Pain Mechanisms in Physiology

Pathway Theory and Pain

• Pathway theory and pain are interconnected
• Understanding pain involves understanding the pathway it takes through the body
• Key elements of pain include nociceptors, spinal ganglia, and the lateral spinothalamic tract.

Pain Perception and Types

• Nociceptors are pain receptors (receptors)

• Pain is a protective mechanism

• Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage

• Two main types of pain: fast pain and slow pain.

• Fast pain is sharp and acute, while slow pain is lingering or throbbing.

• Fast pain is located precisely and felt quickly. Slow pain is poorly localized.

• Fast pain is elicited by mechanical and thermal stimuli

• Slow pain results from a combination of mechanical, thermal, and chemical stimuli

Nerve Fiber Classification

• Nerve fibers are categorized by size (diameter) and myelination (presence of a fatty sheath).
• Larger myelinated fibers transmit signals faster than smaller, unmyelinated ones
• Different nerve fibers carry different types of sensory information

Pain Receptors and Their Stimulation

• Pain receptors are free nerve endings
• They're widespread across the body, except in the brain, and in internal tissues like arteries
• Stimuli can include mechanical, thermal, or chemical types.
• Chemicals can include bradykinin, serotonin, K+ ions, histamine, H+, lactic acids, ACH, proteolytic enzymes, leukotrienes, cytokines, and capsaicin
• Prostaglandins and substance P sensitize nociceptors.

Pain Receptors and Their Stimulation - Continued

• Pain receptors adapt to stimuli, becoming less sensitive or more sensitive over time if the stimuli continues
• Pain resulting from heat above 45 degrees Celsius is closely related to the rate of tissue damage, not the overall amount of damage
• Intensity of pain corresponds to the rate of tissue damage from varied causes (such as bacterial infection or ischemia).

Neurotransmitters of Pain

• Neurotransmitters are chemicals that transmit signals between nerve cells.
• Neurotransmitters involved in pain include histamine, substance P, ATP, H+, 5-HT, 4-HNE, bradykinin, and prostaglandins.
• They activate and sensitize nociceptors when they are released
• These molecules work in a complex system to create pain perception.

Causes of Pain

• Tissue damage is a leading cause of pain, and the intensity of the pain often correlates with the extent of tissue damage
• Tissue ischemia (reduced blood flow) also causes pain, often intense and with the degree of pain increasing in direct correlation to the metabolism rate
• Muscle spasms can trigger pain both directly, by stimulating mechanosensitive receptors, and indirectly, by compressing blood vessels and increasing ischemia

Dual Pain Pathways: Neospinothalamic

• The neospinothalamic pathway is for fast pain transmission.
• It involves first-order neuron termination in lamina I of the dorsal horn, then excites second order neurons of the neospinothalamic tract.
• Glutamate is the principle neurotransmitter.
• The pathway crosses to the opposite side of the spinal cord and ascends through the anterolateral columns,
• Ultimately leading to the thalamus where the pain is further processed.

Dual Pain Pathways: Paleospinothalamic

• The paleospinothalamic pathway is for slow pain transmission.
• First order neurons, or C fibres, synapse in the substantia gelatinosa, or laminae II and III in the dorsal horn
• Neurotransmitters are primarily substance P.
• The impulse decussates and travels through the spinothalamic tracts to eventually reach various locations in the brain.

Referred Pain

• Referred pain arises from an internal organ but is perceived in a different body region.
• It occurs because nerve pathways from the organ and the referred site overlap at the spinal cord level
• There are many diverse examples of referred pain that can occur.

Referred Pain - Theories

• Convergence theory describes overlapping pain pathways at the spinal cord level.
• Visceral and somatic pain input can thus trigger the perception of pain in the skin.
• Another perspective is the facilitator theory, which suggests that visceral pain signals can activate somatic pain pathways, potentially causing pain in the skin

Pain Perception - Aware of Pain

• Pain perception occurs in multiple locations and stages in the brain.
• The thalamus is critical for pain perception as it directs the sensory information.
• The cortex, reticular formation, limbic areas, and the hypothalamus have implications in pain perception. The stimuli are interpreted as pain

Process of Pain Physiology

• Transduction turns noxious stimuli into electrical energy
• Transmission of this electrical energy occurs through peripheral nerve fibers (nociceptors). These receptors then carry the impulse.
• Perception of pain occurs when this impulse reaches the brain's cortex, triggering a response
• Modulation occurs as the CNS regulates pain signals through inhibition.

Pain Modulation/ Pain Modification

• Pain modulation refers to the variable nature of pain perception.
• Pain modulation depends on both endogenous and exogenous factors which can modify pain perception or increase/decrease pain thresholds
• The nervous system plays a crucial role in regulating pain

Pain Modulation (Pain Suppression)

• Pain suppression involves the analgesia system which blocks pain signals through different parts of the brain and spinal cord
• Included in this process are the periaqueductal gray and the periventricular areas, as well as the nuclei of the medulla oblongata
• Pain signal suppression happens as enkephalin, serotonin, and other substances suppress incoming pain fibers in particular parts of the nervous system

Opioid Actions

• Opioids (including endogenous and exogenous types) affect pain perception by various mechanisms
• They block calcium channels and reduce calcium influx, essentially shutting down pain neurotransmitter release
• They open potassium channels triggering efflux and hyperpolarization which reduces pain neurotransmitter activity
• Activation of descending pain pathways and inhibition of GABA pathways are also effects that opioids have

Pain Modulation (Gate Control Theory)

• Gate control theory suggests that non-painful stimuli can close the "gates" to pain signals in the spinal cord by activating certain nerve fibers.
• This modulation of pain signals occurs in the substantia gelatinosa of the spinal cord.
• Different types of stimuli can stimulate various parts of the nervous system, potentially alleviating pain.

Varieties of Pain

• Phantom pain is felt in a missing limb (or other removed body part), with no stimulus to trigger the sensation.
• Psychogenic pain stems from emotional factors, unlike physical pain.
• Neuropathic pain originates from damage to the nervous system, as opposed to musculoskeletal harm, with repetitive stimulation as a potential cause

Pain in Dentistry

• Dental pain can be categorized into fast (and acute) pain and slow (and more chronic) pain
• Fast pain is caused by stimuli like temperature changes, drilling, and air; slow pain is associated with inflammation and tissue damage
• Different types of pain in the mouth have corresponding pathways and stimuli triggers, which differ based on the origin of the pain.

Dental Pain of Pulpal Origin

• Pain of pulpal origin is of a visceral type and generally less precisely localized.
• It does not persist indefinitely, but can become chronic
• Pain often stems from the pulp tissue of a tooth

Dental Pain of PDL Origin

• Pain originating from the periodontal ligament (PDL) is distinct in being more localized and closely linked to musculoskeletal function.
• It's often triggered by occlusal pressure or biting and felt as soreness or elongation.

Orofacial Pain Pathway

• Orofacial pain pathways stem from the trigeminal nerve (CN V), not the spinal nerves.
• The pathway from the face/oral structures relays signals to the brain.
• Orofacial pain has a distinct pathway from other types of pain.

Orthodontic Pain Pathway

• The pathway for orthodontic pain is similar but begins with trigeminal neurons in the trigeminal ganglia. Nociceptors send signals via the trigeminal nucleus caudalis in the medulla oblongata up to the thalamus and eventually to the cortex, where it is interpreted.

Dental Pain of Pulpal Origin

• Visceral in character
• Low threshold pain type
• Responds to different stimuli for pain
• Non-localized pain
• Often not persistent, can become chronic

Dental Pain of PDL Origin

• Deep somatic pain with a musculoskeletal link
• More localized than pulpal pain
• Linked to mechanical functions (mastication)
• PDL receptors are sensitive to precise localization via occlusal pressure.