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Neural and Hormonal Control of

Human Systems

Lecture 2:
Pain (chapter 10)
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How Can We Define PAIN?

 Is it uni or multidimensional…?
Multi: sensory, affective (emotional), autonomic

 Can it be measured?
Yes: visual analogue scale, pain McGill
questionnaire

 Can it be beneficial for the body?

Yes: localization & compensatory mechanisms

 Should we say a nociceptive or a painful

sensation?
Nociceptive: before signal reaches awareness
Pain: once signal is interpreted in the brain
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Definition

 An unpleasant sensation caused by

noxious stimulation of the sensory
nerve endings (Mosby’s Medical
Dictionary)
 It is a subjective feeling and an
individual response to the cause
 Can be influenced by several factors
like emotional state, cultural
background, etc.
 It may be… mild or severe, chronic,
acute, lancinating, burning, dull or
sharp, precisely or poorly localized,
or referred
 The neuronal basis of pain
-Pain receptors = nociceptors (Latin nocere, ‘to hurt’)
-Pain signal is transmitted through: A-delta (quick
response) & C- fibers

FIGURE 10.1 (A) Arrangement for transcutaneous nerve recording. (B) In the painful
stimulus range, the axons of thermoreceptors fire action potentials at the same rate as
at lower temperatures; the number and frequency of action potential discharge in the
nociceptive axon, however, continue to increase. (Note that 43°C is the approximate
threshold for pain.)
 First and Second Pain
-1st pain = transmitted though A-delta fiber; responsible for:
sharp pain
-2nd pain = transmitted though C fibers; responsible for:
dull, burning & long lasting senstation
myelinated
Myelinated Unmyelinated
unmyelinated

FIGURE 10.2  First and second pain. Pain can be separated into an early perception
of sharp pain and a later sensation that is described as having a duller, burning quality.
(A) First and second pain, as these sensations are called, are carried by different
axons, as can be shown by (B) the selective blockade of the more rapidly conducting
myelinated axons that carry the sensation of first pain, or (C) blockade of the more
slowly conducting C fibers that carry the sensation of second pain. (After Fields, 1990.) 5
 FIGURE 10.3  The anterolateral system (Part 1)

Pain travels from pseudo unipolar

neuron (in DRG)  projection
neuron  higher centers

FIGURE 10.3  The anterolateral system. (A) Primary afferents in the dorsal root ganglia
send their axons via the dorsal roots to terminate in the dorsal horn of the spinal cord.
Afferents branch and course for several segments up and down the spinal cord in Lissauer’s
tract, giving rise to collateral branches that terminate in the dorsal horn. Second-order
neurons in the dorsal horn send their axons (black) across the midline to ascend to higher
levels in the anterolateral column of the spinal cord.
 FIGURE 10.3  The anterolateral system (Part 2)

Dorsal Horn of
spinal cord

Second order
neurons
Rexed’s laminae

FIGURE 10.3  The anterolateral system. (B) C-fiber afferents terminate in

Rexed’s laminae I & II of the dorsal horn, while A-delta fibers terminate in
laminae I and V. The axons of second order neurons in laminae I and V cross
the midline and ascend to higher centers.
 Referred Pain
Definition: Pain at a site other than its actual source. Pain that arises
from damage to visceral organs is often misperceived as coming from a
somatic location (ex. Skin)

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 Referred Pain Wide-dynamic
Wamic-range
neurons
range neurons

 A subset of lamina V neurons

receive converging inputs from
both:
Nociceptive and non-nociceptive
(AB
ociceptive
= touch) afferents (Aβ = touch)

 These neurons are called:

 wide-dynamic-range neurons

 Wide-dynamic-range neurons
receive sensory input from both
visceral organs and skin areas
 Anterolateral
System
3 neuron system:
- first synapse made in
dorsal root of SC
(projection neuron)
- Crosses over/dessucation
at level of entry of SC
- Goes anteriorly and
laterally into SC
- 2nd synapse: dorsal
column medial lemniscus
system (thalamus 
Somatosensory cortex)

FIGURE 10.6 
Discriminative pain
pathways. Comparison of
the pathways mediating the FYOK
discriminative aspects of
pain and temperature for (A)
the body and (B) the face.
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 Parallel Pain Pathways
FYOK

Sensory discriminative:
Information on:
 Location, intensity
and quality of pain
(related to A-delta
fibers)

Affective-motivational:
 Unpleasant feeling,
fear, anxiety
 Autonomic activation

FIGURE 10.5  Two distinct aspects of the experience of pain. The anterolateral system
supplies information to different structures in the brainstem and forebrain that contribute to
different aspects of the experience of pain. The spinothalamic tract (left of dashed line)
conveys signals that mediate the sensory discrimination of first pain. The affective and
motivational aspects of second pain are mediated by complex pathways that reach
integrative centers in the limbic forebrain.
 Pain and temp enter SC
SPINAL CORD Right Left on R side and crosses
over to other side  have
At level of lesion on L side so will not
lesion: lose reach brain
sensation of
temp. & pain
on opposite
side and lose
proprioception
& touch on
same side of
lesion

FIGURE 10.4  Nociceptive and mechanosensory pathways. As diagrammed here, the

anterolateral system (blue) crosses and ascends in the contralateral anterolateral
column of the spinal cord, while the dorsal column–medial leminiscal system (red)
ascends in the ipsilateral dorsal column. A lesion restricted to the left half of the spinal
cord results in dissociated sensory loss and mechanosensory deficits on the left half of
the body, with pain and temperature deficits experienced on the right.
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Spinal Right Left
Cord

FIGURE 10.4  Nociceptive and mechanosensory pathways. As diagrammed here, the

anterolateral system (blue) crosses and ascends in the contralateral anterolateral column
of the spinal cord, while the dorsal column–medial leminiscal system (red) ascends in the
ipsilateral dorsal column. A lesion restricted to the left half of the spinal cord results in
dissociated sensory loss and mechanosensory deficits on the left half of the body, with pain
and temperature deficits experienced on the right.
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Peripheral Sentization No nociceptor = no pain
 Free nerve endings
 3 branches that go through the
dorsal horn of SC to synapse with
dorsal projection
Role: Where is the
nociceptor?
 Promote the injured area and
promote healing (hyperalgia)

 Guard against infection by

means of local effects such as
increased blood flow and the
migration of white blood cells to
the site

FIGURE 10.7  Inflammatory response to

tissue damage. Substances released by
damaged tissues augment the response of
nociceptive fibers.  

Main NT for pain = substance P

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Central Sensitization in Chronic Pain
 What is it?
 Increase in the excitability of
neurons in the dorsal horn of
the spinal cord following high
levels of activity in the
nociceptive afferents  Decreased threshold
for activating pain system
 When?
 After repeated stimulation over a
long period of time (weeks to
months)
 Consequence?
 Allodynia: induction of pain by a
normally innocuous (inoffensive)
stimulus
 Mechanism?
 Long term potentiation
(synaptic plasticity)
 Phantom Limbs & Phantom Pain 16

• IIlusion that the missing limb is still present

• 70% of people who lose a limb experience a phantom limb
• Phantom limb is not only for all legs and arms:
• Phantom breasts after mastectomy
• Phantom genitalia after castration
• Phantom to entire lower body after SCI
• Pain after amputation is usually more severe than before

CLINICAL APPLICATIONS
Phantom Limbs and Phantom
Pain
(A) Drawings of phantom arms and
legs, based on patients’ reports.
The phantom is indicated by a
dashed line, with the colored
regions showing the most vividly
experienced parts.
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Phantom Limbs & Phantom Pain

• Functional reorganization of somatosensory cortex (map)
• Neurons lost their original inputs from remote limb
• Tactile stimulation of other body parts

CLINICAL APPLICATIONS Phantom Limbs

and Phantom Pain
(B) Illustration of the mirror box designed by
Ramachandran to relieve phantom pain with
upper limb loss. The subject views his intact limb
and its reflection in a mirror while commanding
symmetrical movements of the remaining hand
and the corresponding phantom. For some
subjects, this experience immediately produces
mobility of the phantom with a remarkable
degree of relief from pain sensation. *need to focus
on the limb in
the mirror
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Mirror Therapy
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Placebo Effect
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Placebo Effect
 Placebo = Latin for “I will please”
o effect
Is the a true
placebo effect a truephysiological mechanism
physiological mechanism or it by
or is it only imagined is
the patients?
only imagined by the patients?

Classic Study:
 Medical students were given one
of the 2 pills: one said to be a
sedative and the other a
stimulant; both pills = fake!
 Sedative = 2/3 felt drowsy
 Stimulant = majority less tired

o 1/3 of both groups = headaches, dizziness, tingling

extremities, staggering gait
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Placebo Effect
Is the place
placebo effect real from a physiological standpoint?
 Imaging studies after the
administration of a placebo analgesic
pill (or “fake” pill) =

Activation of endogenous opioid

receptors in cortical and subcortical
regions

 This placebo effect was blocked by

naxolone, a competitive antagonist of
opioid receptors
 The placebo effect can contribute to
the efficacy of all medical treatments
and may explain the results obtain in
non-conventional therapies (eg:
hypnosis, homeopathy)
Effects of pain and placebo on the
activation of-opioid receptor-mediated
neurotransmission. Significant effects of
placebo on the activation of the opioid
system were detected in the left
dorsolateral prefrontal cortex, rostral
anterior cingulate and right anterior
insula. Zubieta et al. 2005
 Pain Inhibition Systems
 Level 5: ↓ nociceptive info by (figure not from texbook;
expectations, excitement, related to Fig 10.8)
distraction, placebos 5 levels:

 Level 4: ↓ nociceptive info by

hormonal endorphins 
decreases amount of
nociceptive signal to
decrease pain

 Level 3: ↓ nociceptive info by

the release of serotonin + ↓
substance P  brain stem
level (Raphe nuclei activated
& shuts down projection
neuron in dorsal horn of SC)

 Level 2: ↓ nociceptive info

through cutaneous
stimulation (TENS)  SC
level, right after synapse
with a-delta & C-fibers

 Level 1: ↓ prostaglandins by
analgesics (aspirin) 
decrease nociceptive signal
 Gate Control Theory
The gate control
theory of pain asserts
that non-painful input
closes the nerve
"gates" to painful
input, which prevents
pain sensation from
traveling to the central
-
nervous system.

Ex: rubbing or
massaging an injured or
a painful area =
Recruitment of AB fibers
= inhibit projection FIGURE 10.8  Descending systems modulate the transmission of ascending
pain signals (Part 2)
neuron in pain pathway. - non-painful input stimulates the nerve  AB fibers touch (tingling
Same mechanism with sensations) & activates inhibitory interneurons  projection neuron
TENS for pain that decreases nociceptive signal
- Release of Cl  postsynaptic potential more negative & less AP
travelling through projection neuron to brain where it is interpreted
as pain
Error in the textbook in FIGURE 10.8
Pain Measurement

Used in
children
 McGill Pain Time component
Questionnaire
 Most used scale

INSTRUCTIONS:
For each row, place an "X" next
to the one word that best
describes your pain. Choose no
more than one word in each row.
If no words in a row describe
your pain, then do not choose
any words in that row.

For each row, words are placed in

ascending order: from less severe
to more severe Draw where pain is on the body

The descriptors fall into 4 major

groups: #1 pain questionnaire in the
medical/rehab community
1- Sensory (items 1-10) across the world
2- Affective (items 11-15)
3- Evaluative (item 16)
4- Misc. (items 17-20)
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Nociceptive Signal Processed at the Brain Level

 In a pain experience, many parts of the brain are
involved simultaneously
FYOK
 These brain parts
included clusters of
nodes used for:
 Sensation (SSC)
 Movement (flashing with
pain)
 Emotions
 Memory

 Persistent pain (or

chronic pain): some of
these nodes are
‘hijacked’ or even
enslaved to the pain
experience Explain Pain Second Edition, David S. Butler & G. Lorimer Moseley
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Tissues Healing Process

 Pain should diminish as the tissues heal
 Pain associated with nerve damage sometimes persists

 Common Symptoms
Associated with
Peripheral Nerve Pain:
 Pins and needles
 Burning pain
 Pain at night, especially
in hands and feet
Explain Pain Second Edition, David S. Butler & G. Lorimer Moseley

 Movement or even sustained posture may ignite an injured

nerve: it just keeps ringing like a car alarm!
 Stress makes it worse (pain vigilance)
 Overtime = Lead to altered central nervous system alarms
 Sensitization of pain pathways
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Toughts & Beliefs are Nerve Impulses Too
All of these ‘thoughts viruses’ below are common in people with
persistent pain who don’t understand the physiology of pain:
They are known to cause & enhance low back pain (and probably pain
experience anywhere else in the body)

FYOK

Explain Pain Second Edition, David S. Butler & G. Lorimer Moseley

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Relationship between Pain and Activity Level
Passive Copers
Natural response:
Stop the activity
when pain begins

Over time the amount

of activity at which
pain is experienced
Figure. Example of activities:
REDUCES Cycling, walking, using a computer, attending a lengthy
function etc.

Disability, disuse, and  As activity decreases, pain onset increases

probably depression  Do their best but limit activity level with pain

Descent into Chronicity: More common in people who are afraid of

pain & re-injuring tissues (passive copers)
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Relationship between Pain and Activity Level
High Achievers:
 Increase in activity up to flare-up
 System becomes more sensitized as flare-ups occur
 Boom-Bust Pattern:
more often
Pain comes on but you
persevere, you tolerate it
as much as you can, and
try to ignore it, keep
going, distracting yourself
(‘boom’) until suddenly
your pain is unbearable
and you ‘bust’
Figure. Example of activities:
Cycling, walking, using a computer, attending a lengthy
function etc.

Consequence: More Common in: End-Result:

Clients are exhausted +
________________ Perfectionists, high
________________ ________________
Activity extremely low
flare up during days or
______________ achievers,
______________ ______________
because pain has
even weeks become the master
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Pacing and Graded Exposure

1. Decide what you want to The art of graded exposure and pacing
do more: ex. Walking, Scoring some brain triumphs
cycling, working
2. Find your baseline
 How long can I walk
before a flare-up?
3. Plan your progression:
plan to walk slightly
further each day for the
next week (30s increase)
4. Don’t flare-up (but don’t
freak out if you do!)
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Find your baseline

How long can I walk before a flare-up?
I can walk for 30 min but I pay for it the next day
Can I walk walk for 20 min without flaring up?
No, I will still pay for it
Can I walk walk for 10 min without flaring up?
Probably not – definitively not up hills
5 min on a flat surface?
Probably
3 min on a flat surface?
Definitively = your baseline would be 3 min (flat surface)
 Pacing and Graded Exposure
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Before injury: After injury:

- pain level tells you when you reach your - Pain level & tissue
danger zone tolerance level lower
- Tissue tolerance line = where you get injured

Recalibration: levels moves up very slowly

And now plan your ‘training’. Let’s walk through the 1 st of the small mountains in the figure below
A. Starting below the B. The flare-up line will C. The protect by pain line D. The tissue tolerance line
flare-up line, gradually ↑ slowly lift along with your will slowly lift – the will also lift – this is one of
your activity, planning training level (this is sensitivity of the system ↓ the beautiful properties of
steps in advance: ‘always because you are training highly adaptable beings –
do more than you did your brain, ↓ the perceived the tissues get stronger,
yesterday, but not much threat fitter, better controlled
more’
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Understanding Pain