Page 1: Introduction

• Title: Provided for your own use

• Notes:

  • Document meant for personal study.

  • Not intended for distribution or web posting.

  • Includes a mid-module survey requesting completion.

Page 2: Course Information

• Course: MB3057 Topic-4 Pain and Pain Management

• Instructor: Prof DG Lambert

• Contact: DGL3@le.ac.uk

• Location: Hodgkin Building, 3rd Floor, University of Leicester

Page 3: Learning Objectives - Lecture 1

• Epidemiology of Pain: Understand pain types and prevalence.

• Nociceptive Signal Processing: Describe mechanisms including:

  • Transduction

  • Afferent Inflow

  • Spinal Gating

  • Perception

  • Descending Inhibitory Control

• Pain Sensitization: Define and explore the concept of pain sensitization.

Page 4: Definition of Pain

• Definition: An unpleasant sensory and emotional experience connected to actual or potential tissue damage.

• Key Points:

  • Individual experience influenced by biological, psychological, and social context.

  • Distinction between pain and nociception; pain cannot be solely inferred from sensory neuron activity.

  • Pain perception is learned through life experiences.

  • Respect individuals' reports of pain, regardless of ability to communicate.

  • Adaptive in nature but can negatively affect function and well-being.

  • Various expressions of pain exist beyond verbal communication.

Page 5: Acute Pain - Prevalence

• Statistics:

  • Acute pain leads to medical consultation; >50% of the population will seek help over their lifetime.

  • British Pain Society (2005) indicates 10 million experience daily pain in Great Britain.

  • 49% of individuals with pain report taking time off work.

Page 6: Chronic Pain - Prevalence

• Statistics:

  • Approximately 15.5 million (34% of England's population) live with chronic pain.

  • Common causes include musculoskeletal conditions like osteoarthritis, back, and neck pain.

• Disparities:

  • Higher prevalence of chronic pain in women, minority ethnic groups, and among disadvantaged demographics.

  • Increase in chronic pain cases in young adults noted between 2011 and 2017.

Page 7: Pain Management Market

• Market Overview:

  • Global pain management drugs market projected to reach US$ 52.1 billion by 2024, up from US$ 38.9 billion in 2018.

Page 8: Characteristics of Acute Pain

• Survival Value:

  • Acute pain serves as an important survival mechanism.

• Illustrative Links:

  • Links provided to resources depicting examples of acute pain presentations.

Page 9: Nociceptive Pain

• Key Concept:

  • Nociceptive pain serves a critical role in survival and protection against injury.

Page 10: Pain Pathway Overview

• Neural Pathways:

  • First order neurons transmit signals to second order neurons via neurotransmitters.

  • Third order neurons convey nociceptive impulses to the cerebral cortex, leading to pain perception.

  • Descending controls from the midbrain and brainstem enhance modulation of pain transmission.

Page 11: Nociceptors and Transduction

• Nociceptors:

  • Free dendritic nerve endings categorized into three types based on stimuli:

    • Chemical: Exogenous (external) and endogenous (internal) agents provoke responses.

    • Mechanical: Respond to mechanical pressure and distension.

    • Thermal: Sensitive to extreme temperatures.

Page 12: Mechanical and Thermal Receptors

• Mechanisms:

  • Mechanical receptors react to skin distension and inflammation pressures.

  • Thermal receptors respond to extremes in hot or cold temperatures.

Page 13: Response to Noxious Stimuli

• Polymodal Nociceptors:

  • Can react to a variety of noxious stimuli types.

  • Ability of nociceptors to transduce different energy forms; associated with various receptor structures.

Page 14: Molecular Transduction Targets

• TRPV1 Receptor:

  • Central in the pain pathway; integral to polymodal characteristics.

  • Involvement of bradykinin, prostaglandin receptors, and ion channels in pain processes.

Page 15: TRPV1 Receptor Features

• Description:

  • A ligand gated ion channel with 838 amino acids, multiple subunits; preferential permeability to Ca2+.

  • Critical in transmitting pain signals; responds to various stimuli.

Page 16: TRPV1 Activation Mechanisms

• Mechanism:

  • Activation leads to depolarization and generation of action potentials indicating pain sensations.

  • Involvement of various activators including heat, acidity, and capsaicin.

Page 17: TRPV1 as a Pain Integrator

• Research Reference:

  • Highlighting TRPV1 role in inflammatory pain and hyperalgesia; insights into pain pathways.

Page 18: Peripheral Upregulation of TRPV1

• Relevance:

  • TRPV1 levels increase in inflammatory conditions, contributing to hyperalgesia and sensitization.

Page 19: Pathways of TRPV1 Expression

• Peripheral Mechanisms:

  • TRPV1 expression modulation in response to injury and inflammation affecting heat sensitivity and pain perception.

Page 20: Nociceptive Pathway Conduction

• Neural Transmission:

  • Nociceptors synapse in the spinal cord, with ascending pathways transmitting signals to brain regions responsible for pain perception.

Page 21: Afferent Inflow Wiring

• Nerve Fibers:

  • Nociceptive afferents primarily consist of C-fibres and Aδ-fibres, each responding to specific stimuli and conducting pain differently.

Page 22: C-fibre Characteristics

• Features of C-fibres:

  • Small diameter, unmyelinated, slow conduction velocity; associated with dull or aching pain and polymodal responses.

Page 23: Aδ-fibre Characteristics

• Features of Aδ-fibres:

  • Myelinated with faster conduction; related to sharp pain sensations; largely mechanosensitive.

Page 24: Spinal Gating Mechanisms

• Pain Gatekeeper:

  • Specific laminae in the dorsal horn serve as synaptic sites for nociceptive processing and transmission.

Page 25: Dorsal Horn Organization

• Functionality:

  • Termination and synapse of C and Aδ-fibres in laminae I, II, and V influence pain transmission pathways via inhibitory interneurons.

Page 26: Substantia Gelatinosa Role

• Inhibitory Function:

  • Interneurons in this area mediate inhibition between primary and second order nociceptive afferents, impacting pain perception.

Page 27: Gate Control Theory Summary

• Hypothesis:

  • Proposed differential regulation of nociceptive signaling by SG neurons based on the nature of signals received, leading to open or closed gates depending on the nociceptive or non-nociceptive signaling.

Page 28: Physiology of Pain Control

• Descending Control Mechanisms:

  • Involvement of specific brain areas that modulate pain perception and response via various neurotransmitters and opioids.

Page 29: Somatosensory Cortex Overview

• Anatomical Relevance:

  • Description of the brain regions involved in sensory processing and their disproportionate representation in the somatosensory homunculus.

Page 30: Modulatory Mechanisms Overview

• Key Areas:

  • Periaqueductal gray plays a significant role in modulating descending pathways and enhancing inhibitory output to pain signals.

Page 31: Inhibitory Controls and Opioids

• Mechanisms:

  • PAG and locus ceruleus contribute to pain modulation; electrical stimulation highlights the potential for opioid manipulation in pain relief.

Page 32: Pain Assessment Methods

• Animal Studies:

  • Various methods for assessing pain responses in laboratory settings, indicative of pain sensitivity and response.

Page 33: Von Frey Filaments Usage

• Tool Description:

  • Application of Von Frey filaments for mechanistic testing of pain thresholds in both human and animal subjects.

Page 34: Peripheral Sensitization Mechanisms

• Tissue Damage Response:

  • Injury leads to inflammation, attracting immune cells and releasing mediators that heighten pain sensitivity.

Page 35: Mechanisms of Peripheral Sensitization

• Mediators:

  • Various chemical substances released contribute to the overall sensitization process, enhancing primary afferent activity.

Page 36: Central Sensitization Mechanisms

• Definitions:

  • Tissue and nerve injury leads to long-term neuron changes, resulting in hyperalgesia and allodynia due to persistent stimulation.

Page 37: Inflammation's Role in Sensitization

• Impact:

  • Inflammation leads to both peripheral and central sensitization, affecting pain processing.

Page 38: Pathophysiology Insights

• Hyperalgesia and Allodynia:

  • Definitions and distinctions; hyperalgesia involves increased responses, while allodynia covers pain from normally non-painful stimuli.

Page 39: Pain Response Dynamics

• Sensitivity Measurements:

  • Chronic stimuli can lead to sustained alterations in pain sensitivity, with implications for treatment and understanding of chronic pain.

Page 40: Summary of Pain Concepts

• Key Takeaways:

  • Pain transmission pathways are well-defined; the spinal cord functions as a crucial gatekeeper, with modulation possible through descending controls.

  • Importance of understanding these pathways for effective diagnosis and treatment strategies in pain management.

Page 41: Learning Objectives for Lecture 2

• Topics to Explore:

  • Differences between acute and chronic pain.

  • Understanding pathophysiology of various pain types including inflammatory, neuropathic, and cancer-related pain.