Acute and chronic pain

• Angelina Jolie: 'Without pain, there would be no suffering, without suffering we would never learn from our mistakes. To make it right, pain and suffering is the key to all windows, without it, there is no way of life'
• Pain


  Not just a sensory modality but an experience
• International Association for the Study of Pain definition of pain

  An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such
• Types of sensation


  • Protopathic (noxious) - pain, subserved by high-threshold receptors and conducted by smaller, lightly myelinated (Aδ) and unmyelinated (C) nerve fibers
  • Epicritic (nonnoxious) - light touch, pressure, proprioception, and temperature discrimination, characterized by low-threshold receptors and is generally conducted by large myelinated nerve fibres
• Nociception


  The neural response to traumatic or noxious stimuli
• Clinical division of pain

  • Acute pain, which is primarily due to nociception
  • Chronic pain, which may be due to nociception but in which psychological and behavioral factors often play a major role
• Other types of pain classification

  • According to pathophysiology (nociceptive or neuropathic pain)
  • According to aetiology (e.g. postoperative or cancer pain)
  • According to the affected area (e.g. headache or low back pain)
• Lance Armstrong: 'Pain is temporary. It may last a minute, or an hour, or a day, or a year, but eventually it will subside and something else will take its place. If I quit, however, it lasts forever'
• Acute pain


  Pain that is caused by noxious stimulation due to injury, a disease process, or abnormal function of muscle or viscera
• Types of acute pain

  • Somatic pain (superficial and deep)
  • Visceral pain (true localized, localized parietal, referred visceral, referred parietal)
• George R.R Martin: 'Some old wounds never truly heal, and bleed again at the slightest word'
• Chronic pain


  Pain that persists beyond the usual course of an acute disease or after a reasonable time for healing to occur, usually defined as pain greater than 3 months
• Examples of chronic pain

  • Pain associated with musculoskeletal disorders (e.g. rheumatoid arthritis and osteoarthritis)
  • Pain associated with chronic visceral disorders
  • Lesions of peripheral nerves, nerve roots, or dorsal root ganglia (including diabetic neuropathy, causalgia, phantom limb pain and post-herpetic neuralgia)
  • Lesions of the central nervous system (stroke, spinal cord injury, multiple sclerosis)
  • Cancer pain
• Pain pathways


  Three-neuron pathways that transmit noxious stimuli from the periphery to the cerebral cortex: primary afferent neurons, second-order neurons, and third-order neurons
• Cranial nerves carrying pain fibers

  • Trigeminal (V)
  • Facial (VII)
  • Glossopharyngeal (IX)
  • Vagus (X)
• Rexed's spinal cord laminae


  The first six lamina make up the dorsal horn and receive all afferent neural activity, representing the principal site of modulation of pain by ascending and descending neural pathways. Second-order neurons are either nociceptive-specific or wide dynamic range (WDR)
• Characteristics of spinal cord laminae

  • Lamina I responds primarily to noxious stimuli from cutaneous and deep somatic tissues
  • Lamina II (substantia gelatinosa) contains many interneurons and plays a major role in processing and modulation of nociceptive inputs from cutaneous nociceptors, has many opioid receptors
  • Laminas III & IV receive primarily non-nociceptive sensory input
  • Laminas VIII & IX make up the anterior (motor) horn
  • Lamina VII is the intermediolateral column containing preganglionic sympathetic neurons
  • Lamina V - visceral afferents terminate primarily in lamina V and to a lesser extent, in lamina I, representing the convergence between somatic and visceral input
• Spinothalamic tract


  The major pain pathway, can be divided into a lateral tract (carrying the discriminative aspects of pain) and a medial tract (responsible for mediating the autonomic and unpleasant emotional perceptions of pain)
• Types of nociceptors


  • Mechanoreceptors, which respond to pinch and pinprick
  • Silent nociceptors, which respond only in the presence of inflammation
  • Polymodal mechanoheat nociceptors, which respond to excessive pressure, extremes of temperature, and alogens (pain producing substances)
• Alogens


  • Bradykinin
  • Histamine
  • Serotonine (5-hydroxytryptamine or 5-HT)
  • H+, K+
  • Some prostaglandins
  • Possibly adenosine triphosphate
• Classification of nociceptors


  • Somatic nociceptors (cutaneous and deep somatic)
  • Visceral nociceptors
• Important neurotransmitters for afferent neurons

  • Substance P
  • Calcitonin gene-related peptide (CGRP)
  • Glutamate
• Peripheral modulation of pain


  Nociceptors and their neurons display sensitization following repeated stimulation, resulting in decreased threshold, increased response frequency, decreased response latency, and spontaneous firing (primary hyperalgesia). Secondary hyperalgesia (neurogenic inflammation) also plays an important role in peripheral sensitization following injury, primarily due to release of substance P from collateral axons
• Visceral nociceptors


  • Less sensitive to noxious stimuli than cutaneous nociceptors
  • Easily sensitized by inflammation
  • Dull and poorly localized pain
• Visceral organs mostly contain silent nociceptors
• The brain lacks nociceptors altogether, however the meningeal coverings do contain nociceptors
• Most important neurotransmitters for afferent neurons

  • Substance P (sP)
  • Calcitonin gene-related peptide (CGRP)
  • Glutamate
• Modulation of pain


  Occurs peripherally at the nociceptor, in the spinal cord, or in the supraspinal structures
• Peripheral Modulation


  1. Nociceptor sensitization

  2. Decrease in threshold

  3. Increase in response frequency

  4. Decrease in response latency

  5. Spontaneous firing (afterdischarges)
• Primary Hyperalgesia


  Mediated by algogens from tissue damage
• Secondary Hyperalgesia (neurogenic inflammation)

  • Due to release of substance P (sP) from collateral axons of the primary afferent neuron
  • Substance P degranulates histamine and 5-HT, vasodilates blood vessels, causes tissue oedema, and induces formation of leukotrienes
• Allodynia


  Pain experienced from a stimulus that would normally go unnoticed, such as skin contact with clothing or a cold breeze
• Hyperpathia


  Increased reaction to a stimulus with subsequent prolongation of painful sensations after the stimulus is removed
• Dyslocalization


  A stimulus in one area produces pain in another area
• Neuralgia


  Pain in the distribution of a nerve or a group of nerves
• Paresthesia


  Abnormal sensation perceived without an apparent stimulus
• Radiculopathy


  Functional abnormality of one or more nerve roots
• Central Modulation


  1. Facilitation (in the spinal cord)

  2. Inhibition
• Segmental inhibition


  In the spinal cord, mediated by glycine and γ-aminobutyric acid (GABA)
• Supraspinal inhibition


  By descending neural activity from supraspinal centers, mediated via α2-adrenergic, serotogenic and opiate (μ, δ, and κ) receptor mechanisms