Handbook of experimental pharmacology
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Recent studies have made significant progress in the knowledge of how itch sensation is processed, especially the molecular identity of neurons involved in itch signaling, both in the dorsal root ganglion and spinal cord. Despite these advances, the organization of these neurons in dorsal spinal cord circuits and how they interact with other somatosensory modalities, such as pain or temperature, remain relatively unexplored. ⋯ Here we describe the discovery of B5-I neurons, a population of inhibitory interneurons that function to inhibit itch, and review the evidence that these neurons mediate the inhibition of itch by counter stimuli. These studies are helping to solve the long-standing question of why itch makes us scratch.
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It is evident that chronic pain can modify the excitability of central nervous system which imposes a specific challenge for the management and for the development of new analgesics. The central manifestations can be difficult to quantify using standard clinical examination procedures, but quantitative sensory testing (QST) may help to quantify the degree and extend of the central reorganization and effect of pharmacological interventions. Furthermore, QST may help in optimizing the development programs for new drugs. ⋯ As most of the drug development programs in the area of pain management have not been very successful, the pharmaceutical industry has started to utilize the complementary knowledge obtained from QST profiling. Linking patients QST profile with drug efficacy profile may provide the fundamentals for developing individualized, targeted pain management programs in the future. Linking QST-assessed pain mechanisms with treatment outcome provides new valuable information in drug development and for optimizing the management regimes for chronic pain.
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Nociceptors and neurons in the central nervous system (CNS) that receive nociceptive input show remarkable plasticity in response to injury. This plasticity is thought to underlie the development of chronic pain states. Hence, further understanding of the molecular mechanisms driving and maintaining this plasticity has the potential to lead to novel therapeutic approaches for the treatment of chronic pain states. ⋯ Moreover, we discuss how commonly utilized analgesics, such as opioids, enhance priming therefore potentially contributing to the development of persistent pain states. Finally we highlight where these priming models draw parallels to common human chronic pain conditions. Collectively, these advances in our understanding of pain plasticity reveal a variety of targets for therapeutic intervention with the potential to reverse rather than palliate chronic pain states.
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Handb Exp Pharmacol · Jan 2015
ReviewNeuraxial opioid-induced itch and its pharmacological antagonism.
Given its profound analgesic nature, neuraxial opioids are frequently used for pain management. Unfortunately, the high incident rate of itch/pruritus after spinal administration of opioid analgesics reported in postoperative and obstetric patients greatly diminishes patient satisfaction and thus the value of the analgesics. ⋯ This review discusses the mechanisms underlying neuraxial opioid-induced itch and compares pharmacological evidence in nonhuman primates with clinical findings across diverse drugs. Both nonhuman primate and human studies corroborate that mixed mu/kappa opioid partial agonists seem to be the most effective drugs in ameliorating neuraxial opioid-induced itch while retaining neuraxial opioid-induced analgesia.
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Inhibitory interneurons, which use GABA and/or glycine as their principal transmitter, have numerous roles in regulating the transmission of sensory information through the spinal dorsal horn. These roles are likely to be performed by different populations of interneurons, each with specific locations in the synaptic circuitry of the region. ⋯ Several mechanisms have been proposed for this disinhibition, including death of inhibitory interneurons, decreased transmitter release, diminished activity of these cells and reduced effectiveness of GABA and glycine as inhibitory transmitters. However, despite numerous studies on this important topic, it is still not clear which (if any) of these mechanisms contributes to neuropathic pain after nerve injury.