Handbook of experimental pharmacology
-
Nonimmobilizing, inhalational anesthetic-like compounds are experimental agents developed as a tool to investigate the mechanism of action of general anesthetics. Clinically used for more than 150 years, general anesthesia has until now defied all attempts to formulate a theory of its mechanisms that would link, in an uninterrupted logical chain, observations on the molecular level-via effects on the cellular and network levels-to the in vivo phenomenon. Nonimmobilizers, initially termed nonanesthetics, are substances that disobey the Meyer-Overton rule. ⋯ This discovery required not only the introduction of the more precise term "nonimmobilizers," but also excluded one important component of anesthesia, i.e., amnesia, from application of the algorithm. On the other hand, compared to inhalational anesthetics, nonimmobilizers interact with relatively few molecular targets, also limiting the usefulness of the nonimmobilizer algorithm. Nevertheless, nonimmobilizers have not only yielded useful results but can, by virtue of those very properties that make them less than ideal for anesthesia research, be used as experimental tools in the neurosciences far beyond anesthetic mechanisms.
-
The discovery of the endogenous systems of analgesia has produced a large amount of research aimed at investigating their biochemical and neurophysiological mechanisms and their neuroanatomical localization. Nevertheless, the neurobiological acquisitions on these mechanisms have not been paralleled by behavioural correlates in humans--in other words, by the understanding of when and how these endogenous mechanisms of analgesia are activated. ⋯ By contrast, today the placebo analgesic effect represents one of the best-described situations in which this endogenous opioid network is naturally activated in humans. Therefore, not only is placebo research helpful towards improving clinical trial design and medical practice, but it also provides us with a better understanding of the endogenous mechanisms of analgesia.
-
Handb Exp Pharmacol · Jan 2007
ReviewLimitations of pharmacotherapy: behavioral approaches to chronic pain.
Pharmacotherapy is most appropriate in acute pain, whereas in chronic pain states behavioral approaches or a combination of behavioral treatment and pharmacotherapy is more appropriate. In this chapter we first describe the role of learning and memory as well as other psychological factors in the development of chronic pain and emphasize that chronic pain must viewed as the result of a learning process with resulting central neuroplastic changes. We then describe operant behavioral and cognitive-behavioral treatments as well as biofeedback and relaxation techniques and present innovative treatment procedures aimed at altering central pain memories. We complete the section with a discussion of combined behavioral and pharmacological approaches and an interdisciplinary view.
-
Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. This chapter, on the analgesic aspects of local anesthetics, reviews their broad actions that affect many different molecular targets and disrupt their functions in pain processing. Application of local anesthetics to peripheral nerve primarily results in the blockade of propagating action potentials, through their inhibition of voltage-gated sodium channels. ⋯ Many G protein-coupled receptors are susceptible to local anesthetics, with particular sensitivity of those coupled via the Gq alpha-subunit. Local anesthetics are also infused intravenously to yield plasma concentrations far below those that block normal action potentials, yet that are frequently effective at reversing neuropathic pain. Thus, local anesthetics modify a variety of neuronal membrane channels and receptors, leading to what is probably a synergistic mixture of analgesic mechanisms to achieve effective clinical analgesia.
-
Pain research has uncovered important neuronal mechanisms that underlie clinically relevant pain states such as inflammatory and neuropathic pain. Importantly, both the peripheral and the central nociceptive system contribute significantly to the generation of pain upon inflammation and nerve injury. Peripheral nociceptors are sensitized during inflammation, and peripheral nerve fibres develop ectopic discharges upon nerve injury or disease. ⋯ The spinal processes are significantly influenced by brain stem circuits that inhibit or facilitate spinal nociceptive processing. Numerous mechanisms are involved in peripheral and central nociceptive processes including rapid functional changes of signalling and long-term regulatory changes such as up-regulation of mediator/receptor systems. Conscious pain is generated by thalamocortical networks that produce both sensory discriminative and affective components of the pain response.