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In this article we will discuss about:- 1. Definition of Pain 2. Types of Pain 3. Pathway for Pain and Thermal Sensations from Peripheral Parts of Body 4. Pain and Temperature Sensation from Face 5. Gate Control Theory.
Definition of Pain:
Pain is a sensory experience, which normally evokes emotional responses and is associated with autonomic and somatic motor adjustments. Pain is experienced when there is damage or potential damage to any part of body. Hence pain is a “welcome” experience for the betterment of organism.
Types of Pain:
1. Nociceptive pain:
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It is due to stimulation of nociceptors that are present in different parts of body.
2. Hyperalgesia:
Due to previous sensitization of nociceptors, painful stimulus becomes all the more painful. If innocuous thermal or tactile stimulus evokes pain, it is known as allodynia and is due to hyperalgesia.
3. Referred pain:
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Pain from deep structures, like viscera, is not felt at site of viscera but is referred to some superficial part of the body that is away. This pain is poorly localized at site of origin.
4. Neuropathic pain:
Pain occurs in absence of nociceptor stimulation. May be due to damage or irritation of peripheral nerves or in the pathway of pain in CNS. Accordingly, it may be referred to as peripheral or central pain.
a. Causalgia:
Area innervated by damaged peripheral nerve may develop severe pain and phantom limb is an example for this peripheral neuropathic pain.
b. Thalamic lesion gives rise to central neuropathic pain, which is quite severe and spontaneous.
Pain can also be classified as somatic and visceral pain. Under somatic pain, there will be superficial and deep pain.
Receptors involved:
Nociceptors are present in all parts of body except in CNS.
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There are two types of nociceptors, namely:
a. A δ mechanical nociceptors (fast pain)
b. C polymodal nociceptors (slow pain)
A δ nociceptors respond for mechanical stimuli, like pricking, crushing of skin, etc. and afferent fibers carrying impulses are A δ.
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C polymodal nociceptors respond for all types of stimuli, like mechanical, chemical or thermal and afferent fibers which carry impulses belong to C group. Differences between fast and slow pain have been enumerated in Table 9.1.
Nociceptor stimulation is responsible for initiation of inflammation around area of pain and is known as neurogenic inflammation.
Causes for hyperalgesia:
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Any type of nociceptors may undergo peripheral sensitization after exposure to strong noxious stimulus. This would be the reason for hyperalgesia. Sensitization occurs due to release of certain substances like K+, bradykinin, serotonin, histamine, etc.
Reason for hypersensitivity and other reactions at site of injury:
i. Stimulation of nociceptors
ii. Impulses generated in the nerve fiber terminal
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iii. Impulses travel along axon to CNS from concerned receptors that have got stimulated
iv. On reaching the branching area, impulses will also travel towards site of injury through other branches of nerve fiber
v. These antidromically conducted impulses bring about release of substances like:
a. Substance P
b. CGRP (calcitonin gene-related peptide)
vi. The aforesaid agents along with substances liberated by damaged cells, platelets, mast cells, etc., lead to inflammation at site of injury.
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vii. The inflammation leads to series of typical changes at site of injury, namely:
a. Tumor/swelling/(neurogenic edema)
b. Rubor/redness (due to increased blood flow)
c. Calor/warmth (due to heat production)
d. Dolor/pain (tenderness due to sensitization of pain receptors)
Referred Pain:
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Pain in viscera is not felt at site of origin but felt in some superficial part of body which is remote or far away from site of origin of pain. Reason is, concerned visceral part of body takes origin from particular segment/dermatome in embryonic life from which superficial part of body also has taken origin. Examples for referred pain are plenty.
Some of common ones are:
a. Ischemic heart pain is referred to inner part of left arm.
b. Pain in diaphragm is referred to tip of shoulder.
c. Pain in appendix is referred around umbilicus region.
Why should visceral pain get referred to superficial parts of body and not vice versa?
1. Pain always gets referred to superficial part of body of which has high density of receptors.
2. Superficial part of body gets represented quite distinctly in cerebral cortex when compared to visceral parts.
3. Till afferent fibers reach spinal cord, fibers from superficial and visceral parts are different. In neuronal axis of CNS, fibers from both superficial and visceral part synapse on common neuron and pathway continues up further like that.
4. Superficial parts of body are more prone to come across noxious stimulus when compared to visceral parts. Since in spinal cord and above, the pathway is common for both superficial and visceral pain, there will be some amount of “conditioning” that has taken place in cerebral cortex. Because of this, when pain is visceral in origin; it will be misinterpreted as if from superficial structures.
How can referred pain be explained?
Convergence theory:
Skin is most prone to get damaged rather than visceral organs. When there is stimulation of pain receptors present in skin, impulse travels along cutaneous nerve to end on a second order neuron present in posterior horn of spinal cord.
When there is stimulation of pain receptors present in viscera, impulse will go to spinal cord to end on same neuron on which somatic afferent nerve fiber has synapsed. In other words, because of convergence property of synapse, presynaptic fibers coming from different regions will be ending on common postsynaptic neuron.
Impulses coming from either visceral or cutaneous region will be able to stimulate the second order neuron to threshold value. This results in production of action potential and the impulse is carried to cerebral cortex through lateral spinothalamic tract. Sensory cortex interprets this impulse, as if coming from somatic area (skin).
Facilitation theory:
Impulses coming along nerve fibers of visceral region may not be able to stimulate second order neuron to threshold value. So second order neuron gets stimulated only to sub-threshold value.
When there is mild stimulation of pain receptors (a mild pain) in cutaneous region, sensation of pain may not be normally perceived. It is because impulses coming along afferent fibers will not be able to stimulate second order neurons to threshold value. Hence person will not experience pain sensation.
Each of sub-threshold stimuli, if occur simultaneously, effect of two sub-threshold stimuli on postsynaptic region gets added up (example for spatial summation). Because of these effects, facilitate firing of second order neuron to bring about development of an action potential.
Pathway for Pain and Thermal Sensations from Peripheral Parts of Body:
Receptors for pain and temperature are naked nerve endings which are present in almost all parts of body. The highest center for pain perception is thalamus.
The impulses reaching sensory areas of cerebral cortex help for:
1. Precise localization of painful region.
2. Differentiate whether it is pricking pain, burning pain, etc.
3. Intensity discrimination of pain
4. Emotional reactions associated with pain.
Pain impulses are carried by two different groups of nerve fibers.
a. Fast pain is by A delta fibers
b. Slow pain is by C fibers
Nerve fibers of posterior root carrying pain impulses enter spinal cord through lateral division. Fast pain fibers synapse in neurons present in lamellae I and V in dorsal/posterior horn of spinal cord.
Slow pain fibers synapse in neurons present in lamellae I and II of dorsal horn. In general, fibers carrying pain and thermal sensations synapse in substantia gelatinosa Rolandi neurons present in posterior horn of gray matter. Hence, first order neurons extend from receptor to posterior horn of spinal cord.
From substantia gelatinosa Rolandi, second order fibers take origin and they cross midline in anterior gray and white commissure in front of spinal canal. After passing through commissure, fibers reach lateral funiculus of opposite side to form lateral spinothalamic tract. Fibers of lateral spinothalamic tract will then ascend up (Fig. 9.20).
There are two types of fibers that form lateral spinothalamic tract; namely paleospinothalamic tract (spinoreticular tract) and neospinothalamic tract (spinothalamic tract). Spinothalamic/neospino- thalamic fibers synapse in ventroposterolateral nucleus of thalamus. The neospinothalamic tract fibers while passing through brainstem give collaterals to reticular formation present in this region.
The spinoreticular/paleospinothalamic tract fibers reach the reticular formation present in brainstem. In reticular formation of brainstem, these fibers have multisynaptic pathway. The fibers finally synapse in intralaminar and midline nuclei of thalamus.
From ventroposterolateral nucleus and from intralaminar and midline nuclei of thalamus, third order fibers take origin. All these fibers pass through posterior limb of internal capsule to reach cerebral cortex. Fibers coming from ventroposterolateral nucleus end in sensory cortex area no. 3, 1, and 2 only.
The fibers coming from midline and intralaminar nuclei end in sensory cortex area no. 3, 1, and 2 and also in almost all other parts of cerebral cortex.
Whenever fibers cross in spinal cord, sacral fibers come to occupy lateral most part and cervical fibers lie in medial most part. Arrangement of these fibers will be just opposite to fibers arrangement in posterior column tracts.
Pain and Temperature Sensation from Face:
From receptor, A delta fibers and C group fibers take origin. Fibers belong to 5th cranial nerve that is trigeminal nerve. Fibers carrying pain and sensation from face enter brainstem at the level of pons. In pons, these fibers pass through chief sensory nucleus but they do not synapse, instead they descend downwards into upper part of cervical segments of spinal cord.
Nucleus in which fibers end up is known as spinal nucleus of trigeminal nerve. Spinal nucleus of trigeminal nerve extends from lower part of pons to few upper segments cervical part of spinal cord. Second order neurons are constituted by fibers originating from spinal nucleus of trigeminal nerve. Fibers which have taken origin from this nucleus cross midline and ascend up though brainstem as trigeminal lemnisci.
The trigeminal lemniscus fibers synapse in ventroposteromedial nucleus present in thalamus. From this nucleus, 3rd order fibers take origin and pass through posterior limb of internal capsule and end in cerebral cortex area no. 3, 1, and 2 (sensory area of cortex) in lateral most part where face is represented (Fig. 9.21). Right half of face is represented in left cerebral hemisphere and vice versa.
Gate Control Theory of Pain:
C group fiber entering spinal cord (slow pain) release substance P, which in turn stimulates substantia gelatinosa (SG) neurons (the gate) in spinal cord. Impulses from SG in turn stimulate ‘P’ cells. From ‘P’ cell, spinoreticular tract fibers take origin. Spinoreticular tract fibers carry slow pain sensation (Fig. 9.22).
When A δ fibers (fast pain) are stimulated, collateral from A stimulates ‘I’ cells in spinal cord. This neuron (‘I’ cell) later on inhibits SG and hence gate for slow pain gets closed. A δ fibers bring about stimulation of ‘M’ cells in spinal cord. From ‘M’ cells, fibers that are going to contribute for formation of neospinothalamic or spinothalamic tract take origin. This tract is concerned with conduction of fast pain impulses.
When there is massaging, and application of pain balms (leads to counter irritation), transcutaneous electrical nerve stimulation (TENS), acupuncture etc., A β fibers (which carry other sensations, like touch, pressure) get stimulated.
They presynaptically inhibit (for details refer to presynaptic inhibition) fibers of C group ending on SG and does not allow opening of gate. Hence no impulse production in SG neurons. So person gets relief from pain.
Impulses coming along dorsolateral funiculus (DLF) release serotonin (5 HT). This neurotransmitter stimulates ‘I’ cells. ‘I’ cells now postsynaptically inhibit SG by releasing enkephalin (ENK). This leads to closing of gate and hence there will be no action potential production from SG cells.
Descending Analgesic System or Endogenous Analgesic System (EAS):
Neurons in periventricular gray (PVG) and periaqueductal gray (PAG) in midbrain (Fig. 9.23) have excitatory influence on nucleus raphe magnus (NRM) present in medulla oblongata.
The neurons of PVG and PAG are stimulated by impulses coming from cerebral cortex. This will be responsible for stress-induced analgesia in any life- threatening situation. PAG and PVG also get stimulated by ascending fibers (lateral spinothalamic fibers) which are carrying pain and thermal sensations.
Descending fibers pathway that take origin from NRM are termed as dorsolateral funiculus (DLF), and they end on I cells present in dorsal horn of spinal cord. DLF fibers stimulate ‘I’ cells by releasing 5 HT and these ‘I’ cells subsequently inhibit SG (close the gate) by releasing enkephalin.
One of the groups of neurotransmitters liberated by EAS is termed as opioid peptides that include enkephalin, endorphin and dynorphin. Administering substances, like morphine, can augment activity of EAS. DLF fibers can also release neurotransmitters which are non-opioid in nature.
Administering naloxone can inhibit opioid substance mediated analgesic activity.
Stress can stimulate both opioid and non-opioid analgesic fibers as occurs during any emergency. This occurs in soldiers injured in battleground, athletes injured in sports events, etc.
Pain Relieving Surgical Procedures:
When people suffer from intractable pain in certain cancerous conditions and when medical management is almost not helping, surgical methods may have to be resorted to. In such a situation, interruptions in pathway of pain may be of choice. In many of these procedures, either person does feel pain, or will not react to pain.
Interruption in pathway can be outside spinal cord, in spinal cord or even in higher parts of central nervous system. The pathway can be sectioned either outside spinal cord or in spinal cord more easily when compared to sectioning pathway in higher parts of CNS like in thalamus or cerebral cortex.
Some of the surgical procedures that can be employed when there necessity for interruptions in pathway is:
1. Peripheral nerve sectioning:
Especially when somatic nerves sectioning is a must. One of the problems with this sectioning is, since there is complete sectioning of peripheral nerve, in affected part of body, there can be complete loss of sensations.
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2. Sympathetectomy:
From viscera, pain sensation from most of structures is carried by sympathetic afferent fibers. So relief from pain which is getting originated from viscera can be achieved by performing sympathectomy.
3. Posterior rhizotomy afferent nerves before they enter spinal cord, get separated into two bundles, namely lateral and medial divisions. Fibers of medial division will contribute for formation of posterior column tracts which carry fine touch, proprioception, etc.
Fibers of lateral division contribute for formation of spinothalamic tracts. Hence by cutting lateral division alone, selective loss of pain, temperature and crude touch can be established in desired parts of body.
4. Myelotomy:
In this procedure, fibers crossing midline in anterior gray and white commissure which are going to contribute for formation of lateral spinothalamic tract are cut off. This procedure is helpful especially when there is need to relieve pain on either side of body at particular regions.
5. Anterolateral cordotomy:
In this procedure, there will be sectioning of lateral spinothalamic tract on any one side. Since lateral spinothalamic tract is present in lateral funiculus, selective lesion of this tract can be performed.
6. Prefrontal lobotomy:
Here white matter connection of prefrontal lobe with other parts of cerebral cortex is cut off. Following this procedure, person can still feel pain, since thalamus is highest center for pain perception and impulses are reaching thalamus. But person’s reaction to pain will be absent.
Pathway for Crude Touch from Peripheral Parts of Body:
Crude touch sensation from peripheral parts of body is carried by anterior spinothalamic tract. Receptors involved are free nerve endings and nerve fibers which carry these impulses are A beta.
From receptor A beta fibers which carry impulses enter spinal cord through lateral division of dorsal nerve root. These fibers synapse in nucleus proprious. From nucleus proprious, 2nd order fibers take origin, cross the midline in anterior gray and white commissure in front of central canal.
These fibers after crossing reach white matter in anterior funiculus and ascend up as anterior/ventral spinothalamic tract. While passing through brainstem, anterior spinothalamic fibers give collaterals to reticular formation.
Fibers finally reach ventroposterolateral nucleus of thalamus and synapse. From this nucleus the 3rd order fibers take origin, pass through posterior limb of internal capsule to end in cerebral cortex area no. 3, 1, and 2 in postcentral gyrus.
