Seminars in Pain Medicine最新文献

Opioid conversion in the intrathecal space has been poorly studied or defined. Clinicians providing intrathecal therapy as an option in their practice often must rely on experiential-based guidelines. Spinal drug mechanics and lipid solubility heavily influence opioid dosing and conversion decisionmaking. Some clinically based guidelines for hydrophilic drug conversions are useful, but lipophilic drug conversions are best based on starting doses.

Pain facilitation has conventionally been viewed as being created and maintained solely by neurons, whereas glia (microglia and astrocytes) were not considered to be involved. Current views of glial function include a dynamic role within the spinal cord dorsal horns to create and maintain enhanced pain. This review summarizes how spinal cord glia are now implicated in diverse exaggerated pain states by proinflammatory cytokines and other potential mediators of glia-neuron communication. Glial activation is shown to be necessary and sufficient to create pain facilitation in laboratory animals. The implications for potential clinical therapeutic treatment is discussed.

Injury to the skin results in exaggerated pain both at the site of injury as well as in surrounding undamaged tissues. In this study the general organization of the somatosensory system is briefly reviewed, and then the neural mechanisms that account for hypersensitivity after cutaneous injury are discussed. In brief, exaggerated responsiveness, or sensitization, of primary afferent fibers in the skin account for hyperalgesia at the site of injury, whereas sensitization of spinal projection neurons, in particular spinothalamic and spinomesencephalic neurons, account for hyperalgesia in undamaged tissues surrounding the injury site.

Peripheral inflammation or injury can often result in enhanced transmission of sensory input through the spinal cord dorsal horn, this is termed central sensitization. This phenomenon, which results in pain responses from uninjured tissue, is a major clinical problem. Pharmacologic treatments must address neurochemical events in the spinal cord that contribute to central sensitization and resultant pain. This study reviews injury-induced glutamate receptor activation, changes in Ca²⁺ flux, and induction of calcium-dependent second messenger cascades occurring within central nociceptive afferent terminals and spinal nociceptive neurons in an attempt to explain and predict some of the relevant clinical pharmacology.

Musculoskeletal pain is a prominent feature of a variety of disorders, resulting in diffuse, difficult-to-localize, aching pain. The quality of pain associated with injury to muscle or joint is uniquely different from that of skin. Furthermore, chronic musculoskeletal pain is common, disabling, and difficult to treat. This review focuses on changes in the central nervous system relating to kaolin and carrageenan joint inflammation, carrageenan muscle inflammation, and noninflammatory repeated intramuscular acid injections. Behavioral, pharmacological, and electrophysiological data are reviewed in the context of central sensitization in these models. Sensitization of dorsal horn neurons and the consequent secondary hyperalgesia involve activation of glutamate receptors, peptidergic receptors, and second messengers in the spinal cord, which contributes to musculoskeletal pain. Understanding the role of central sensitization in musculoskeletal pain is essential for effective treatment of these disorders. Specifically, the knowledge gained from behavioral, pharmacological, and electrophysiological data will assist healthcare practitioners in choosing the most appropriate treatment.

Spinal cord injuries (SCIs) result in a devastating loss of function below the level of the lesion in which there are variable levels of motor recovery and, in most cases, central neuropathic pain syndromes (CNPs) develop several months to years after injury. Unfortunately, the study of chronic pain after SCI has been neglected due in part to the lack of appropriate animal models, but largely due to the clinically held belief that CNP is not a real phenomenon and is psychogenic in nature, rather than based on pathophysiologic mechanisms. The purpose of this study is to present standardized terminology of pain, offer insight into animal modeling issues of CNP, provide descriptions of the current clinical therapies, and examine the pathophysiologic mechanisms that provide the substrate for CNP that will lead to innovative new therapies. This information will provide new insights for health-care professionals for better care not only of SCI patients but also many other CNP syndromes.

Tissue damage as a consequence of traumatic and inflammatory processes can, in many instances, increase pain sensitivity in areas of the body remote from the site of injury. Increased pain sensitivity in the uninjured tissue surrounding the primary site of injury is referred to as secondary hyperalgesia. In most experimental models of tissue injury, secondary hyperalgesia is characterized psychophysically as enhanced pain to mechanical, but not heat stimuli. It is generally accepted that mechanisms related to the neurophysiologic phenomenon of central sensitization correspond to the psychophysical phenomenon of hyperalgesia. The purpose of this article is to review recent human psychophysical data supporting the hypothesis that secondary mechanical hyperalgesia reflects mechanisms related to central sensitization. Novel therapeutic approaches for a number of chronic pain conditions can be expected to evolve as the central mechanisms of secondary hyperalgesia become better understood.

Humans experience both visceral pain and visceral hyperalgesia. Animal and clinical studies have documented differences in the anatomy and physiology of visceral sensory circuits as compared with somatic sensory pathways, providing mechanisms to explain some of the unique characteristics of visceral pain. Evidence further suggests that both peripheral and central sensitization increase visceral sensitivity, leading to the increased perception of pain—visceral hyperalgesia. A more thorough understanding of the mechanisms that underlie the processing of visceral stimuli will improve our ability to treat individuals suffering from acute and chronic visceral pain and hyperalgesia.