The Gate Theory of Pain

1. THE GATE THEORY OF
PAIN
Ade Wijaya, MD – May
2019

2. INTRODUCTION
• The Gate Theory of Pain, published by Ronald Melzack and Patrick
Wall in Science in 1965
• A mechanism for coding the nociceptive component of cutaneous
sensory input
Mendell LM. Constructing and deconstructing the gate theory of pain. PAIN®. 2014 Feb 1;155(2):210-6.

3. INHIBITION OF CUTANEOUS INPUT TO THE
SPINAL CORD
• Large fibers normally inhibit the effects of small fibers. The balance
between the large and small fiber input was a major factor in
determining the painfulness of a stimulus.
• Long lasting presynaptic inhibition of input to motor neurons elicited
by volleys in large afferent fibers
Noordenbos W. Pain. Elsevier, Amsterdam; 1959.
Frank K, Fuortes MGF. Presynaptic and postsynaptic inhibition of monosynaptic reflexes. Fed. Proc.

4. CELLS RESPONSIBLE FOR
GENERATING PRESYNAPTIC
INHIBITION OF CUTANEOUS SENSORY
FIBERS• An important component of the Gate Hypothesis was the
suggestion by Wall that cells of the substantia gelatinosa
(SG) were responsible for the presynaptic effects
Szentagothai J. Neuronal and synaptic arrangement in the substantia gelatinosa rolandi. J Comp Neurol.
Wall PD. The origin of a spinal-cord slow potential. J Physiol. 1962;164:508–526.
Wall PD. Presynaptic Control of Impulses at The First Central Synapse in The Cutaneous Pathway. Prog Brain Res. 1964;12:92–118

5. THE GATE THEORY OF PAIN MODEL
Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–979.

6. TESTS OF CLOSING AND OPENING
THE GATE
• High frequency stimulation of the large fibers in that nerve
(Transcutaneous Nerve Electrical Stimulation- TENS) produced
tingling referred to the distribution of that nerve and relief of the pain
for the duration of the stimulation, and for 30 min after cessation of
the stimulation
• Reappearance of pain was attributed to gradual reopening the gate
by ongoing small fiber activity which was less intense in cases where
peripheral nerves had been damaged and therefore took longer to be
re-established
Wall PD, Sweet WH. Temporary abolition of pain in man. Science. 1967;155:108–109.

7. WINDUP PHENOMENON
• Repetitive discharge of spinal neurons exhibited a phenomenon
called windup
• It became more prolonged in response to each successive C-fiber
stimulus if it occurred within 4 seconds of the preceding one  due
to the release of peptides by certain small diameter afferents which
prolongs the synaptic potential thus allowing temporal summation
over a period of seconds
• This depolarization activates NMDA receptors whose blockade
abolishes windup without eliminating the response to C-fiber
stimulation
• Windup is an early event in a process leading to central sensitization
Kumazawa T, Perl ER. Excitation of marginal and substantia gelatinosa neurons in the primate spinal cord: indications of their place in dorsal horn functional organization. J Comp Neurol.
1978;177:417–434
Mendell LM. Physiological properties of unmyelinated projection to the spinal cord. Exp. Neurol.
Mendell LM, Wall PD. Response of single dorsal cord cells to peripheral cutaneous unmyelinated fibers. Nature.
Woolf CJ. Windup and central sensitization are not equivalent. Pain. 1996;66:105–108.

8. NOCICEPTORS
• Receptors activated by stimuli that were potentially damaging to the
tissue in which they were embedded
• Nociceptors were later found to have important physiological
properties such as sensitization, and to project into the superficial
dorsal horn where they synapse upon a population of cells called
marginal cells that respond exclusively to noxious stimuli
• These cells in the marginal zone were found to contribute to the
spinothalamic tract which gave them access to forebrain structures
and thus presumably to conscious sensation.
• A population of nociceptors was also observed to be peptidergic and
thus able to promote Windup
Mendell LM. Constructing and deconstructing the gate theory of pain. PAIN®. 2014 Feb 1;155(2):210-6.

9. SUMMARY
• The Gate Theory of Pain was formulated using available physiological
observations to explain certain behavioral and psychophysical
observations related to pain
• A mechanism for coding the nociceptive component of cutaneous
sensory input