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Pain and pain pathway

Introduction

           The medicine must preserve and revive vitality and alleviate distress. Knowing pain pathway is primary to both these purposes. Because pain is universally understood as a flag of disease, it is the most common symptom that brings a patient to a doctor’s attention. The purpose of the sensory pain system is to identify, restrict, and recognize damaging tissue manners.

           As various conditions present specific patterns of tissue destruction, the quality, time sequence, and location of a patient’s pain complaint and the location of tenderness provide important diagnostic clues and are used to evaluate the response to treatment. 

           Unlike other sensations, however, pain is an experience that cannot be shared; it is wholly personal, belonging to the sufferer alone. 

Importance of Pain

           Pain is a shielding mechanism for the body; it happens whenever any tissues are being destroyed, and it causes an individual to react to the stimulus. 

           It is an unpleasant sensation, no doubt, but on the whole, it is usually beneficial to man (animal). It makes us conscious of the presence of injurious agent, and that is why we seek the removal of injurious agents by appropriate means. 

           But in some cases, pain may be counterproductive to the interest of the patient e.g. pain in incurable cancers where presence of pain only adds to the misery of the patient. 

Definition of Pain

           In this era, the idea of pain has developed from that of one-dimensional response to that of a multidimensional experience encompassing sensory, discriminative, cognitive, motivational and affective qualities. 

           The most recent definition of pain, produced by Task Force on Taxonomy of the International Association for the study of pain is, “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such a damage”. 

There is an accompanying explanatory note:-

• Pain is not a pure sense as is hearing, vision and the like and cannot be dealt with as such. Rather pain is an emotional experience as attested to by the complex interactions involving the action system. Fear, anxiety, past experience and suffering are all components of the unpleasant episode. 
• The experience is usually created by a noxious stimuli, but this is not always the case. In some pain syndromes, no stimulus can be found, and in other instances, only stimuli that is generally felt to be non-noxious may be identified. 

Monheims’ definition of pain: “Unpleasant emotional experience usually initiated by a noxious stimulus and transmitted over a specialized neural network to the CNS where it is interpreted as such”. 

Measurement of Pain

           There is no single way of measuring pain. The severity of a particular pain is based on what is verbally or non-verbally communicate about the experience. 

           Patients often express difficulty in describing pain, and two people may have very different descriptions for pain that accompanies a similar injury.

           In assessing pain, its intensity, emotional distress, and associated disability are important and cannot be captured with one scale or questionnaire. 

           Pain severity can be estimated by using grades such as Visual Analog Scale (VAS).

           A VAS consists of a 10 cm line on which 0 cm is “no pain” and 10 cm is “pain as bad as it could be”. The patient indicates the point along the line that properly portrays his/her pain, and the score is ranked from “No pain” end of the scale. 

Pain Receptors and Transmitters

Pain receptors – Are called nociceptors or free nerve endings 

           Pain receptors are observed in nearly every tissue of the body. They may react to any kind of provocation if it is strong enough to create tissue damage. When stimuli for other feelings such as touch, pressure, heat and cold reach a certain intensity, they stimulate the sensation of pain as well. 

           Other stimuli that elicit pain include excessive distension or dilation of a structure, prolonged muscular contraction, muscle spasm, inadequate blood flow to an organ or presence of certain chemical substance.

           Pain receptors, because of their responsiveness to all incentives, make a protective role by recognizing differences that may jeopardize the body. 

Chemical Mediators / Transmitters of Pain:

           A number of biochemical factors are also associated with transmission of pain, some act as allogenic substance, some as neurotransmitters and some in both capacities. 

i) Bradykinin:- Endogenous polypeptide released from the inflammatory reaction or from ischemic tissues serves as a vasodilator in addition to increasing vascular permeability. 

           Also excites all types of receptors, sensitizing some high threshold receptors to respond to otherwise innocuous stimuli. 

           Acts only in the presence of prostaglandins. 

ii) Histamine:- Vasoactive amine 

           Action à Vasodilation + increased small vessel permeability 

           Also functions as a CNS neurotransmitter 

           Released from mast cells and basophils 

iii) Prostaglandins:- These sensitize nociceptors to different types of stimuli thus lowering their pain threshold to all types of stimulation. 

           Required for action of bradykinin. 

iv) Serotonin:- Peripherally, it is associated with vascular pain, as an allogenic agent. 

           Centrally, this monoamine appears to be an important endogenous antinociceptive mechanism. 

v) Substance P:- This polypeptide acts centrally as an excitatory neurotransmitter for nociceptive impulses. It is also released from spinal cord by Ad & C fibre afferent stimulation and excites dorsal horn neurons that are activated by noxious stimuli.

           Its action is both rapid and short lived.

vi) Other agents:- Ach; K; and variety of endogenous toxic substances serve as algogenic substances. 

Endogenous Pain Inhibiting Mechanism:

           Intensity of injury may remain same but different person/ or the same person at different times may feel the pain differently. Even a nasty injury thus at a particular setting, may cause no pain at all. 

           This is because our body has endogenous pain inhibiting system. If this system is over reactive, pain perception may be abolished altogether. 

           The endogenous pain inhibiting system has 2 subgroups. 

a) Descending pain inhibiting system 

b) Gate control mechanism 

a) Descending Pain Inhibiting System (DPI): 

           PAG (periaqueductal gray) is an area around the Aqueduct of Sylvius in the midbrain. From PAG a bunch of fibres descending arise à Relay in Magnus Raphe nucleus à Next order neuron terminate at SGR. This is DPI.

           1st order neuron which carry pain from periphery terminates at SGR – from here 2nd order neuron emerges and form STT which terminates in thalamus. Here the neurotransmitter is substance P.

           When DPI is stimulated, the terminal part of DPI releases some endogenous opioid peptides as Neurotransmitters at SGR, these endogenous opioids peptides causes inhibition of substance P. Transmission block of pain sensation results – No pain felt. 

b) Gate Control:

           When a painful stimulus alone is applied, the pain is more intensely felt than where the same intensity is applied concomitantly with a tactile stimulus.

           This occurs because the gate control proposed theory by Melzack and Wall in 1965. 

Details:- Let a painful (nociceptive) stimulus be applied in the periphery. Pain is carried by primary afferent, which terminates in SGR. From here 2nd order neuron forms STT. 

           Also, tract of Goll & Burdach (Lemniscal fibres) carrying tactile senses pass through the dorsal column remaining close to SGR. On its way it gives collaterals to the termination of primary pain carrying afferent at SGR. Via these collaterals it effects a presynaptic inhibition on the primary pain carrying afferent. Pain sensation is inhibited. 

Types of Pain

i) Fast pain/ Slow pain:

           Immediately after an injury (i.e. stimulus) a sharp localized pain is felt; which is called fast pain and is carried by A delta fibres at a higher speed. A delta fibres are somewhat thick and finely myelinated fibers from 3-20 m in diameter conduct fast / first pain at the rate of up to 100m/sec.

           After fast pain a diffuse, dull, intense and unpleasant pain sensation occurs which is called slow pain and is carried by C fibres which are small unmyelinated nerve fibres 0.05 – 1m in diameter and conduct the slow or second pain at a rate of 0.5 – 2m/sec. 

ii) Epicratic / Protopathic Pain:

– Epicratic pain is low threshold but has accurate localization. 

– Protopathic pain – High threshold but poor localization 

iii) Deep/ Superficial pain: 

– Pain from deeper structures like periosteum, muscle, tendon is called deep pain and is poorly localized.

– Superficial pain arises from superficial structures like skin and can be easily localized. 

iv) Somatic / Visceral Pain: 

– Somatic pain arises from somatic structure e.g. skin and may be superficial or deep. 

– Visceral pain originates from viscus due to inflammation, spasm, stretching etc. It is poorly localized and is diffuse. 

v) Referred and Radiating Pain: 

           Visceral pain instead of being felt at the site of the viscera is frequently felt at some distance, on somatic structure – such as pain is called referred pain. E.g. Cardiac pain is felt at the left arm and left lower jaw. This means the visceral pain is referred to the dermatome which has developed from the same segment (somite) as the viscus. 

           When the visceral pain is felt both at the site of the viscus and also at the referred site, then it is called radiating pain. 

Theories of Referred Pain

i)             Facilitation Theory:- According to this theory, the visceral pain produces a subliminal fringe effect i.e. lower the threshold of spinothalamic neurons, on the SGR (substantia gelatinosa) which receive somatic pain. These SGR are then easily stimulated by minor stimuli on the skin and hence the pain is now felt on the skin. 

ii)            Convergence Theory:- Fibres carrying pain, both from the viscus and the corresponding dermatome, converge to the same pain pathway to the cortex. Now this pain pathway if stimulated by any means e.g. due to inflammation of the viscera, the pain felt is projected to the site of the receptors on the skin. This is because the brain has learned to do so as somatic pain is more common. 

iii)           Role of Experience:- Experience since childhood. It is seen that an injury on the skin produces pain, so one learns to co-relate pain with injury on skin (experience). On the other hand a subject has no idea of the viscus, its situation etc. so when pain originates from the viscus by experience one tries to feel it or project it to the dermatome instead of viscus. 

Various terms used to describe pain:-

• Intermittent: Pain of short duration separated by wholly pain free periods. 
• Continuous: Pain of long duration, even though variable in intensity. 
• Recurrent: Two or more similar painful episodes. 
• Remission: Two or more similar painful episodes with intermittent pain free intervals.  
• Periodic pain: Regular recurring episodes. 

Characteristics (Properties) of Pain

1.    Threshold and intensity:- If the intensity of the stimulus is below the threshold (subthreshold), pain is not felt. As the intensity increases more and more pain is felt more and more pain sensation spreads i.e. it begins to be felt in the neighboring regions also. However, if the mind is distracted threshold of pain increases, severe excitement and emotion can altogether abolish even a severe pain. 

2.    Adaptation:- Pain receptors show no adaptations and so pain continues as long as the receptors continue to be stimulated. 

3.    Localisation of pain:- Pain sensation is somewhat localized.

4.    Emotional accompaniment:- Pain sensations are commonly accompanied by emotions. These emotions as a rule are unpleasant. 

5.    Influence of the rate of damage on the intensity of pain:- If the rate of tissue damage or injury is high intensity of pain is also high and vice versa. 

6.    Weber Fechner’s law:- Magnitude of sensation felt is proportionate to the log of intensity of the stimulus. E.g. arbitrarily if stimulus is ten sense perceived is one stimulus is 100 sense perceived is 2. It means if stimulus is increased ten times sense perceived will be just doubled 

Reactions of Pain

i) Behavioral:- Crying/ moaning 

ii) Muscular or motor effects

           Spasm of the skeletal muscles in the affected region develops e.g. Masseter muscle spasm in TMJ dysfunction pain. This spasm may be beneficial as it causes immobilization of the injured part and puts the affected part to forcible rest. However muscle spasm may cause ischemia of the muscle and further aggravation of muscle pain. 

iii) Changes in autonomic nervous system: 

           Somatic pain is usually accompanied by signs of sympathetic overactivity, e.g. rise of BP, tachycardia, and papillary dilatation e.g. facial flushing with a dental abscess. 

iv) Reflex response:

           Reflex motor response to pain is known as withdrawal reflex. A painful stimulus is usually associated with a somatic reflex. These reflexes remove a part of the body from the noxious stimulation e.g. when a hard object is encountered in mastication or functional tooth contacts cause pain. The jaw reflexly opens. This protective mechanism does not function during sleep. This is one of the numerous reasons for removing dentures during sleeping hours to prevent damaging force to the tissues. 

Dual Nature of Pain:

Pain perception and pain reaction

Pain Perception: Is the physioanatomical process whereby an impulse is generated following application of an adequate stimulus and is transmitted to the CNS. This aspect of pain is remarkably similar in all healthy individuals and varies little from day to day. Stimulus intensity, as well as the duration for which it must be applied, are relatively uniform, as is the rate of impulse conduction for particular nerve type. 

Pain Reaction: Psychophysiological process that represents the individual overt manifestation of the unpleasant perceptual process that just occurred. The complex factors determine how the individual will react to the unpleasant experience. Unlike pain perception, pain reaction varies markedly from one individual to another and from day to day in the same individual. 

           A patient who is hyporeactive is considered to have high pain threshold and a patient who has a low threshold hyper reacts in response to noxious stimuli. 

           If pain is to be controlled both aspects of its nature must be considered. 

Factors affecting pain reaction:

i) Emotional status: Emotionally unstable patients have a low pain threshold so increased pain reaction. 

ii) Fatigue:- It has been shown that patients who are well-rested and who have had a good night sleep previous to an unpleasant experience will have a much higher pain reaction threshold than an individual who is tired. 

iii) Age: Older individual tend to tolerate pain and thus have higher pain reaction threshold than younger individual / children. But in cases of extreme age/ senility, pain perception itself may be affected. 

iv) Sex: Men have higher pain threshold than women. This may be a reflection of man’s desire to maintain his feeling of superiority which is exhibited in his predetermined effort to tolerate pain. 

v) Fear and apprehension:- Increase of fear and apprehension reduces pain threshold. These patients tend to magnify the pain out of all proportion to the original stimulus, and they are hyper-reactive. 

Pain pathway

           The anterolateral system or spinothalamic tract (STT) carries pain, crude touch and temperature sense. There are two tracts in this pain pathway system viz. anterior (ventral/ ant STT) and lateral STT and hence the name anterolateral system. 

The anterior STT – Carries crude touch senses 

The Lateral STT – carries pain and temperature 

           The senses of pain are brought to the spinal cord by 1st order neuron. In particular, the pain pathway fibres are carried by C (slow pain) and Ad (fast) group of fibres. 

           The 1st order neuron enter (via the dorsal root ganglion (DRG) the cord and terminates in the dorsal horn by synapse with the next order neuron. In particular, the 1st order neuron of pain pathway fibre terminates at SGR. 

           The 2nd order neurons, which constitute the STT –fibres cross the midline in front of the central canal to form STT. 

           The STT enters the medulla and proceeds upward. These fibres terminate in the thalamus, particularly in the ventral posterolateral nuclei of the thalamus. 

           On its way to the thalamus the anterolateral system or STT gives off/ channels which terminate chiefly on the reticular activating system of fibres. This follow that when the STT is stimulated (as in pain) the mind becomes alert and sleep disappears. 

           Pain pathway is also relayed to the components of the limbic system which are responsible for the emotional response caused by pain sensation. 

Theories of Pain Transmission Through Dentin

           The sensitivity of dentin has long been recognized as a clinical entity, however, the exact mechanism for initiation and transmission of painful impulses from this seemingly insert structure has remained a mystery until recently. 

The various theories of dentinal hypersensitivity are:-

a)    Direct Neural Stimulation:- Dentinal sensitivity is a result of direct stimulation of sensory nerve endings in the dentin, stimuli in some manner yet unknown reach the nerve endings in the inner dentin. However clinical studies have shown that the sensitive area of the tissues is near the DEJ the area farthest from the nerve. There is little scientific support for this theory. 

b)   Transduction Theory:- This theory presumes that odontoblast is sensory cells. Through their processes in the dentinal tubules, odontoblast receives and transfers stimuli to nerve endings in the pulp. This theory had substantial support until recently SEM studies failed to show the presence of odontoblastic processes in the peripheral dentin. 

c)    Hydrodynamic Theory:- Various stimuli such as heat, cold, air blast dessication, or mechanical pressure affect fluid movement in the dentinal tubules. This fluid movement either inward/ outward stimulates the pain pathway mechanism in the tubules by mechanical disturbance of the nerve closely associated with the odontoblast and its process. This ending may act as mechanoreceptors as they are affected by mechanical displacement of tubular fluid. This critical factor in the degree of pain noted is the rate of change of fluid flow and not the maximum flow rate produced. 

Methods of Pain Control

           Any method of pain control will affect either pain perception or pain reaction or both. 

Following are the methods of pain control:- 

1. Removing the cause 
2. Blocking the pathway of painful impulses 
3. Raising the pain threshold – Pain reaction + Perception 
4. Preventing pain reaction by cortical depression – affects pain reaction 
5. Using psychosomatic methods 

1. Removing the cause

Most desirable method of controlling pain 

           If this could be achieved, the environmental change in tissue would be eliminated consequently free nerve endings would not be excited and no impulses would be initiated. It is imperative that any removal leave no permanent environmental changes in tissues since this condition would then be able to create the impulse, even though the original causative factors had been eliminated. Affects pain perception. 

2. Blocking the pathway of painful impulses

           This is the most widely used method of pain pathway in dentistry for controlling pain. By this method a suitable drug possessing local analgesic properties, is injected into the tissues in proximity to nerve or nerves involved. The LA solution prevents depolarization of the nerve fibres at the area of absorption, thus preventing these particular fibres from conducting any impulses centrally beyond that point. As long as the solution is present in the nerve in sufficient concentration to prevent depolarization, the block will be effective. Affects pain perception 

3. Raising the pain threshold

           In recent years the dentist has become more aware of and has shown a greater appreciation for this method of pain control. Raising the pain threshold depends upon pharmacological action of drugs possessing analgesic properties. In this method the cause of the original status may still be present. 

           The neuroanatomical pain pathway is intact and able to conduct impulses. In other words pain perception is unaffected, but pain reaction is decreased thus the pain reaction threshold is raised. 

           It should be clearly understood that the pain threshold can be raised to limited degrees only, depending on the specific drug used. It is physiologically impossible to eliminate all pain of the most severe nature by raising the pain threshold alone. 

           Various drugs possess analgesic properties in varying degrees and thus some are more effective in raising the pain threshold than others. Certain drugs like aspirin are effectively only in the relief of mild discomfort, narcotics are effective against more severe pain because they raise pain threshold to a greater degree. 

4. Preventing pain reaction by cortical depression

           This is within the scope of GA and its agents. It increases depression of the CNS, thus prevents any conscious reaction to a painful stimulus. In those cases where the central cortex is depressed only to the point that the inhibitions are suppressed, the patient may become hyperreactive to a painful stimulus. Therefore any stimulus should be avoided in these instances. 

5. Using psychosomatic methods

           This is one of the methods in which so much can be gained with so little ill effect on the patient. It affects both pain perception and reaction and depend for its effectiveness on putting the patient in the proper frame of mind. It is amazing what can be accomplished without the use of drugs when the patient’s faith and confidence are gained; for this doctor should be honest and sincere towards the patient; and the patient is informed about the procedure and what might be expected. 

           Patients like to believe that their comfort is of prime consideration to the dentist. Once they are secure in this feeling they will tolerate unpleasant sensation to a greater degree. In this manner pain reaction reduces and pain threshold increases. 

Psychogenic Pain:

           Psychogenic pain may be defined as that unpleasant sensation that has no organic basis. It is any pain that originates wholly within the mind and is fixed on some portion of the anatomy. 

           The dentist should be careful about establishing the diagnosis of psychogenic pain. All methods and means of locating a possible organic source of pain should be exhausted before the psychogenic cause is contemplated. 

           No drastic steps should be taken to alleviate the patient’s pain if there is any possible that it may be psychogenic. 

Causes of Orofacial Pain

• Neuralgia: Trigeminal neuralgia, Glossopharyngeal neuralgia 
• Vascular: Migraine, cluster headache 
• Muscular: MPDS, TMD
• Idiopathic: Atypical facial pain, Phatom tooth pain 

During the examination and history the various characteristics of pain to be noted are:-

– Intensity 

– Quality 

– Location

– Onset

– Associated events on onset

– Cause of symptom since onset

– Activities with increase or decreased pain 

– Associated symptoms (e.g. swelling, nausea) 

– Previous treatment and their effect 

Pain originating from different sources have varying characteristics:-

1. Neurogenic pain: Sharp, burning, and intensed. May be constant or intermittent 
2. Vascular pain: Diffuse, may be referred thus difficult to localize 
3. Muscle pain: Most likely dull. Limited to the area of origin. Movement of the part intensifies the discomfort. 

Various Terms:

• Allodynia: Pain due to a generally non-noxious stimuli 
• Analgesia: Lack of pain on noxious stimulation 
• Anesthetic Dolorosa: Pain in an area or region that is anaesthetized 
• Hyperalgesia: Increased sensitivity to noxious stimulation, reduced pain threshold. 
• Hypoalgesia: Decreased sensitivity to noxious stimulation 
• Neuralgia: Pain in the distribution of a nerve 
• Noxious stimulus: Tissue damaging stimulus 
• Pain threshold: Least stimulus intensity with a subject perceives pain 

Analgesics:

           Definition: A drug that selectively relieves pain by acting in the CNS or on peripheral pain pathway mechanisms, without significantly altering consciousness. 

           They are used when the noxious stimuli cannot be removed or as adjuvants to more etiological approach to pain:

A) Opoid/ narcotic/ morphine like analgesics

B) Non-opoid/ non-narcotic/ aspirin like/ antipyretic or anti-inflammatory analgesics

Opoid Analgesic-like Morphine:

Action: It is strong analgesic, though dull, poorly localized visceral pain is relieved better than sharply defined somatic pain. 

           Pain perception and reaction to it both are altered so that it is no longer as unpleasant or distressing i.e. patient tolerates pain better. It inhibits the release of substance P (chemical mediator of pain) and even affects the limbic system. 

           They are used for tooth ache or dentistry when aspirin like analgesics are not effective; either alone or in combination with aspirin like drug. The combination is supradditive. 

NSAIDs:

           They act primarily on peripheral pain pathway mechanism, also in CNS, to raise pain threshold. 

           Aspirin is a weaker analgesic than morphine type drugs. It inhibits prostaglandin synthesis and blocks this sensitization of pain pathway mechanism. It relieves inflammatory, tissue related injury, connective tissue and integumental pain but is relatively ineffective in several visceral and ischaemic pain. 

           It does not have cortical action on psychic processing or on the reaction component of pain or pain pathway.

           Dosage for toothache: 0.3 – 0.6 g TDS 

Conclusion

           Pain is a multidimensional experience involving both the sensation evoked by a noxious stimulus but also the reaction to it. The sensation of pain, therefore, depends in part on the patient’s past experience, personality and level of anxiety. So before any attempt is made to control or eliminate pain by any method, the patient should receive the benefit of a diagnosis as careful as possible.

           No treatment should be prescribed on a “per-chance” basis, since pain is a symptom and should not be treated without a plan. Every effort should be made to locate the source of pain and to treat the pathologic condition rather than the discomfort alone.