Articles: hyperalgesia.
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The transient receptor potential vanilloid receptor type-1 (TRPV1) is critically involved in peripheral nociceptive processes of somatic and visceral pain. However, the role of the capsaicin receptor in the brain regarding visceral pain remains elusive. ⋯ Notably, intracerebral TRPV1 antagonism by SB 366791 significantly reduced chemical and inflammatory spontaneous abdominal nocifensive responses, as observed by reduced expressions of nociceptive facial grimacing, illustrating the affective component of pain. In addition to the established role of cerebral TRPV1 in anxiety, fear, or emotional stress, we demonstrate here for the first time that TRPV1 in the brain modulates visceral nociception by interfering with the affective component of abdominal pain.
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Emerging lines of evidence indicate that production of reactive oxygen species (ROS) at distinct sites of the nociceptive system contributes to the processing of neuropathic pain. However, the mechanisms underlying ROS production during neuropathic pain processing are not fully understood. We here detected the ROS-generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in macrophages of dorsal root ganglia (DRG) in mice. ⋯ Nox2-deficient mice displayed reduced neuropathic pain behavior after peripheral nerve injury, whereas their immediate responses to noxious stimuli were normal. Moreover, injury-induced upregulation of tumor necrosis factor α was absent, and activating transcription factor 3 induction was reduced in DRG of Nox2-deficient mice, suggesting an attenuated macrophage-neuron signaling. These data suggest that Nox2-dependent ROS production in macrophages recruited to DRG contributes to neuropathic pain hypersensitivity, underlining the observation that Nox-derived ROS exert specific functions during the processing of pain.
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Peripheral neuropathy is the major dose-limiting side effect of cisplatin and oxaliplatin, and there are currently no effective treatments available. The aim of this study was to assess the pharmacological mechanisms underlying chemotherapy-induced neuropathy in novel animal models based on intraplantar administration of cisplatin and oxaliplatin and to systematically evaluate the analgesic efficacy of a range of therapeutics. ⋯ This study established a novel animal model of cisplatin-induced mechanical allodynia consistent with the A-fiber neuropathy seen clinically. Systematic assessment of a range of therapeutics identified several candidates that warrant further clinical investigation.
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Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. ⋯ Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9(-/-) mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics.
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Behavioral neuroscience · Oct 2014
Spinal cord stimulation (SCS) improves decreased physical activity induced by nerve injury.
Spinal cord stimulation (SCS) is used to manage treatment of neuropathic pain to reduce pain and hyperalgesia and to improve activity. Prior studies using animal models of neuropathic pain have shown that SCS reduces hyperalgesia; however, it is unclear whether SCS affects physical activity. Therefore, we tested whether nerve injury (spared nerve injury [SNI] model) reduced physical activity levels, and whether SCS could restore these decreased activity levels. ⋯ Both 4- and 60-Hz SCS increased the overall activity (lines crossed), distance traveled, and rearing, but not grooming behaviors for 3 months. This effect remained similar across the 3 months. Thus, measurement of spontaneous physical activity could be useful to examine nocifensive behaviors after nerve injury and is sensitive to SCS.