Handbook of Pain Management in Practice Sree Ranjani S
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Basics of PainChapter 1

The word pain comes from the Latin word ‘poena’, which means ‘punishment’. From times immemorial, pain was considered as a form of punishment meted out by God for the sins committed by man. The word pain brings to one's mind misery and suffering. The French physician, Albert Schweitzer, proclaimed in 1931 that, “pain is a more terrible lord of mankind than even death itself.”
The International Association for the Study of Pain (IASP) has published the following definition of pain. Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”1
The term ‘nociception’ refers to the process by which pain information is carried from the peripheral sense receptors in the skin and in the viscera to the cerebral cortex through network of neuronal relays. There are four basic processes involved in nociception.2 These are:
  1. Transduction.
  2. Transmission.
  3. Perception.
  4. Modulation.2
Transduction of Pain
Transduction (Fig. 1.1) begins when the free nerve endings (nociceptors) of C fibers and A-delta fibers of primary afferent neurons respond to noxious stimuli.
  1. The A-delta fibers are primary afferent fibers, large diameter, myelinated and fast conducting. The quality of pain produced by them is a well-localized, sharp, stinging or pricking and referred to as ‘fast’ or ‘first’ pain.
  2. The C fibers are primary afferent fibers of small diameter, unmyelinated and slow conducting. The pain quality produced by them is diffuse, dull, burning or aching and referred to as ‘slow’ or ‘second’ pain.
Nociceptors are the free nerve endings, which respond to pain. The nociceptors are distributed in the:
  1. Somatic structures: Skin, muscles, connective tissue, bones and joints.
  2. Visceral structures: Visceral organs such as liver, gastro-intestinal tract (GIT).
Noxious Stimuli
In noxious stimuli there are three types:
  1. Thermal (burns/scalds).
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    FIGURE 1.1: Transduction of pain
  2. Chemical (toxins/ischemic changes/infection).
  3. Mechanical (pressure/swelling/incision).
This noxious stimulation causes a release of chemical mediators such as prostaglandin, bradykinin, serotonin, substance P, potassium and histamine from the damaged cells. These chemical mediators activate and/or sensitize the nociceptors to the noxious stimuli. This results in generation of a pain impulse.
Transmission of Pain
The pain impulse is transmitted from the site of transduction along the nociceptive fibers to the substantia gelatinosa in the dorsal horn in the spinal cord. The C fiber and A-delta fibers terminate in the dorsal horn of the spinal cord and cause a release of excitatory neurotransmitters such as adenosine triphosphate (ATP), glutamate, calcitonin gene-related peptide, bradykinin, nitrous oxide and substance P. The pain impulse now reaches the nociceptive dorsal horn neurons (Fig. 1.2).
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FIGURE 1.2: Transmission of pain
The pain impulse is then transmitted from the spinal cord to the brainstem and thalamus via two main nociceptive 4ascending pathways namely spinothalamic pathway and the spinoreticular pathway. Other pathways involved in the transmission are spinoparabrachial pathway, dorsal column pathway, spinomesencephalic tract and spinohypothalamic pathway.3 From the thalamus, the impulses are directed to multiple areas in the brain, where they are processed, as the brain does not have a discrete pain center.
Perception of Pain
Perception of pain is the end result of the neuronal activity of pain transmission and where pain becomes a conscious multidimensional experience. The multidimensional experience of pain has affective-motivational, sensory-discriminative, emotional and behavioral components.4 When the painful stimuli are transmitted to the brainstem and thalamus, multiple cortical areas are activated and responses are elicited (Fig. 1.3).
Reticular System
Reticular system is responsible for the autonomic and motor responses to pain, for example, automatic withdrawal of a hand when it touches a hot object. It also has a role in the affective-motivational response to pain such as looking at and assessing the injury to the hand once it has been removed from the hot object.
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FIGURE 1.3: Perception of pain
Somatosensory Cortex
Somatosensory cortex is involved with the perception and interpretation of sensations. It identifies the intensity, type and location of the pain sensation and relates the sensation to past experiences.
Limbic System
Limbic system is responsible for the emotional and behavioral responses to pain. For example, attention, mood and motivation along with processing pain and past experiences of pain.
Pain is so important to survival that almost the whole brain is involved and no discrete center for pain is recognized. Position emission tomography (PET) scan data obtained during painful stimulation indicated activity in sensory and motor cortex areas, premotor cortex, parts of the parietal cortex, parts of the frontal cortex, cingulate cortex, insula, occipital cortex, subcortical structures such as thalamus, putamen, caudate nucleus, hypothalamus, amygdala, periaqueductal gray matter, hippocampus, red nucleus, pulvinar and vermis of the cerebellum.5 This supports Dennis Turk's claim that ‘the reign of pain is mainly in the brain’. But there is no one center ‘in control’.
Modulation of Pain
When the pain impulse reaches the brain, multiple cortical areas are stimulated including certain complex pathways called descending modulatory pain pathways (DMPP) present in periaqueductal gray, the lateral reticular formation, raphe nuclei, the locus coeruleus and various regions of the medullary reticular formation as well as sites in the hypothalamus, septum, orbital cortex and sensorimotor cortex.6 These release pain modulators, the inhibitory neurotransmitters that block or partially block the transmission of pain impulses (Fig. 1.4).
Hence, the final perception of pain and/or analgesia is subject to the modulatory activities of these endogenous pain modulators such as gamma-aminobutyric acid (GABA), endogenous opioids (enkephalins and endorphins), serotonin [5-hydroxytryptamine (5-HT)], norepinephrine (noradrenaline), neurotensin, acetylcholine and oxytocin, which are inhibitory neurotransmitters and found throughout the central nervous system (CNS). There are wide variations in the perception of pain in different people. This is because of the varied production of these endogenous pain modulators (Fig. 1.5).6
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FIGURE 1.4: Pain modulation
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FIGURE 1.5: Pain pathway
In 1994, responding to the need for a more useful system for describing chronic pain, the IASP classified pain according to specific characteristics such as region of the body involved, system whose dysfunction may be causing the pain, duration and pattern of occurrence, intensity and time since onset and etiology.7
This system was considered inadequate by Woolf8 and an additional category based on neurochemical mechanism was proposed by Turk, et al.9 Classification of pain is thus complicated and can be a source of confusion for many clinicians.10 7
Depending on Major Site of Origin
  1. Peripheral pain: Originates in muscles, tendons, etc. or in the peripheral nerves themselves.
  2. Central pain: The IASP defines central pain as “pain initiated or caused by a primary lesion or dysfunction in the central nervous system.”11 Central pain is the most difficult type of chronic pain to manage. It results from injury to the ascending pain pathways and associated structures, and may be seen in a wide range of conditions including stroke, multiple sclerosis, and Parkinson's disease.
Physiological Classification
Nociceptive Pain
In this pain, normal nerves transmit information to the CNS about trauma to tissues. Nociceptive (nocere—injure, Latin) pain is detected by specialized transducers attached to A-delta fibers and C fibers. Nociceptive pain is divided into somatic and visceral (Fig. 1.6).
  1. Somatic pain results from irritation or damage to the musculoskeletal system. It is further divided in to superficial and deep pain.
  2. Visceral pain is diffuse, poorly localized, and often referred.
Neuropathic Pain
Neuropathic pain is pain in which there are structural and/or functional nervous system adaptations secondary to injury that take place either centrally or peripherally.12 This pain can result from trauma, infection, ischemia, cancer or chemically induced, even by chemotherapy.13
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FIGURE 1.6: Classification of nociceptive pain
It is distinctly different from 8nociceptive pain and is described as burning, dull aching, tingling, e.g. electric shock or shooting. Differentiate neuropathic from neurogenic pain, which is term used to describe the pain resulting from injury to a peripheral nerve. “Every nerve that can thrill with pleasure can also agonize with pain” (Horace Mann).
Based on Occurrence
  1. Continuous pain: Lasts all through the day.
  2. Intermittent pain or recurrent pain: Occurs on and off. Episodes of pain interspersed with periods of being completely pain free.
  3. Breakthrough pain: Pain that comes on suddenly for short periods of time and is not alleviated by the patient's normal pain medication. It is common in cancer patients who have a background level of pain controlled by medications, but the pain periodically ‘breaks through’ the medication.
  4. Incident pain: Pain that arises as a result of activity such as movement of an arthritic joint, stretching a wound, etc.
  5. Transient pain: It is very common in everyday life. This type of pain ceases as soon as the stimulus is removed (e.g. venipuncture).
Based on Nature of Pain
The main types of pain described by this system of classification are:
  1. Gnawing pain: Continuous with constant intensity, it generally worsens with movement.
  2. Throbbing pain: This is typical of migraine pain, it pulsates.
  3. Stabbing pain: It is intense and severe. It is caused by mechanical stimuli.
  4. Burning pain: A constant, burning feeling, e.g. the type of pain caused by heartburn.
  5. Pressing pain: Caused by constriction of the blood vessels or muscles.
Based on Intensity
The intensity of pain is uniquely subjective, because intensity varies for most patients over time. One patient might rate the experience of pain resulting from some pathological condition as a 10 (Fig. 1.7), whereas another patient with the same pathology might describe the intensity of pain only as a 5, both using a 0–10 scale (with 0 signifying no pain at all and 10 representing the worst pain imaginable).9
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FIGURE 1.7: Pain rating scale
Based on Anatomical Site of Origin
Examples for pain types based on anatomical site of origin are headache, neck ache, backache, abdominal pain, etc.
Temporal Classification
Temporal classification of pain is the commonest classification. Described in terms of acute and chronic pain are detailed in Table 1.1.
Table 1.1   Temporal classification of pain
Acute pain
Chronic pain
Lasts for a short duration
Lasts for a long time
Has identifiable pathology
Has unclear pathology
Has a predictable prognosis
Has unpredictable prognosis
Occurs in presence of ongoing illness and lasts till healing occurs
Occurs in the absence of ongoing illness or after healing is completed
Treatment usually includes analgesics
Treatment should be multidisciplinary
Travels along the neospinothalamic tract
Travels along a slower tract, called the paleospinothalamic tract14
Terminates in the thalamus and the cortex
Terminates in the limbic structures and the hypothalamus (responsible for stimulating the release of stress hormones)
This pain is protective
This pain usually does not serve any useful function
Chronic Pain
Chronic pain can be caused by alterations in nociception, injury or disease and may result from current or past damage to the peripheral nervous system, CNS, or may have no organic cause.1510
Pathophysiology of chronic pain
The exact mechanisms involved in the pathophysiology of chronic pain are complex and remain unclear. A phenomenon called central sensitization16 is said to be responsible for the same. It is believed that following injury or with long continued stimulation, rapid and long-term physiological and structural changes occur within the secondary neurons e.g. spinothalamic or spinoreticular tracts that arise in the dorsal horn and are involved in the transmission and modulation of pain (nociceptive information). This central sensitization leads to chronic pain (Fig. 1.8).
The pain leads to hypersensitivity or hyperexcitability and results in transmission of progressively increasing numbers of pain impulses and an ‘abnormal’ spread of pain.
The patient can feel intense pain in response to a stimulus that is not usually associated with pain, for example, touch.
This abnormal processing of pain within the peripheral nervous system and CNS may become independent of the original painful event and this pain usually does not serve any useful function.
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FIGURE 1.8: Chronic pain pathophysiology
Acute Pain
This is a pain, which occurs in response to tissue injury and is usually short lived, lasting as long as the injurious stimulus exists.
Pathophysiology of acute pain
Acute pain results from activation of the peripheral pain receptors, the A-delta and C-sensory nerve fibers. They travel along the pain pathway in the spinal cord as already described and reach the cerebral cortex
Pain is one of the most common reasons for which individuals visit the doctor. Yet, pain is often undertreated or untreated. It is highly subjective and hence, it is also a challenge for the healthcare provider to evaluate and treat such pain.
Untreated Acute Pain
The effects of untreated acute pain are:
  • Increases metabolic rate
  • Increases cardiac work
  • Interferes with blood clotting
  • Leads to water retention
  • Lowers oxygen levels
  • Impairs wound healing
  • Alters immune function
  • Interferes with sleep
  • Creates negative emotions
  • Delays the return of normal gastric and bowel function in postoperative patients.
Unrelieved acute pain and perhaps the underlying pathophysiology cause it to progress to chronic pain. Acute pain must be recognized before the pain becomes chronic. Once the pain has been established for more than 6 months, the likelihood of complete pain relief is remote.
Untreated Chronic Pain
Chronic pain is different because it may occur without apparent injury/reason, serves no discernible purpose and denies the sufferer the luxury of forgetfulness, which is present in acute pain. Most of the investigations may also be normal. Hence, patients get referred to different specialists, but there is a baffling absence 12of treatable organic causes. When evidence is inconclusive and no diagnosis is possible, the general conclusion is ‘it is all in their head’, i.e. they have a psychological problem.
Patients with chronic pain, when compared to those with almost all other medical conditions, suffer dramatic reductions in physical, psychological and social well-being and their health related quality of life is lower.17 Chronic pain is:
  • Impairs one's ability to have a productive life
  • It dominates, depresses, debilitates and ultimately lowers quality of life
  • Work efficiency comes down
  • Employers also stand to lose due to increased work absenteeism
  • Causes serious economic and social problems.
Chronic pain should be managed by the use of aggressive rehabilitative techniques including interventional techniques, when the pain is either of a non-cancerous origin or when primarily caused by cancer. Chronic pain management requires more effort and resources since it is necessary to address the complex physical, psychosocial and spiritual problems. One must remember that pain relief is a right of the patient. A coordinated team effort is required toward that goal.
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