Overview

Definitions

• Pain: 
  • According to the International Association for the Study of Pain (IASP), pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” 
  • Mental suffering or distress
• Nociception: 
  • Noxious (or toxic) stimulus or stimulus that can become noxious with prolonged exposure 
  • Process through which peripheral pain receptors transmit information about current (or potential) tissue damage centrally as pain
• Nociceptor: receptor in end organ that detects biochemical changes associated with current or potential tissue damage
• Hyperalgesia: exaggerated response to noxious stimuli
• Allodynia: sensation of pain in response to an innocuous stimulus

Types of pain

• Physiologic (acute) pain
• Pathologic (chronic) pain
• Nociceptive: 
  • Pain in response to actual or potentially harmful stimuli
  • Often described as aching, localized 
  • Aggravated by movement
• Neuropathic: 
  • Nerve injury or impairment that is associated with allodynia 
  • Often described as radiating, shooting 
  • Independent of movement 

Embryology

• 7 weeks: development of free nerve endings 
• 18 weeks: hormonal stress responses to pain 
• 23–30 weeks: thalamic projections into the somatosensory cortex
• 26 weeks: hemodynamic and behavioral reactions to painful stimuli

Function of pain

• Adaptive measures to minimize and avoid further tissue damage
• Evoked responses:
  • Withdrawal from noxious stimulus (e.g., spinal reflexes)
  • Anticipatory movements (e.g., movement of the arms to protect the eyes and face, bracing before imminent impact)

Visceral Pain

Characteristics

• Poorly localized
• Unpleasant
• Associated with nausea and autonomic symptoms

Nociception process

• Nociceptors in the walls of the viscera are sensitive to distention and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the organ → receptor and action potentials are evoked:
  • Pain shifts in intensity when produced in peristaltic structures (e.g., intestines).
  • Pain may be sharp upon contraction and dull upon relaxation.
• The action potentials are carried by afferent fibers via sympathetic and parasympathetic nerves of the myenteric plexus.
• The signal is transmitted to the neural bodies in the dorsal (and cranial) nerve ganglia → signal continues to the dorsal horn of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord.
• Convergence-projection theory: visceral afferent fibers converge with somatic afferent fibers on the same neural bodies in the dorsal horn → the signal is sent through the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord to the thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus and the somatosensory cortex.
• Pain is perceived to come from the somatic structure corresponding to the somatic fibers that converged with the visceral fibers (referred pain).
  • For example: 
    • Pain in MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction is referred to the left upper limb.
    • Pain due to ureteral distention is referred to the corresponding testicle in men.
  • There may also be motor/sudomotor manifestations in somatic structures related to the corresponding spinal segment mediated by spinal interneurons.
    • In the osteopathic literature, this manifestation is referred to as facilitation or a viscerosomatic reflex.
    • Example: muscle spasm, fascial restriction in the paraspinal musculature at a spinal level corresponding to visceral dysfunction

Peripheral versus Central Sensitization

Peripheral sensitization

• Results from persistent or repetitive peripheral nociception (traditional inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation) or nerve injury
• Hyperstimulation or damage to the 1st-order neuron alters the electrical traits and elaboration of neurotransmitters (e.g., SP, CGRP, NGF).
• The inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and the initial injury combine to create an enhanced pain sensation and perpetuates the pain response: 
  • Neuropathic pain may develop in an area devoid of nerve injury.
  • May manifest with hypersensitivity, hyperalgesia, allodynia.

Central sensitization

• Phenomenon thought to occur centrally, perhaps at the level of the rexed laminae
• Generally a progression from peripheral sensitization but may also be produced without any known peripheral stimulus or a CNS insult.
  • Segmental central sensitization: neuroplastic changes that occur in response to a physical injury that cause constant activation of the pain pathway (i.e., progression from central sensitization)
  • Suprasegmental central sensitization: neuroplastic changes in brain sites of the pain pathway with or without known injuries (from CNS injury).
• Often occurs in the setting of CNS insults (e.g., stroke, spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord injury)
• Often associated with psychiatric conditions:
  • Anxiety disorders
  • Mood disorders (e.g., depression)
  • Sleep disorders
  • Somatization disorder
• May occur as a primary disorder (e.g., fibromyalgia Fibromyalgia Fibromyalgia is a chronic pain syndrome characterized by widespread body pain, chronic fatigue, mood disturbance, and cognitive disturbance. It also presents with other comorbid symptoms such as migraine headaches, depression, sleep disturbance, and irritable bowel syndrome. Fibromyalgia) 

The Gate Control Theory of Pain

• A physiologic sensory “gate” exists at the level of the dorsal horn in any given spinal segment (or cranial nerve nucleus).
  • Only so much sensory information can get through the gate at any given time.
  • Preferential passage through the gate is granted to incoming sensory signals conducted by larger, more heavily myelinated, faster-conducting nerve fibers.
  • An open gate is a dorsal horn receiving isolated noxious (painful) stimulus.
  • A closed gate is a dorsal horn receiving simultaneous physical (nonnoxious) physical stimuli. 
• Incoming pain signals are largely conducted by A-delta (relatively slow-conducting) and type C (slow-conducting) fibers, while A-alpha and A-beta (fast-conducting) fibers carry nonnoxious physical stimuli (e.g., movement, vibration, pressure, temperature, electrical stimulation).
  • This distinction becomes very important when painful (noxious) and other physical stimuli (nonnoxious) are simultaneously applied in the receptive field of a peripheral nerve. 
  • Nonnoxious physical stimuli (conducted by faster, larger, more heavily myelinated fibers) are given preferential passage through the gate, lessening or eliminating the incoming pain (noxious) stimulus.
• Humans unknowingly apply this concept on a daily basis to relieve trivial noxious insults. For example:
  • Scratching (nonnoxious physical stimulus) a mosquito bite (noxious chemical stimulus) to relieve the itch (pain)
  • Rubbing (nonnoxious physical stimulus) the elbow (“funny bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones”) after bumping it on a door frame (noxious physical stimulus) to relieve the pain
• The “pain team” purposefully applies this concept to treat pain nonpharmacologically:
  • Massage
  • Physiotherapy
  • Peripheral nerve stimulation
  • Spinal cord stimulation

Clinical Relevance

• Chronic pain: pain that extends beyond the expected period of healing (> 3 months), with an underlying pathology that is insufficient to explain the presence or extent of the pain. Chronic pain can disrupt sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep, daily activities, and psychosocial function. Chronic pain is commonly seen in individuals with malignancies and requires a very personalized management approach.
• Pain management Pain Management Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a subjective experience. Acute pain lasts < 3 months and typically has a specific, identifiable cause. Pain Management: Today, medical professionals have myriad—both pharmacologic and nonpharmacologic—options to alleviate pain. The specific management strategy followed depends on the type of pain and the individual’s circumstances, perspective, and underlying condition. 
• Complex regional pain syndrome ( CRPS CRPS Complex regional pain syndrome (CRPS) is a chronic regional neuropathic pain condition characterized by excruciating pain (out of proportion to apparent tissue damage or inciting trauma), paresthesia, allodynia, temperature abnormalities, skin discoloration, edema, reduced range of motion, and bone demineralization. Complex Regional Pain Syndrome (CRPS)): condition characterized by excruciating pain that is out of proportion to the inciting event and is accompanied by allodynia, temperature abnormalities, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin discoloration, and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, among other findings. This syndrome affects women more often than men and is often incited by trauma. Diagnosis is clinical, supported by the Budapest Consensus. Complex regional pain syndrome is closely related to litigation of work-related issues, requiring special care by the physician.