Pain, Nociception, and Analgesia Overview

Pain, Nociception, and Analgesia

• Pain is the conscious appreciation of a tissue-damaging stimulus.
• Nociception is the physical process of detecting and transmitting noxious stimuli.
• Nociceptors are structures that detect noxious stimuli.
• Algesia is the induction of the condition leading to nociception and pain.
• Analgesia is the reduction or prevention of either nociception or pain without loss of consciousness.

Lecture Summary

• Pain and nociception: Detection of noxious stimuli, transmission to spinal cord and brain, sensitization/modulation of nociceptors, transmission at spinal level, regulation of nociception.
• Opioid analgesia: Methods of pain relief using opioids.
• NSAIDS analgesia: Methods of pain relief using NSAIDS.
• Other analgesics: Other methods of pain relief.
• Nociception vs exaggerated sensory transmission: Nociceptors are distinct from other sensory receptors - differing conduction velocities, activation thresholds, projection sites, and physiological responses in dorsal horn neurons. Information also ascends through different pathways.

Definitions

• Pain: The subjective conscious appreciation of stimuli that cause or threaten to cause tissue damage.
• Nociception: The physical process of detecting and transmitting noxious (damaging or potentially damaging) stimuli.
• Nociceptors: Structures that detect noxious stimuli. The receptors are located in skin/viscera (e.g. free nerve endings, polymodal nociceptors, mechanical nociceptors). In the skin, nociceptors are located in hairy skin and glabrous skin.
• Algesia: A condition causing nociception and pain.
• Analgesia: Reduction, or prevention of either nociception or pain, without loss of consciousness.

Pain (Nociceptive) Fibres and Receptors

• Types of nociceptors: Polymodal (respond to high-intensity mechanical, thermal, and chemical stimuli) and mechanical (respond to high-intensity mechanical and strong thermal stimuli) nociceptors.
• Receptive fields: Nociceptors have receptive fields; polymodal receptors have both receptive field 1 & 2.
• Location: Free nerve endings, Merkel's disks, Meissner's corpuscles, Pacinian corpuscles, Ruffini's endings. These are part of the somatosensory system.
• Aδ fibers and C fibres mediate fast and slow pain respectively.
  • Fast pain = sharp, well-tolerated.
  • Slow pain = burning, aching and poorly tolerated.

Somatosensory Afferent Fibres

• Sensory Function (e.g. proprioception, touch, pain, temperature and itch). Nociception is one type of sensory function.
• Types of Receptor (e.g. Muscle spindle, Merkel, Meissner, Pacinian and Ruffini cells, free nerve endings).
• Afferent axon types (e.g. Ia, II, Aβ, Aδ, and C).
• Axon diameter and conduction velocity varies between the different axon types.

Nociception Process

• A noxious stimulus triggers primary transduction (e.g. channel opening).
• This is then passed on to a sensory receptor, which causes a subsequent secondary transduction.
• A change in membrane voltage occurs, then depolarization and action potential generation.
• The action potential travels along primary afferent axons (Aδ and C fibers).
• At the spinal cord, transmitter release occurs.
• Second-order neurons respond.

Signal Detection in Nociceptors

• Nociceptors: Use ion channels to detect noxious stimuli (e.g. ASIC, P2X3, VGNa, VR-1/TRPV-1).

Is Nociception just exaggerated sensory?

• No. Nociceptors exhibit unique properties, including slower conduction velocities, different activation thresholds, different projection sites in the spinal cord, varied physiological responses, and distinct ascending pathways.

Discriminating Thermoreceptors v Thermal Nociceptors

• Thermoreceptors have a threshold for detecting temperature.
• Nociceptors have a threshold for detecting noxious stimuli. Note that the mechanisms of activation can involve similar channels.

Activation Profiles

• Thermoreceptors and thermal nociceptors fire at different frequencies depending on the temperature.

Graded Potentials in Nociceptors

• Nociceptors respond to stimuli of different intensitities by producing graded potentials rather than action potentials.

Nociception and Sensory (Touch) Perception

• These processes involve different types of receptors and differ in conduction velocities, activation thresholds, sites of projection, and responses in dorsal horn neurons, & transmission pathways.

Altered Detection of Pain

• Hyperalgesia: Increased sensitivity to noxious stimuli.
• Allodynia: Painful response to normally non-noxious stimuli.
• Possible sites: Peripheral and central sensitization (e.g. peripheral nociceptors and spinal cord).

Nociceptor Sensitization

• Nociceptors can become sensitized by inflammation (chemicals like histamine and bradykinin).

Modulation of Nociception

• Nociception can be modulated by different factors, which can include nerve growth factor (NGF), prostanoids, bradykinin, and histamine.
• Inhibitory mechanisms exist for modulating pain (e.g. potassium channels and opioid/cannabinoid receptors).

Itch

• Afferent input involves Aδ and C fibres from free nerve endings.
• Inflammation, particularly histamine, can evoke an itch response.
• Analgesics typically don't inhibit itch, but scratch can inhibit itch due to mechanical (almost nociceptive stimulation).

Somatosensory Transmission

• Dorsal root: Sensory information enters the spinal cord via the dorsal root.
• Ganglion cells: Sensory neurons have cell bodies located in the dorsal root ganglion.
• Peripheral receptors: Sensory detection occurs at the peripheral receptors.

Spinal Projection Sites

• Different fibres project to different parts of the spinal cord.
• Nociceptors project to the dorsal horn.

Ascending Pain Pathways

• Pain information travels up to the brain via different tracts (e.g. spinothalamic, spinomesencephalic,spinoreticular tracts).
• Some pain pathways also involve the somatosensory cortex, insular cortex, and anterior cingulate cortex.

Sensory and Nociceptive Pathways

• Sensory and nociceptive pathways vary (e.g. different tract systems) in the spinal cord.

Referred Pain

• Nociception can display a referred pain phenomenon where pain from deeper tissues is felt in the skin.

This quiz explores the concepts of pain, nociception, and analgesia, covering key definitions and the physiological processes involved. It examines the roles of nociceptors, methods of pain relief including opioids and NSAIDs, and the differences between nociception and other sensory transmissions. Test your knowledge on this critical aspect of human physiology.