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Osteoarthritis and Rheumatoid Arthritis

SUMMARY An estimated 21% of American adults, including 50% of those 65 years or older, have arthritis. Of these, osteoarthritis (OA) and rheumatoid arthritis (RA) are among the most common. OA is a disease of total joint failure; it affects cartilage, bone, menisci, synovium, ligaments, and neuromuscular tissue. Approximately 20–30% of adults 45 years or older have radiographic knee OA, with a similar prevalence for hand…

Postoperative Pain and Its Management

SUMMARY Management of postoperative pain is challenging because of the complex pathophysiological sequelae of surgical trauma. The broad humeral and neuronal responses to surgery are still being studied. The diversity of pain mechanisms, patient responses, and disease states necessitates a mechanistic approach to management of postoperative pain that is based on current understanding of the peripheral and central mechanisms involved in nociceptive transmission. Preparation for postoperative…

Basic Mechanisms of Muscle Pain

SUMMARY Muscle pain is distinct from cutaneous pain and one of the most common pain complaints. Muscle nociceptors are free nerve endings that are connected to the central nervous system through thin myelinated or unmyelinated afferent fibers. Most nociceptors have no ongoing activity, possess a high mechanical threshold, and can be excited by algesic agents, including bradykinin, serotonin, adenosine triphosphate, protons, and nerve growth factor. In…

Joint Pain : Basic Mechanisms

SUMMARY In a normal joint, only intense pressure on the joint and movements exceeding the working range elicit pain. However, under pathological conditions such as joint inflammation and osteoarthritis, hypersensitivity of the nociceptive system occurs frequently and leads to pain on palpation and with movements within the working range and to pain at rest. Neuronal correlates of hypersensitivity are a reduction of the mechanical threshold in…

A Critical Appraisal of Complementary and Alternative Medicine

SUMMARY Numerous forms of complementary and alternative medicine (CAM) are used with the aim of controlling pain. Many doctors now tend to accept CAM, and all too frequently the subject is discussed uncritically. This chapter focuses on acupuncture, chiropractic treatment, massage therapy, homeopathy, and herbal medicine. In particular, it reviews the clinical evidence for or against the effectiveness of these interventions, discusses the risks associated with…

The Cognitive–Behavioral Approach to Pain Management

SUMMARY A significant percentage of individuals with persistent pain continue to experience distressing symptoms despite our increased knowledge of neurophysiology and the availability of an expanded treatment armamentarium. This set of circumstances had resulted in growing awareness of the important roles of cognitive, affective, and behavioral factors in the perception, maintenance, and exacerbation of pain, along with adaptation to distressing symptoms and subsequent disability. The cognitive–behavioral…

Spinal Cord and Brain Stimulation

SUMMARY Spinal cord stimulation (SCS), which emerged as a direct clinical application of the gate control theory, has been in use since the early 1970s. It should now be regarded as a mainstream specific treatment of certain forms of neuropathic as well as ischemic pain, but not for non-ischemic nociceptive pain. Although it is an interventional form of therapy, it carries very few serious side effects.…

Neurosurgical Approaches to the Treatment of Pain

SUMMARY The neurosurgeon is often consulted for the treatment of pain. With many patients in chronic pain, an opportunity exists to intervene and eliminate the pain in a definitive manner. Since the 1970s there have been significant changes in the neurosurgical approach to the treatment of pain. In this chapter we address the various surgical lesioning procedures performed on the supratentorial structures of the brain, as…

Analgesic Drugs in Development

SUMMARY This chapter summarizes research on new drugs being developed for the treatment of pain. It outlines the process of drug discovery and development and covers the hurdles that a new drug must surmount before it can be introduced into therapy. It includes a description of not only drugs that have been discovered intentionally as analgesics but also drugs that have initially been developed for another…

Cannabinoids

SUMMARY Even though the psychotropic and therapeutic effects of Cannabis sativa have been appreciated for millennia, elucidation of the pharmacology of its constituents is altogether more recent. The receptors through which cannabinoids (natural and synthetic compounds that interact with cannabinoid receptors) exert their effects, along with their endogenous ligands and the enzymes comprising their biosynthetic and degradation pathways, have been identified only in the last 20…

Local Anesthetic Blocks and Epidurals

SUMMARY Skill in performing peripheral and neuraxial blocks enables anesthesiologists to safely manage severe acute pain during and after surgery, pain associated with vaginal delivery, cancer pain, and some chronic pain conditions. Epidural and intrathecal catheter infusions of a local anesthetic, an opioid, and adrenaline or clonidine are extremely effective for acute pain and cancer pain but require attention to important details of the procedures, are…

Anticonvulsants: Clinical

SUMMARY Anticonvulsants target a range of different molecular mechanisms, including voltage-gated sodium channels, the α 2 δ subunits of calcium channels, SV2A, K v 7 potassium channels, and AMPA. In some cases the exact mechanism of anticonvulsant action has not yet been elucidated or may involve multiple molecular mechanisms. A key attribute of anticonvulsants is that they directly or indirectly modulate neuronal excitability. This suggests that…

Mechanism of Action of Anticonvulsants as Analgesic Drugs

SUMMARY Anticonvulsant drugs provide meaningful pain relief for many patients with chronic pain. The exact mechanisms by which they exert their beneficial effects are not always known, although the most commonly used drugs appear to work through inhibition of voltage-gated sodium and calcium channels. Many anticonvulsants, however, exhibit polypharmacology, which may aid their overall efficacy in treating both epilepsy and pain. We discuss here what is…

Antidepressant Analgesics

SUMMARY This chapter provides information on the pharmacology, guidelines, recent individual quality randomized controlled trials (RCTs), and data regarding efficacy and safety from recent systematic reviews involving antidepressants and pain. Of particular interest in these studies are the clinical meaningfulness of the results and how the drugs compare with the standard treatment of the more specific subclass of tricyclic antidepressants and other analgesics. An important concern…

Cyclooxygenase Inhibitors: Clinical Use

SUMMARY Simple analgesics such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are highly effective clinically. The introduction of cyclooxgenase-2–inhibitory NSAIDs (coxibs), selective inhibitors of cyclooxygenase-2, has resulted in large quantities of safety and efficacy data. Although there are differences in efficacy between NSAIDs and paracetamol, the efficacy of classic NSAIDs and coxibs is similar, both in single doses used to treat acute postoperative pain and in…

Cyclooxygenase Inhibitors: Basic Aspects

SUMMARY Antipyretic analgesics are among the most often used medications worldwide. Their major mechanism of action is blockade of the synthesis of prostanoids, which are lipid signaling molecules produced from arachidonic acid by two cyclooxygenases. Constitutive cyclooxygenase-1 (COX-1) and inducible COX-2 generate the prostanoid precursors prostaglandin G 2 (PGG 2 ) and PGH 2 from arachidonic acid. PGH 2 is subsequently converted into the different biologically…

Opioids: Clinical Use

SUMMARY The pain-relieving effect of opioids was acknowledged early in the history of medicine. However, their abuse potential and adverse effects have resulted in widespread “opiophobia,” a phenomenon of customary underutilization of opioids. The major barriers to appropriate opioid use are insufficient knowledge, inappropriate attitudes, and economics. Traditionally, opioids have been classified as strong and weak opioids, but a functional classification of opioids based on their…

Opioids : Basic Mechanisms

SUMMARY Morphine has become the “gold standard” analgesic to which all others are compared. It is also one of the oldest drugs known. However, it is only in the past 30 years or so that the details of how opioids act, their receptors, and their actions have become clear, and the field of opioid research has gained new impetus. Many new formulations of opioids are being…

Methods of Therapeutic Trials

SUMMARY Clinical trials for acute and chronic pain can achieve high levels of precision if they adhere to some simple rules. This chapter discusses the various ways in which pain may be studied, how trials may be designed, and how the results are analyzed. The magnitude of pain intensity or pain relief is generally measured with a numerical rating scale or visual analog scale. Studies indicate…

Spinal Pharmacology of Nociceptive Transmission

SUMMARY The activity evoked in primary afferent fibers by high-intensity stimuli or tissue injury leads to a pattern of evoked spinal activity and then spinifugal outflow, which in turn activates supraspinal linkages. This review considers the multiple transmitter systems in terms of their agonists and the respective receptors that subserve these afferent–spinal, spinal–brain stem, and brain stem–forebrain projections. A variety of local and long loop connections…