Pain Care Essentials and Innovations E-Book

Sanjog Pangarkar, Quynh G. Pham, Blessen C. Eapen, Sanjog Pangarkar, Quynh G. Pham, Blessen C. Eapen

• Publisher: Elsevier
• Year: 2020
• eBook ISBN: 9780323722179
• Topic: Medicine
• Subtopic: Physiotherapy, Physical Medicine & Rehabilitation

Covering the newest trends and treatments in pain care, as well as the pain treatment strategies that have been successfully employed in the past, Pain Care Essentials and Innovations brings you fully up to date with effective treatments for acute and chronic pain. It offers expert guidance on both interventional and non-interventional strategies, provided by respected academic physiatrists who practice evidence-based medicine at UCLA and an ACGME-accredited rehabilitation and pain program.- Covers cannabinoids in pain care, novel therapeutics in pain medicine, and integrative care in pain management.- Discusses relevant basic science, psychological aspects of pain care, opioids and practice guidelines, geriatric pain management, and future research in the field.- Consolidates today's available information and guidance into a single, convenient resource.

Chapter 1

Basic Science of Pain

Casey J. Fisher, MD, Tony L. Yaksh, PhD, Kelly Bruno, MD, and Kelly A. Eddinger, BS, RVT

Abstract

This chapter is an overview of anatomy involved in the processing of nociceptive stimuli, the fundamentals of systems underlying acute nociception and persistent pain states, and the linkage to chronic pain and how the immune system plays a role in this processing. The anatomy will be detailed from the most peripheral primary nerve afferents to the secondary neurons including wide dynamic range neurons and also the tertiary projections to the brainstem and cortex. The fundamentals of the physiology of acute pain and persistent pain will be discussed including peripheral and central sensitization as well as neuropathic pain. The role of the immune system involvement in the processing of pain and also how this may affect the transition from acute to chronic pain, including how the Toll-like receptor 4 may be a potential driver of the transition from acute to chronic pain, will be covered.

Keywords

Central sensitization; Neuropathic pain; Peripheral sensitization; Primary nerve afferents; Toll-like receptor 4 (TLR4); Wide dynamic range neurons (WDR)

Introduction

Clinically, the most commonly referenced definition of pain initially described by Harold Merskey in 1964, and as adopted by the International Association in the Study of Pain in 1979, defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” ¹ In this chapter, we will give an overview of the pathways involved in pain processing as it occurs in both the central and peripheral nervous systems as is currently conceived. This overview will include: anatomy involved in the processing of nociceptive stimuli; the fundamentals of systems underlying acute nociception and persistent pain states; and the linkage to chronic pain and how the immune system plays a role in this processing.

Peripheral Anatomy

Primary Afferents ^2–4

The signal of acute nociceptive pain is propagated along sensory neurons, which have cell bodies (somas) that lie in the dorsal root ganglia (DRG) and send one of their axon projections to the periphery and the other to the dorsal horn of the spinal cord in the central nervous system. The axons of peripheral afferents can be classified by anatomical characteristics (Erlanger-Gasser), Conduction Velocity (Lloyd-Hunt), and by their respective thresholds for activation. Most commonly, they are known by anatomical classification into two types of A fibers (β and δ) and C fibers.

C fibers are small, unmyelinated, and therefore, slow conducting fibers (<2 m/s). These primary sensory afferent neurons represent the majority of afferent fibers found in the periphery and are most commonly high threshold fibers, meaning they are not activated unless the stimulus (thermal, mechanical, or chemical) is at an intensity sufficiently high enough to potentially cause tissue injury. As nociceptors, or receptors that detect noxious stimuli, they are triggered to discharge when the range of temperature or pressure corresponds to what would be considered painful. The distal terminals of these small C fibers display large branching dendritic trees and are characterized as being “free” nerve endings. These nerve endings can be activated further by many specific agents in the periphery in response to tissue injury, inflammation, or infection in a concentration-dependent fashion. Table 1.1 depicts the source and nature of these agents as well as the eponymous receptor on C fibers that is activated with each agent. The fact that there are multiple stimulus modalities for these C fibers that can lead to a signal of pain is the reason they are known as C-polymodal nociceptors. In fact, C fibers can be characterized further by what provokes them to fire. There are some C fibers that do not respond to mechanical stimulation. These so-called silent nociceptors, or mechanically insensitive afferents (MIAs), only respond to very high levels of nonphysiologic mechanical stimulation and/or heat. However, they can acquire sensitivity in the face of pathology, such as inflammation, which leads to a sensitized state and activation by relatively low-intensity mechanical/thermal stimuli.

Like C fibers, A-δ fibers are small and can be high threshold. But, A-δ fibers are myelinated, and therefore, faster, with conduction velocity between 10 and 40 m/s. As such, A-δ fibers act as nociceptors and mediate “first” or “fast” pain, whereas C fibers are responsible for “second” or “slow” pain. To put this in context, consider what happens when you touch a hot object. Your immediate reaction is to pull your hand away, which is mediated by noxious thermal sensation activating fast conducting A-∂ afferents. Typically, there is also a slower sensation of pain traveling over the slowly conducting C fibers, which relay tissue damage in the form of a burning sensation. Some populations of A-δ fibers can also be lower threshold at times, meaning they begin to discharge when the range of temperature or pressure corresponds to what would be nontissue damaging. In the case of thermal stimulus, it would be considered a mildly noxious warm/hot sensation. In the case of mechanical stimulus, it would be considered touch or pressure that is borderline painful. A-δ fibers also differ from C fibers in that they express specialized nerve endings that serve to define their response characteristics. This relationship will be delineated further in the peripheral physiology section.

Table 1.1

Summary of Agents, Tissue Source, and Receptors Found at C Fibers ¹² .

Agents	Tissue Source	Receptors
Amines	Mast cells (histamine) Platelets (serotonin)	H1 5HT3
Bradykinin	Clotting factors (bradykinin)	BK 1, BK2
Lipidic acids	Prostanoids (PGE2), leukotrienes	EP
Cytokines	Macrophages (interleukins, tumor necrosis factor)	IL-1, TNFR
Primary afferent peptides	C fibers [substance P (SP), calcitonin gene-related peptide (CGRP)]	NK1, CGRP
Proteinases	Inflammatory cells (thrombin, trypsin)	PAR3, PAR1
Low pH or hyperkalemia	Tissue injury [(H+), (K+), adenosine]	ASIC3/VR1, A2
Lipopolysaccharide (LPS), formyl peptide	Bacteria (LPS, formyl peptide)	TLR4, FPR1

In contrast, A-β fibers are large, myelinated fibers with the fastest conduction velocity (>40 m/s) of primary afferent neurons. They are low threshold afferent fibers that fire in response to low threshold mechanical stimulation, such as touch or pressure. Under normal physiologic states, activation of these afferents does not generate a noxious sensation. However, there are certain conditions in which these afferents initiate a pain sensation, or allodynia. The definition of allodynia is low-intensity tactile or thermal stimuli causing a pain state. This can occur in scenarios where there is nerve damage (for example, carpal tunnel or sciatic nerve lesions).

All of the afferent nerve fibers share the following important characteristics related to the pattern in which they respond to a stimulus and the manner in which they fire:

• i) Afferent nerve fibers display little or no spontaneous firing. They do not spontaneously discharge like other nerve cells of the brain or heart;
• ii) Peripheral afferents typically display a monotonic increase in discharge frequency that covaries with stimulus intensity. This means that if the thermal or mechanical intensity increases, there will be a monotonic increase in discharge frequency because there will be a greater depolarization of the terminal, which will increase frequency of axon discharge; and
• iii) Afferents serve to encode modality by being able to transduce thermal, mechanical, and/or chemical signals into a depolarization based on their individual nerve ending transduction properties. For the larger A-β fiber afferents, the nerve endings are highly specialized, e.g., Pacinian corpuscle, and only respond to specific low threshold stimuli, whereas the free nerve endings of the small C fibers respond to a more diverse array of signals at higher threshold.

Somatic and Visceral Afferents ^{4 , 5}

The location of peripheral afferents is also important when it comes to the type of pain sensation. Peripheral afferent a...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• List of Contributors
• Preface
• Acknowledgments
• Chapter 1. Basic Science of Pain
• Chapter 2. Headache
• Chapter 3. Central Pain Syndromes
• Chapter 4. Visceral Pain: Mechanisms, Syndromes, and Treatment
• Chapter 5. Neuropathic Pain
• Chapter 6. Musculoskeletal Pain
• Chapter 7. Palliative Care and Cancer Pain
• Chapter 8. Complementary and Integrative Health
• Chapter 9. Pain and Addiction
• Chapter 10. Geriatric Pain Management
• Chapter 11. Cannabis in Pain
• Chapter 12. Inpatient Pain
• Chapter 13. Pain Care Essentials: Interventional Pain
• Chapter 14. Rehabilitation in Pain Medicine
• Chapter 15. Comorbid Chronic Pain and Posttraumatic Stress Disorder: Current Knowledge, Treatments, and Future Directions
• Chapter 16. Opioids in Pain
• Chapter 17. Regenerative Medicine
• Chapter 18. Future Research in Pain
• Index