Pain Physiology Quiz

Pain Perception

• Pain is a complex sensory and emotional experience associated with actual or potential tissue damage. This is defined by the International Association for the Study of Pain (IASP).
• Nociception is the neural response to potentially tissue damaging stimuli.
• Pain occurs when tissues are damaged and the individual reacts to remove the damage.
• Pain is a symptom, subjective, protective, modifiable by developmental, behavioural, personality and cultural factors. Associated signs include crying, sweating, elevated heart rate and blood pressure, behavioral changes.

Types of Pain

• Fast pain: Also called sharp, pricking, acute, or electric pain, it is felt within 0.1 seconds of the stimulus. It is well-localized and not typically felt in deeper tissues.
  • Caused by thin myelinated nerve fibers (A-delta fibers).
• Slow pain: Also called slow burning, aching, throbbing, and nauseous pain, this is chronic pain. It is felt after 1 second or more, and intensity gradually increases over seconds or minutes. It is poorly localized and frequently associated with tissue damage.
  • Caused by unmyelinated nerve fibers (C fibers).

Classification of Nerve Fibers

• Nerve fibers are classified by diameter and speed. Larger diameter fibers transmit signals faster.
• The different types of fibers (Aα, Aβ, Aδ, C) respond to different stimuli, such as temperature, touch, proprioception, pressure, and pain.

Pain Receptors & Their Stimulation

• Pain receptors are free nerve endings that are widespread across skin, somatic tissues, and some internal tissues (e.g., periosteum, arterial walls).
• Pain receptors are stimulated by mechanical, thermal, and chemical stimuli.
• Chemicals like bradykinin, serotonin, potassium ions, histamine, hydrogen ions, lactic acid, acetylcholine (ACh), proteolytic enzymes, leukotrienes, and cytokines can also stimulate pain receptors.
• Prostaglandins and substance P don't directly stimulate receptors, but increase sensitivity (decrease threshold) to other stimuli.

Neurotransmitters of Pain

• Neurotransmitters bathe nociceptors, activating and sensitizing them.
• Prostaglandins and bradykinin sensitize nociceptors to low-intensity stimuli.
• Histamine and serotonin directly induce pain when applied to nerve endings.
• Hydrogen ions and serotonin directly act on ion channels in the cell membrane, and trigger second messenger systems.

Pain Receptors & Their Stimulation (Non-adapting)

• Pain receptors generally do not adapt, meaning the intensity of pain signals increase as stimulus continues. This is especially true for slow pain that is aching, throbbing, nauseous. Excitation of pain fibers becomes progressively greater, increasing the pain sensitivity, a process called hyperalgesia.
• The rate of tissue damage correlates with pain; damage rate is more important than the total damage.

Cause of Pain

• Bradykinin is a major cause of pain after tissue damage.
• Tissue ischemia (reduced blood flow) often leads to pain due to lactic acid accumulation (anaerobic metabolism) and bradykinin, and proteolytic enzymes released from cell damage.
• Muscle spasm can directly stimulate mechanosensitive pain receptors and indirectly lead to ischemia (reduced blood flow) therefore further increasing the rate of metabolism and causing even greater release of pain-inducing substances.

Dual Pain Pathways

• Neospinothalamic: Transmits fast, acute pain (Aδ fibers). Pain signals terminate in lamina I (lamina marginalis), excite a second-order neuron, cross over to the opposite side in the anterior commissure, then travel up the lateral spinothalamic tracts. This pathway is involved in localized, well-localized pain.
• Paleospinothalamic: Transmits slow, chronic pain (C fibers). Signals terminate in laminae II and III (substantia gelatinosa) of the dorsal horns, a second-order neuron is excited, crosses over to opposite side in anterior commissure, ascends the lateral spinothalamic tracts. Involved in poorly localized pain.

Referred Pain

• Pain originating from internal organs (viscera) is sometimes felt in a different site on the body surface.
• Activity in interneurons, part of the anterolateral pathway, stimulates the primary sensory cortex, causing the individual to feel pain in a specific body region.

Referred Pain - Theories

• Convergence theory: High number of peripheral pain afferents (from surface and internal organs) converge onto the same spinothalamic neurons in the spinal cord.
• Facilitatory theory: Somatic and visceral pain afferents connect to related but separate spinothalamic neurons; visceral afferents have collaterals that connect to the spinothalamic neurons receiving somatic pain. This leads to pain impulses traveling up the somatic spinothalamic pathway, causing pain to be felt in the skin.

Pain Perception

• Pain perception involves multiple levels of the nervous system.
• The thalamus is an important center for locating and perceiving pain including intensity. Lesion of the thalamus can cause severe pain (thalamic pain).
• Sensory cortex is necessary for localization of pain (and intensity). Other areas, such as reticular formation, limbic areas, hypothalamus, other subcortical areas help with this.

Process of Pain Physiology

• Transduction: Nociceptive stimuli (noxious stimuli) are converted to electrical energy.
• Transmission: Pain impulses are carried by Aδ or C fibers along the spinothalamic tract.
• Perception: Pain is perceived in the brain, through complex interactions between neurons in higher brain centers.
• Modulation: The CNS controls pain transmitting neurons through inhibition (endogenous opioids).

Pain Modulation/Modification

• Pain modulation is the variability in pain perception, influenced by endogenous and exogenous mechanisms. These can increase or decrease pain threshold.
• Enhancements and inhibitions occur all levels of the nervous system (peripheral nerve, spinal cord, brain sites) influence pain perception.

Pain Modulation (Pain Suppression)

• Pain suppression (analgesia system) involves blocking pain signals through:
• Periaqueductal gray (PAG) and periventricular areas of the mesencephalon and pons
• Raphe magnus nucleus within the pons and the nucleus reticularis in the medulla
• Pain inhibitory complex in dorsal horns of the spinal cord.
• Transmitters such as enkephalin, cause pre- and post-synaptic inhibition of incoming pain fibers (Aδ and C).
• Serotonin releases enkephalin.
• Opioid peptides (endorphins, enkephalins, dynorphin) from hypothalamus, pituitary, and brain stem are involved in the inhibition of pain impulses.

Opioid Actions

• Endogenous opioids (endorphin, enkephalin, dynorphin) and exogenous opioids (morphine, codeine, fentanyl, pethidine, opium, heroin) reduce pain.
• Act presynaptically or postsynaptically, by blocking calcium channels, to prevent pain neurotransmitter release. Leads to hyperpolarization and prevent activity of pain neurotransmitters.
• Activate descending pain modulatory (inhibitory pathway).

Pain Modulation (Gate Control Theory)

• Gate control theory: Non-painful input closes the gates to painful input.
• Substantia gelatinosa (SG) in the spinal cord acts as a gate.
• Stimulation of Aβ fibers (e.g. touch fibers) activates SG, closes the gate to Aδ and C fibers (pain fibers).
• Stimulation of Aδ and C fibers blocks the gate to Aβ fibers.
• Various methods for pain relief (such as massage, counter-irritation, topical application, nerve stimulation, acupuncture) are based on this theory.

Varieties of Pain

• Phantom pain: Pain felt in a limb or body part that has been amputated.
• Psychogenic pain: Pain related to emotional factors, not physical damage.
• Neuropathic pain: Pain caused by damage or disease to the nervous system. This can involve injuries to nerve fibers or vessels supplying them, like diabetes.

Pain in Dentistry

• Pulpal origin pain: Visceral, threshold pain type that responds to all forms of noxious stimuli but not typically associated with the usual masticatory functions. Often does not remain the same but may become chronic or involve structures of the periodontal ligament.
• PDL origin pain: Deep somatic type of pain, more localized than pulpal pain. This pain is closely connected to biomechanical function, localized precisely. Characterized by discomfort during biting under occlusal pressure that causes the tooth to be sore or extended.
• Orofacial pain pathway: The pathway for somatic pain from the oral/facial structures. The trigeminal nerve plays an important role in this pathway.
• Odontic pain pathway: The specific pathway for pain from teeth. The trigeminal nerve is the important pathway to the region of the face and teeth.

Orthodontic Pain Pathway

• First order neurons in the trigeminal ganglia receive nociceptive stimuli and synapse with second-order neurons (trigeminal nucleus caudalis) in the medulla oblongata.
• Second-order neurons decussate (cross over) to the contralateral side and synapse with third-order neurons in the ventroposterior nucleus of the thalamus.
• Third-order neurons project to the somatosensory cortex, leading to pain perception.

Dental Pain of Pulpal Origin

• Visceral in nature, threshold type pain.
• Responds to all types of noxious stimuli.
• Not typically associated with ordinary masticatory function.
• Usually resolves, can become chronic or involve periodontal ligament structures (e.g., periodontal ligament).

Dental Pain of PDL Origin

• Deep somatic pain of musculoskeletal type.
• More localized than pulpal pain.
• Closely related to biomechanical (masticatory functions).
• Receptors in the periodontal ligament are capable of precise localization.
• Pain is often described as discomfort during biting, or soreness under pressure or stretching of the periodontal ligament.