neurophysiology of pain
TRANSCRIPT
GOOD MORNING
NEUROPHYSIOLOGY OF PAIN
PRESENTED BYDR.RAVNEET KOUR
OUTLINE Introduction and definition Types of pain Pain receptors Chemical mediators of pain Dual nature of pain Theories of pain perception Physiology of dental pain Pain assessment scales
REFERENCES Frederick A. Curro PAIN DCNA 1978;22(1):1-173
GUYTON . Textbook of Medical Physiology. 11th edition : Pg no. 588-606
JOHN I .INGLE: Endodontics. 5THed: Pg No. 287-299
A .DRAY British journal of anesthesia 1995;75:125-131
Indian J Physiol Pharmacol NEUROPHYSIOLOGY OF PAIN : INSIGHT TO OROFACIAL PAIN O. P. TANDON, V. MALHOTRA, S. TANDON AND I. D’SILVA 2003;47 (3):247–269
Carl L von Baeyer, PhD RDPsych Children’s self-reports of pain
intensity: Scale selection, limitations and interpretation.
Pain is perfect misery, the worst of evils; and excessive, overturns all patience.
–John Milton, Paradise Lost
Pain is not a simple sensation but rather a complex neurobehavioral event involving at least two components.
First is an individual’s discernment or perception of the stimulation of specialized nerve endings designed to transmit information concerning potential or actual tissue damage (nociception).
Second is the individual’s reaction to this perceived sensation (pain behaviour).
Pain is difficult to define, quantify, and understand is reflected in the numerous ways in which it has been described
Dorland’s Medical Dictionary defines pain as “a more or less localized sensation of discomfort, distress, or agony resulting from the stimulation of specialized nerve endings.”
DEFINITION OF PAIN International Association for the
Study of Pain (IASP) “An unpleasant sensory and emotional experience associated
with actual or potential tissue damage, or described in terms of such damage.”
Pain is always subjective.
Each individual learns the application of the word through experiences related to injury in early life.
It is unquestionably a sensation in a part of the body, but it is also always unpleasant and therefore also an emotional experience.
Psychological reasons for pain perception.
Difficult to make distinction based on subjective report.
Accept as pain even if only a psychological basis.
TYPES OF PAIN (ACC. TO GUYTON) FAST PAIN SLOW PAIN
It can occur both in the skin and in almost any deep tissue or organ
Slow pain also goes by many names, such as slow burning pain, aching pain,throbbing pain, nauseous pain, and chronic pain.
generally elicited by chemical types of stimuli
• Not felt in deeper tissues
•Fast pain is also described by many alternative names, such as sharp pain, pricking pain, acute pain, and electric pain.
• generally elicited by mechanical & thermal types of stimuli.
PAIN RECEPTORS The pain receptors in the skin and other tissues are all free
nerve endings. The receptors which mediate pain are called NOCICEPTORS.
small unmyelinated ‘C’ fibres or myelinated ‘A δ’ afferent neurons.
widespread in the superficial layers of the skin as well as in certain internal tissues, such as the periosteum, the arterial walls, the joint surfaces, and the falx and tentorium in the cranial vault.
COMPONENTS OF A TYPICAL CUTANEOUS NERVE
TYPES OF STIMULI EXCITE PAIN RECEPTORS
Pain can be elicited by multiple types of stimuli. They are classified as mechanical, thermal, and chemical pain
stimuli.
fast pain is elicited by the mechanical and thermal types of stimuli
slow pain can be elicited by all three types.
Mechanical stimulation due to: Excessive pressure or tension on nerves. E.g.- a blow on the head, pulling of hair etc. Compression of nerves by tumour.
Thermal stimulation- Raising skin temperature above 45ºC or exposure to cold (0ºC) is painful.
Chemical stimulation by irritant chemicals such as histamine, kinins & prostaglandins released from damaged tissue.
CHEMICAL PAIN MEDIATORS Nociceptors
sensitized byNociceptors activated by Bradykinin Histamine Serotonin Increased potassium
concentration Proteolytic enzymes Acids Acetlycholine
Prostaglandins Substance P Interleukins Leukotrienes
CHEMICAL MEDIATORRS A variety of chemical mediators are
able to alter the function of peripheral afferent fibres.
Afferent fibre may be unresponsive even to intense stimuli, but are highly responsive when stimuli induced by inflammation mediators.
Some chemicals may induce influence on function of afferent fibres.
Sensory fibres metabolism and activity is greatly altered by a variety of mediators produced by tissue injury, inflammation.
Substances produced by damaged tissue, afferent fibres, immune cells.
Some mediators like protons, 5-hydroxytryptamine can act directly on membrane ion channel protein to change permeability and cell excitability.
CHEMICAL MEDIATORS OF PAIN
Sensory neuron takes information ↓Send information to motor neuron ↓Tissue damage will lead to release of
chemicals like potassium ions, histamine etc.
↓ conduction of these signals in special
nerve fibres Aδ and C fibre ↓Signals head to spinal cord and to brain
through spinothalmic pain pathway
Spinothalmic pain fibres runs up to the spinal cord though medulla, Pons, midbrain upto thalamus.
↓Sensory nerves in spinal cord are
grouped together in dorsal root ganglion.
↓Signals sent from thalamus upward to
primary sensory cortex. ↓
An area in spinal cord called dorsal horn conduct nervous impulses to the brain and back down to spinal cord to area of injury.
Brain does not pass message of removing hand from spike, dorsal horn of the spinal cord sent it to muscle of hand to withdraw quickly.
Further thalamus send signal to areas controlling blood pressure, heart rate, breathing and emotions.
One chemical that seems to be more painful than others is bradykinin.
Increase in potassium ion concentration and proteolytic enzymes that directly attack the nerve endings and excite pain by making the nerve membranes more permeable to ions.
Variety of substance released during tissue damage to cells these have a profound effect on the afferent fibres.
Damaged tissue or blood cells release the polypeptide bradykinin (BK), potassium, histamine, serotonin, and arachidonic acid.
Arachidonic acid is processed by two different enzyme systems to produce prostaglandins and leukotrienes, which, along with BK, act as inflammatory mediators .
Bradykinin acts synergistically with these other chemicals to increase plasma extravasation and produce edema.
Plasma extravasation, in turn, replenishes the supply of inflammatory chemical mediators.
Tissue ischemia as a cause of pain
When blood flow to a tissue is blocked, tissue becomes painful within minutes.
Accumulation of large amounts of lactic acid in the tissue as a consequence of anaerobic metabolism.
It is also probable that other chemical agents, such as bradykinin and proteolytic enzymes, are formed in the tissues.
Muscle spasm as a cause of pain
Partially from the direct effect of muscle spasm in stimulating mechano sensitive pain receptors
Also result from the indirect effect of muscle spasm to compress the blood vessels and cause ischemia
DUAL NATURE OF PAIN
Pain has two components:
Pain perception
Pain reaction
Objective component of pain. Emotional experience to the perceived injury.
Physio-anatomic processImpulse is generated after application of adequate stimulus and is transmitted to the CNS.
Psycho physiological process and involves the cortex, hypothalamus & thalamus.
This aspect of pain is almost similar in all healthy individuals and varies little from day to day
Varies from individual to individual and also from day to day in the same person.
PAIN PERCEPTION PAIN REACTION
SENSORY THRESHOLD- defined as the lowest level of stimuli that will cause any sensation-the summation of large sensory fibers from receptors for touch, temperature & vibration.
PAIN THRESHOLD – As the stimulus is increased, the sensation becomes stronger until pain is perceived. This is pain threshold.
Fairly constant among individuals.
PAIN TOLERANCE / RESPONSE THRESHOLD
If the intensity of the stimulus is increased above pain threshold, a level of pain will be reached that the subject can no longer endure. This is pain tolerance or the response threshold.
At this point the individual makes an attempt to withdraw from the stimulus.
Range between the pain threshold and the response threshold is termed as a person’s tolerance to pain.
Fiber Diameter (µ)
Conduction velocity (m/s)
Function
A-alpha
A- beta
A-delta
A- gamma
B
C
6-20
5-12
1-4
3-6
< 3
0.4-1.0
30-120 (myelinated)
30-120
5-25
15-35
3-15 (myelinated)
0.7-2.0 (unmyelinated)
Motor, perception Motor, perception Pain, temperature, touch
Muscle tone
Various autonomic functions
Various autonomic functions; pain temperature, touch
THEORIES OF PAIN PERCEPTION Central Summation theory Livingstone,1943 Sensory-Interaction theory Noordenbos 1959 Gate Control Theory Ron Melzack and Patrick
Wall in 1965 Specificity theory 1980’s von Frey
SPECIFICITY THEORY: 1980’s von Frey Body has a separate sensory system for
perceiving pain just as it does for hearing and vision.
They Considered pain as an independent sensation, which respond to damage and send signal to the target centre in brain.
Free nerve endings are pain receptors. according to specificity theory says referred
pain require convergence of noxious input from different sites on neurons responding exclusively to noxious input .
MAJOR DEFICITS OF SPECIFICITY THEORY: Inability to explain some of the characteristics of clinical pain.
Hyperalgesic areas of skin following peripheral injury; cannot explain all pathologic pains produced by mild non-noxious stimuli.
The specificity theory also does not explain referred pain that can be triggered by mild innocuous stimulation of normal skin.
Also does not explain pain produced by mild stimulation of trigger zones in trigeminal neuralgia.
CENTRAL SUMMATION THEORY
Goldschieder 1894 The intense stimulation resulting from
the nerve and tissue damage activates fibres that project to neuron in spinal cord creating abnormal reverberating circuits with self- activating neurons.
Pain resulted when activity exceeded a critical level normally responsive to non-noxious stimuli.
Major deficit: the theory did not recognize the importance of receptor specialization to noxious stimuli.
Valuable contribution: its emphasis on central summation and convergence.
Summation theory proposes that pain is not a separate modality but results from overstimulation of other primary sensation.
SENSORY-INTERACTION THEORY Noordenbos 1959
Rapidly-conducting large fiber pathways inhibit activity in slowly conducting small fiber pathways that convey noxious information.
An increase in the ratio of large to small fiber activity results in more inhibition in nociceptive pathways and a decrease in pain.
Stressed the importance of multi synaptic afferent system in the spinal cord.
Hyperalgesia following peripheral nerve injury can be explained by a greater loss of large fibers than of smaller fibers.
GATE CONTROL THEORY
Ron Melzack and Patrick Wall in 1965
Combined the strengths of previous theories and added some of its own.
physical pain is not a direct result of activation of pain receptor neurons, but rather its perception is modulated by interaction between different neurons
Pain stimulation carried by small slow fibres that enter dorsal horn of spinal cord .
Cells which transmit signal from spinal cord to brain are called T-cells.
T-cells located on specific areas of spinal cord known as substantial gelatinosa
These cells can inhibit or allow communication into CNS .
e.g. large fibres can inhibit transmission from small fibres from communicating to brain, in this way large fibres create a hypothetical gate that opens and closes to pain stimulation.
The greater the level of pain the less adequate the gate in blocking the communication.
The basic points put forth by the theory are as follows:
there is a "gating system" in the central nervous system that opens and closes to let pain messages through to the brain or to block them
large diameter (Aβ) fibers activated by low threshold non-noxious stimuli, and small-diameter (Aδ + C) fibers activated in most cases by intense, noxious stimuli.
Activity in large fibers tends to inhibitt transmission (close the
gate) Small fiber activity tends to facilitate transmission (open the
gate).
Final response - depend on the net result of the initial input from all 3 systems
1) Large diameter fibers 2) Small diameter fibers 3) Central Control
Thin fibres activity impedes the inhibitory cells (allow the transmission cell to transmit signal)
Large diameter fibre activity excites the inhibitory cell (inhibiting transmission cell activity)
More the large fibre activity (touch, pressure) relative to thin fibre activity at inhibitory cells, less pain is felt.
MECHANISM OF GATE CONTROL THEORY
Processing of pain from the stimulation of primary afferent nociceptors to the subjective experience of pain can be divided into 4 steps
1) Transduction 2)Transmission
3) Modulation 4) Perception
(Fields H. Pain,1987)
PAIN PROCESSING
TRANSDUCTION Activation Of The Primary Afferent Nociceptor.
Can Be Activated By Intense Thermal & Mechanical Stimuli, Noxious Chemicals And Noxious Cold.
Also Activated By Stimulation From Endogenous Algesic Chemical Substances.
Bradykinin- inflammatory mediator
Increase plasma extravasation & produce edema. Replenished supply of inflammatory mediators
Causes sympathetic nerve terminal to release a prostaglandin.
Membrane lipids produce STERODIS ACT HERE
ARACHIDONIC ACID NSAIDS ACT HERE cyclooxygenase lipoxygenase
PROSTAGLANDINS LEUKOTRIENE B₄
PMLs 8R, 15S-diHETE acts on 15-Lipoxygenase product
acts onA-delta and C fibers
Pain due to a stimulus that does not normally provokepain(Allodynia) Increased pain from a stimulus that normally provokes pain(Hyperalgesia)
Allodynia is pain the arises from stimuli that do not normally evoke pain e.g. tactile or thermal stimuli becoming painful,this may be associated with nociceptive pain from sunburn or tissue injury.
TRANSMISSION the process by which peripheral nociceptive information is relayed to
the central nervous system.
The primary afferent nociceptor synapses with a second order pain transmission neuron in the dorsal horn of the spinal cord where a new action potential heads toward higher brain structures.
THE DUAL PATHWAY FOR TRANSMISSION OF SIGNALS
IN THE CENTRAL NERVOUS SYSTEM
a fast – sharp pathway
a slow – chronic pathway.
THE PERIPHERAL PAIN FIBERS – ‘FAST’ AND ‘SLOW’ FIBERS
FAST PAIN FIBERS SLOW PAIN FIBERS
fast sharp pain signals are elicited by either mechanical or thermal pain stimuli;
slow-chronic type of pain is elicited mostly by chemical stimuli but sometimes by persisting mechanical or thermal stimuli.
transmitted in the peripheral nerves by small type Aδ fibers
transmitted to the spinal cord by type C fibers
velocities between 6-30 m/s velocities between 0.5-2 m/s.
DUAL PAIN PATHWAYS IN THE CORD AND BRAIN STEM
THE NEOSPINOTHALAMIC TRACT
THE PALEOSPINOTHALAMIC TRACT
PROCESSING OF THE FAST SIGNALS NEOSPINOTHALAMIC TRACT
•Aδ fibers transmit fast pain
•Terminate in lamina I (lamina marginalis) of the dorsal horns of the spinal cord. Excite second-order neurons of the neospinothalamic tract.
PROCESSING OF THE FAST SIGNALS NEOSPINOTHALAMIC TRACT
These give rise to long fibers that cross immediately to the opposite side of the cord through the anterior commissure and then turn upwards, passing to the brain in the anterolateral columns.
TERMINATION OF THE FAST ACUTE PAIN PATHWAY IN THE BRAIN STEM AND THALAMUS
Most pass all the way to the thalamus without interruption, terminating in the ventrobasal.
From these thalamic areas the signals are transmitted to other basal areas of the brain as well as the somatosensory cortex.
CAPABILITY OF THE NERVOUS SYSTEM TO LOCALIZED FAST PAIN IN THE BODY;
Fast pain can be localized much more exactly in different parts of the body.
However, when only pain receptors are stimulated, without the simultaneous stimulation of tactile receptor, even fast pain may be poorly localized.
GLUTAMATE, THE PROBABLE NEUROTRANSMITTER OF THE TYPE Aδ FAST PAIN FIBERS
most widely used excitatory transmitters in the CNS, usually have a duration of action lasting for only a few milliseconds
PROCESSING OF SLOW SIGNALS PALEOSPINOTHALAMIC PATHWAY The type C – fibers terminate almost entirely in the laminae II
& III of the dorsal horns( substantia gelatinosa). Most of the signals then pass through one or more additional
short fiber neurons eventually terminating mainly in Lamina V.
Here the last neuron in the series gives rise to long axons that join the fibers from the fast pain pathway, passing first through the anterior commissure to the opposite side of the cord, then upward to the brain in the anterolateral pathway.
MODULATION Refers to mechanisms by which the transmission of noxious
information to the brain is reduced.
THE PAIN SUPPRESSION (ANALGESIA) SYSTEM IN THE BRAIN AND SPINAL CORD:
The degree to which each person reacts to pain varies tremendously.
This results partly from the capability of the brain itself to control the degree of input of pain signals to nervous system by activating of a pain control system called an analgesia system (descending inhibitory systems)
Inhibitory Transmitter substances – norepinephrine (NE)& Serotonin.
An endogenous opioid system for pain modulation also exists. Endogenous opioid peptides are naturally occurring that are implicated in pain suppression and modulation because they are present in large quantities in the area of the brain associated with there activities (subnucleus caudalis and the substantis gelatinosa of the spinal cord)
Activity in the pain modulation system means that there is less activity in the pain transmission pathway in response to noxious stimulation.
PAIN PERCEPTION MRI studies have demonstrated the involvement of the thalamus
& multiple cortical areas in the perception of pain
How and where the brain perceives pain is still under investigation.
MECHANISM OF REFFERED PAIN Referred pain originates at one site (e.g. mandibular first
molar) and is experienced at another site (e.g. the ear).
When pain is referred to another part of the body, the site of referral is usually a part of the body that develops from the same embryological segment or dermatome, as the affected source of the pain.
referred pain thus helps in making correct diagnosis of the diseased e.g. Gall bladder pain is referred to right shoulder tip and cardiac pain to left shoulder and upper arm.
The two most popular theories to explain the mechanism of referred pain are;
convergence-projection convergence-facilitation
CONVERGENCE-PROJECTION THEORY: Most popular theory
Primary afferent nociceptors from both visceral and cutaneous neurons often converge onto the same second order pain transmission neuron in the spinal cord
The brain, having more awareness of cutaneous than of visceral structures through past experience, interprets the pain as coming from the regions subserved by the cutaneous afferent fibers.
VISCERAL AFFERENT NOCICEPTORS (S) CONVERGE ON THE SAME PAIN-PROJECTION NEURONS AS THE AFFERENTS FROM THE SOMATIC STRUCTURES IN WHICH THE PAIN IS PERCEIVED
CONVERGENCE-FACILITATION THEORY Similar to the theory above, except that the nociceptive input
from the deeper structures causes the resting activity of the second order pain transmission neuron in the spinal cord to increase or be “facilitated”
The resting activity is normally created by impulse from the cutaneous afferents.
“facilitation” from the deeper nociceptive impulses causes the pain to be perceived in the area that creates the normal, resting background activity.
NEUROPHYSIOLOGY OF DENTAL PAIN Face is considered as a mirror of mind- Inward
events, emotions, behaviours are reflected on facial expressions.
The cortex is also a mirror image to the body. It reflects the body image and perceives what the
body experiences. The cortical homunculus of the body has wide representation for orofacial area as compared to other parts.
Pain in dentistry provides information about the noxious stimuli-characterised by quality, intensity, location and duration, pain from other regions may not reflect that.
the most important factor affecting reaction to pain is basic emotion of fear.
Several nerve bundles, each containing numerous unmyelinated and myelinated nerves, pass into each root via the apical foramen.
majority are unmyelinated nerves, these have been shown to cause reductions in pulp blood flow when stimulated
Sensory input from peripherial receptor carried along trigeminal pathway to the cerebral cortex.
many fibers lose their myelin sheath and pass through
the cell-free zone to terminate as receptors or as free nerve endings near odontoblasts.
others pass between odontoblasts to travel a short distance up the dentinal tubules adjacent to odontoblastic processes.
The nerve endings terminate far short of the dentinoenamel junction; rather, endings are found only in tubules of the inner dentin and predentin, on or between odontoblasts.
sensory nerves of the pulp respond to noxious stimuli with pain sensation only, regardless of the stimulus. This pain is produced whether the stimulus is applied to dentin or the pulp.
cell bodies from trigeminal ganglion enter brainstem at level of pons.
These fibres synapse for the first time at main sensory nucleus of the Vth nerve.
Second order fibres arising from these sites than cross midline and ascend to synapse at thalmus.
Fibres From this thalmocortical projection pass to cortical areas concerned with dental sensation.
PAIN ASSESSMENT TOOLS Pain is a subjective experience that is communicable only through
words and behaviors.
Measuring pain intensity is extremely difficult.
Nonetheless, measuring pain is important to assess treatment outcome.
A number of instruments have been developed and tested for reliability and validity in measuring different aspects of the pain experience.
QUANTIFYING THE PAIN EXPERIENCE VISUAL ANALOG SCALES
A line that represents continuum of a particular experience, such as pain.
The most common form used for pain is a 10cm line, whether horizontal or vertical, with perpendicular stops at the ends.
Numbers should not be used along the line
No pain Worst pain imaginable
MCGILL PAIN QUESTIONNAIRE Developed at McGill University by Melzeck and Torgerson 1971
Verbal pain scale that uses a vast array of words commonly used to describe pain
These qualitative sensory descriptors are invaluable in providing key clues to possible diagnosis. Similarly, patients use different words to describe the affective component of their pain.
Melzeck and Torgerson set about categorizing many of these verbal descriptors into classes and subclasses designed to describe aspects of pain experience.
Quality of pain: categories 1 through 10 Pain intensity: category 16 Emotional or psychological overlay accompanying pain: categories 11 through 15
NUMERICAL RATING SCALES mcCaffery,M.,Beebe,A,et al.(1989) scored 0 to 10
involve asking for estimates of pain using numbers representing increasing pain severity.
require numeracy, the ability to think and express oneself in quantitative terms, and verbal communication skills.
FACES SCALES Hicks CL, von Baeyer CL, Spafford Pa, van Korlaar I ,
Goodenough B 2011;93(2):173-83
require selecting a picture of a face that represents one’s pain intensity
the task can be handled by simply matching how one feels to one of the faces
Thank you