Mol Pain
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Intraplantar administration of complete Freund's adjuvant (CFA) and formalin are two noxious stimuli commonly used to produce sustained pain-related behaviors in rodents for research on neurobiology and treatment of pain. One clinically relevant manifestation of pain is depression of behavior and mood. This study compared effects of intraplantar CFA and formalin on depression of positively reinforced operant behavior in an assay of intracranial self-stimulation (ICSS) in rats. Effects of CFA and formalin on other physiological and behavioral measures, and opioid effects on formalin-induced depression of ICSS, were also examined. ⋯ These results suggest differential efficacy of sustained pain stimuli to depress brain reward function in rats as assessed with ICSS. Formalin-induced depression of ICSS does not appear to engage brain kappa opioid systems.
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This study aimed to evaluate the prophylactic effect of goshajinkigan (GJG) on paclitaxel (PTX)-induced neuropathy and to elucidate the mechanism of action. ⋯ These results showed that PTX induced hyperalgesia by enhancing TRPV4 expression, and suggested that GJG might alleviate hyperalgesia by preventing degeneration of the ganglion cells and suppressing TRPV4 expression.
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Genetic polymorphisms, gender and age all influence the risk of developing chronic neuropathic pain following peripheral nerve injury (PNI). It is known that there are significant inter-strain differences in pain hypersensitivity in strains of mice after PNI. In response to PNI, one of the earliest events is thought to be the disruption of the blood-spinal cord barrier (BSCB). The study of BSCB integrity after PNI may lead to a better understanding of the mechanisms that contribute to chronic pain. ⋯ DCE-MRI provides a sensitive and non-invasive method to follow BSCB permeability in the same group of mice over time. Examining differences between mouse strains, we demonstrated that there is an important genetically-based control of the PNI-induced increase in BSCB permeability and that the critical genetic determinants of BSCB opening after PNI are distinct from those that determine genetic variability in PNI-induced pain hypersensitivity.
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The long term use of opioids for the treatment of pain leads to a group of maladaptations which includes opioid-induced hyperalgesia (OIH). OIH typically resolves within few days after cessation of morphine treatment in mice but is prolonged for weeks if histone deacetylase (HDAC) activity is inhibited during opioid treatment. The present work seeks to identify gene targets supporting the epigenetic effects responsible for OIH prolongation. ⋯ The present study identified two genes whose expression is regulated by epigenetic mechanisms during morphine exposure. Treatments aimed at preventing the acetylation of histones or blocking BDNF and dynorphin signaling may reduce OIH and improve long-term pain using opioids.
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Lumbar radicular pain is categorized as a type of neuropathic pain, but its pathophysiological mechanisms are not fully understood. The substantia gelatinosa (SG) in the spinal cord dorsal horn receives primary afferent inputs and is considered to be a therapeutic target for treating neuropathic pain. In vivo patch-clamp recording is a useful procedure for analyzing the functional properties of synaptic transmission in SG neurons. Transient receptor potential ankyrin 1 (TRPA1) has been widely identified in the central and peripheral nervous systems, such as in the peripheral nociceptor, dorsal root ganglion, and spinal cord dorsal horn and is involved in synaptic transmission of pain. However, its functional role and mechanism of pain transmission in the spinal cord dorsal horn are not well understood. The purpose of this study was to use in vivo patch-clamp analysis to examine changes in the excitatory synaptic transmission of SG neurons treated with TRPA1 antagonist and to clarify the potential role of TRPA1 in the rat spinal cord dorsal horn. ⋯ These data showed that the TRPA1 antagonist had an inhibitory effect on mechanical hypersensitivity and hyperalgesia as well as on physiological pain transmission in the spinal cord dorsal horn. This suggests that TRPA1 is consistently involved in excitatory synaptic transmission even in the physiological state and has a role in coordinating pain transmission.