fibers that respond to noxious stimuli. These thinly myelinated A delta and
unmyelinated C afferents terminate as free, unencapsulated peripheral nerve
endings.
Physiological specificity at the level of the primary affere
following: (1) Nerve compression first blocks large
mechanosensation, sensations mediated by small-diam'
perception of noxious stimuli are the last to disappear. (2) Loci
block small-diameter fibers earliest and abolish pain first.
stimulation of single primary afferents in the conscious human su
pain only when thresholds for A delta or C fibers are reached.
5)
hery or in the central nervous
nt is indicated from the
fibers and nonpainful
eter fibers and the
‘al anesthetics
(3) Electrical
bject evokespainful” stimuli, they are \
ne . sence of
AB, affe' it tereentions re omenon indiena
yh the tanger APT uaiity of Boos burning. noter fibers are blocked, |
range dior the level of the dorsa, |
thou!
necessary for the nor fi u eived :
fibers, all noxious stimu! in wen ee
that specificity, ¢ ats “son i
ergence of the a
comemiiicatspneromerers
LG ost common problem
AND HYPERAI . Perel o
ALLODYNIA + most patients complal ot Fovernent, fight touch) become
Allodynia- STE are normall not rae re BY SES errburned sin
clude pain
is that stimuli
painful. Examples of allodynia Im
ent of an arthritic joint. ;
or move core po 7
ee 1
Hyperalgesi Hyperalgesia 'S happens
(e.g., siapping sunburned skin oF what | ap oh
presented to a subject in whose arm
Primary Sensitization. When there is tissue Oe the non-noxioUs range,
the Ac and C nociceptive afferent is lowered H ° ie brane lipids, via the
Mechanisms involve synthesis of arachidonic acid rol He ars aeeealuponiby the
steroid-sensitive enzyme phospholipase Se en s Rei eciy ion the
rost 7
oa Cs Ce : their threshold to natural
‘can now activate aC
peripheral terminais of Ax and C fibers Ser ie
i. it ical threshold is unchanged) light to J
stimuli. (Their electrical tt Leet cease’ Wey
fiber and produce pain. Aspirin and other NSAIDS are ¢'
inhibit cyclooxygenase.
Celecoxib and rofecoxib are drugs that selectively block the COX-2 enzyme. To
the extent that the COX-1 enzyme (which is. blocked by aspirin, ibuprofen, etc.)
underlies side effects of NSAIDs, the COX-2 inhibitors may have particular utility.
duced by noxious stimulus
when nexious stimuli are
ocked by compression).
the threshold for firing of
SUBSTANCE-P
An il-amino acid peptide neurotransmitter synthesized by primary afferent
nociceptors, substance P is released in the dorsal horn and activates second-
order pain” transmission neurons in the dorsal horn. It is released from the
peer terminals of C fibers and contributes to local, neurogenic inflammato!
rechanisms, including vasodilatation, warmth (calor), redness (rubor), a
"
swelling (tumor).
CAPSAICINSPINAL CORD LAMINAR ORGANIZATION
In 1954 Rexed demonstrated that the inal
n 1954 grey matter of the spinal I
divided into cytoarchitecturally distinct 10 laminae or layers. Physiological studies
have since demonstrated an analogous, functional laminar organization. An
electrode penetrating the grey matter of the dorsal horn records cells in the
following sequence. Following are important.
Lamina I (marginal layer) cells respond primarily, and in some cases exclusively,
to noxious stimuli. _Some also respond io innoxious, i.e., non-injurious
stimulation. Many lamina I cells contribute axons to the spinothalamic tract.
wollte II (substantia gelatinosa) contains small interneurons, many of which
respond to noxious inputs. Lamina II neurons modulate ceils of laminae I and V.
estas I an II receive direct primiary afferent input only from small-diameter
ella III and IV cells respond to innocuous stimuli, hair brush, and tactile skin
stimulation, and do not increase their response when the receptive field is
pinched, i.e., with noxious stimulation.
Lamina V cells respond to noxious and non-noxious stimuli and are wide-
dynamic-range (WDR) cells. They also respond to noxious viscera! stimuli and
receive excitatory input from large- and small-diameter efferent fibers.
cord could be
Lamina VI cells respond to joint movement as well as to cutaneous stimulation.
PHYSIOLOGY OF THE WiDE-DYNAMIC-RANGE CELL
In addition to convergence of different modalities of input, WOR neurons in
lamina V receive inputs from a relatively large area in a phenomenon known as
spatial convergence. In fact, single cells in lamina V of the dorsal horn of the
ve a complex receptive field consisting of at least two distinct
spinal cord ha
d noxious stimull”
regions. In the center of the receptive field both innocuous an
are excitatory. In the surrounding regions, non-noxious stimuli (carried by large
fibers) are inhibitory. This factor presumably accounts for the pain-relieving
effects of shaking one’s hand or receiving vibratory stimuli or transcutaneous
electrical nerve stimulation (TENS). By contrast, removal of the inhibitory
components of the receptive field (e.g., after nerve injury) might increase the
a noxious stimulus. Thus, lesions that cause selective
response of a WDR cell to
damage to sources of inhibitory inputs to WDR neurons can produce pain.
SPINAL CORD NEURONS DO NOT TRANSMIT “PAIN”
Clearly, some cells in the dorsal horn of the spinal cord respond to noxious
stimuli, and many of these are at the origin of ascending pathways. Are they
specific “pain” cells? Although some of these neurons respond exclusively to
noxious stimuli, most also respond to non-noxious mechanoreceptive inputs.
They may also be activated by temperature changes thus, several modalities are
carried by the spinothalamic tract axons. There is no “labeled line” for pain.
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