supplement to Journal of the association of physicians of india Published on 1st of every month 1st february, 2015
Pathophysiology of Pain
Vikram A Londhey*
*
Associate Professor,
Department of Medicine, TNMC
and BYL Nair Ch Hospital,
Mumbai 400 008; Visiting
Consultant Rheumatologist,
Seven Hills Hospital, Marol
Maroshi, Mumbai
W hy so much pain and suffering
in this world? 1 What a pain
he or she is! The word pain is used in
various contexts. Most often it is linked to
emotions of grief, sorrow and suffering.
The word pain comes from the Latin
word poena meaning a fine, a penalty.
Pain as the fifth vital sign has been
introduced by the American Pain Society
in 1996. 2 According to the International
Association for the Study of Pain(IASP)
it is defined as Pain is an unpleasant
sensory and emotional experience arising
from actual or potential tissue damage.3
It is a sensation that can range from
mild, localized discomfort to agony.
Pain has both physical and emotional
components. The physical part of pain
results from nerve stimulation. Pain
may be contained to a discrete area, as
in an injury, or it can be more diffuse,
as in disorders like fibromyalgia. Pain is
also a term specifically used to denote
a painful uterine contraction occurring
in childbirth known as labour pains.
With this background, it is necessary
to have the basic understanding of the
neuroanatomy and physiology of pain to
tackle it in a reasonable way in the era of
evidence- based- medicine.
Hence, i am sure all the readers of this
issue will recollect their 1 st MBBS days as
a medical student, when all of us have
been trained in physiology of pain. Lets
go into flash-back and recollect a few of
those aspects.
Types of Pain, its Receptors
And Stimuli4
Most of the body ailments cause pain.
The ability to diagnose different clinical
conditions depends on a clinicians
knowledge of different types of pain.
Pain is a protective mechanism. It occurs
when tissues are damaged and there is a
natural reaction from the individual to
remove pain stimulus. The pain receptors
are free nerve endings. They are present
in superficial layers of skin, periosteum,
arterial walls, joint surfaces, falx cerebri
and the tentorium. The pain receptors
are stimulated by mechanical, thermal
and chemical stimuli. Physiologically
pain has been classified into 2 types:
fast pain and slow pain. Fast pain is
felt within 0.1sec. It is also described as
sharp, acute, electric or pricking pain. It
is commonly felt in superficial tissues,
seldom in deeper tissues. Fast pain
pathway is stimulated by mechanical
or thermal pain stimuli and carried by
A fibers at velocities between 6 and
30m/sec. Sharp pain makes the person
aware of the damaging influence and
react immediately to remove himself or
herself from the stimulus. Slow pain is
also called burning, aching, throbbing,
gnawing, nauseating or chronic pain.
It is present in skin as well as deep
tissues. The slow pain pathway is mainly
stimulated by chemical stimuli (but also
by mechanical and thermal) and carried
by type C fibers at velocities between 0.5
and 2 m/sec. Chemicals like bradykinin,
serotonin, histamine, potassium ions,
acids, acetylcholine and proteolytic
enzymes are responsible to generate
pain. Prostaglandins and substance P
enhance the sensitivity of the nerve
endings without directly exciting them.
The pain receptors are non-adapting
and hence differ from other receptors
of sensations. They have the unique
property of hyperalgesia. The factors
causing pain are heat, lactic acidosis
resulting from tissue ischemia, tissue
contusion, bacterial infection; muscle
spasm due to stimulation of mechanical
receptors directly and indirectly by
compression of blood vessels thereby
causing ischaemia.
Pain Pathways4
On entering the spinal cord from
dorsal spinal roots, the pain fibers
terminate on relay neurons in dorsal
horns. Further, they are carried to the
brain by the neospinothalamic tract or
the paleospinothalamic tract.
6 supplement to Journal of the association of physicians of india Published on 1st of every month 1st february, 2015

Somato Periaqueductal gray

region around Ventrolateral
Sensory aqueduct of Sylvius nuclei of thalamus
Ventro Posterior Cortex
Tectal Reticular
Basal Nuclues area of formation of medulla,
Reticular formation mesencephalon
Nuclei of pons and mesencephalon
of Thalamus
Thalamus

Antero Anterolateral
lateral columns
Columns (Ascending Tracts)
(Ascending
Tracts)

Cross over
to opp. side

Cross
over Spinal Dorsal root ganglion Substantia
Cord Gelatinosa
to opp. side
Slow
C fibers
pain

Free Nerve Endings

Dorsal root Spinal Fig. 1 : Paleospinothalamic tract

ganglion cord
Fast A paleospinothalamic tract terminates in brain stemin
Pain Fibers
Free Nerve Endings
Fig. 1 : Neospinothalamic tract
The Neospinothalamic tract4
A fibers transmit mainly mechanical and thermal
pain, terminate in the dorsal horns, cross over to the
opposite side of the cord and continue upwards to the
brain as anterolateral columns. Most fibers terminate
in the ventrobasal or posterior nuclei of the thalamus;
few fibers terminate in the reticular areas. Signals are
also sent to the somatosensory cortex. Glutamate is
the neurotransmitter secreted in the spinal cord at A
fibers (Figure 1).
The Paleospinothalamic tract4
The C fibers which carry slow pain terminate in
the substantia gelatinosa of dorsal horns in spinal
cord. They also cross over to the opposite side and
continue as anterolateral ascending tracts. The
one of the following areas:
1. R e t i c u l a r n u c l e i o f m e d u l l a , p o n s a n d
mesencephalon.
2. Tectal area of mesencephalon deep.10-25% of the
fibers pass to the thalamus.
3. Periaqueductal gray region surrounding the
aqueduct of Sylvius.
The signals are relayed into the intralaminal and
ventrolateral nuclei of thalamus, hypothalamus and
basal regions of brain. The pain carried by slow
chronic pathway is poorly localised. Substance P is the
neurotransmitter concerned with slow pain (Figure 2).
Higher Centres for Pain4
Reticular formation, thalamus and lower brain
centres cause conscious perception of pain. But the
cerebral cortex is responsible for interpreting the
quality of pain. The pain signals have a strong effect
on the arousal system which explains the disturbed
sleep or insomnia in a person experiencing pain.
supplement to Journal of the association of physicians of india Published on 1st of every month 1st february, 2015 7
Periaqueductal gray and periventricular areas of
mesencephalon and upper pons surrounding the
aqueduct of Sylvius and portions of 3 rd and 4 th
ventricles.
Raphe Magnus nucleus in lower pons and Medulla
and nucleus reticularis paragigantocellularis(in
lateral medulla)
Through Dorsolateral
columns to spinal cord
Pain inhibitory complex in dorsal horns of spinal
cord.
Fig. 3 : Analgesia system
Analgesia System4
The pain threshold varies from person to person
and the reaction to pain is highly variable. There is a
natural inbuilt system of the brain to suppress input
of pain signals called analgesia system. The analgesia
system is diagrammatically represented in Figure 3.
The neurotransmitters released by the analgesia
system are enkephalin and serotonin. Enkephalins
inhibit pre and post synaptic C fibers and A fibers
when they synapse in dorsal horns, thus blocking
the pain signals at initial entry into the spinal cord.
Activation of the analgesia system by nervous signals
entering the periaqueductal gray and periventricular
areas or inactivation of pain pathways by analgesics
almost totally suppress the pain signals entering
through the peripheral nerves.
The large type A sensory fibres responsible for
carrying touch sensation can depress transmission
of pain signals from the same area. Hence, when
stimulated simultaneously, there is suppression of
pain. This is the rationale and the basis of pain relief
by applying liniments, massage, acupuncture and
acupressure.
Visceral pain and Concept of Referred
Pain4
The viscera in the different parts of the body also
have pain receptors. The visceral pain differs from
the surface pain. The visceral pain in the thorax and
abdominal cavity is transmitted through the C fibers.
The visceral pain fibers synapse in the spinal cord on
same second order neurons that receive pain signals
from the skin fibers. Hence pain in the remote or deep
seated organs is experienced in the skin which have
a common embryological dermatomal origin.This is
called as referred pain. The stimuli for visceral pain
also include ischaemia, smooth muscle spasm, excess
distension of hollow organs, action of proteolytic
enzymes and stretching of surrounding connective
tissue.
Coming back to the present day from our flash-back,
this special issue of JAPI Understanding Pain-The 5 th
Vital Sign discusses elaborately the ways of assessing
pain, managing acute and chronic pain. There are also
practical tips on evaluation of the back pain and the
various interventions necessary for pain management.
At times, it may be challenging to all the clinicians
when the pain in psychogenic in nature; hence the
differential diagnosis and treatment of psychogenic
pain disorder has been discussed in this special issue.
Managing pain is a team-work and hence beyond the
patient and the clinician, the paramedics particularly
the physiotherapist has a major role to play. The issue
has been well written by a series of authors well known
in their fields for the management of pain. I am quiet
confident that this special issue on pain would act as a
Bible for all the practioners and the resident doctors
of various specialities in making our patients free from
pain i.e Aah se Aha tak!.
References
1. Indeed, one of the greatest Christian theologians of the last century
remarked, The fact of suffering undoubtedly constitutes the single
greatest challenge to the Christian faith. John Stott, The Cross of
Christ(Downers Grove, IL: IVP Books, 2006), 303.
2. Preeti Doshi. How to assess Pain? JAPI 2015;63;Suppl.5-11.
3. International Association for the Study of Pain: Pain Definition. Bonica
JJ. The need of a Taxonomy. Pain 1979;6:247-8.
4. John.E.Hall. Chapter 48 Somatic Sensations II. Pain, Headache &
Thermal Sensations. Guyton and Hall Textbook of Physiology Twelth
Edition. In Ed. John E. Hall Elsevier Saunders 2011;583-593.