The journal of pain : official journal of the American Pain Society
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We have recently developed an animal model of fibromyalgia syndrome in the rat. In this model, rats exposed to unpredictable sound stress develop a delayed onset enhancement and prolongation of cytokine-induced mechanical hyperalgesia in muscle and skin. In this study, we tested the hypothesis that our model also manifests symptoms of common comorbid diagnoses: irritable bowel syndrome, temporomandibular disorder, and anxiety. Both visceral sensitivity and cytokine hyperalgesia in masseter muscle were present in the stressed rats. Furthermore, in an established model of irritable bowel syndrome-water avoidance-we observed significant muscle hyperalgesia. Finally, using the elevated plus maze to assess for anxiety level, we observed a significantly higher anxiety level in sound stress-exposed rats. Thus, unpredictable sound stress produces a condition in the rat with several features-delayed onset visceral and temporomandibular hyperalgesia and increased anxiety, as well as cutaneous and muscle hyperalgesia-commonly found in patients with fibromyalgia syndrome. ⋯ A stress model-unpredictable sound-in the rat exhibits several features (cutaneous, musculoskeletal, and visceral hyperalgesia, as well as anxiety) that are found in patients with fibromyalgia syndrome. Thus, this model may be used to test hypotheses about the underlying mechanisms and response to therapy in patients with fibromyalgia.
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Cold hyperalgesia is 1 of the characteristic signs in neuropathic pain. Topical application of menthol has been proposed as model to study cold hyperalgesia. The aim of this psychophysical study was to characterize the human surrogate of neuropathic pain of topical menthol application by using a standardized and validated protocol of quantitative sensory testing (QST). Additionally, we assessed the course of the signs elicited by menthol application over time. High-concentration 40% L-menthol was applied topically on hairy skin in 12 healthy subjects. Standardized psychophysical tests (QST) assessing 13 parameters including thermal and mechanical detection and pain thresholds were obtained before and every 45 minutes after menthol removal up to 4 hours after menthol application. Menthol decreased the cold pain threshold, mechanical pain threshold, and increased the mechanical pain sensitivity in all subjects displaying cold and mechanical pinprick hyperalgesia. In all subjects, an area of secondary pinprick hyperalgesia could be determined. Within the observation time, the decreased cold pain threshold increased continuously, whereas the signs of primary and secondary pinprick hyperalgesia remained stable. The data suggest that topical 40% menthol application is a useful model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. ⋯ This study establishes the topical application of high-concentration 40% menthol as a useful stable model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. The provided long-term data are important for psychophysical and pharmacological research in humans and provide us with insights on experimental cold and mechanical hyperalgesia.
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We defined the nature of the pharmacological interaction between ginsenosides and morphine in a nociceptive state and clarified the role of the different types of opioid receptor in the effects of ginsenosides. An intrathecal catheter was placed in male Sprague-Dawley rats. Pain was induced by formalin injection into the hindpaw. Isobolographic analysis was used to evaluate drug interactions. Furthermore, a nonselective opioid receptor antagonist (naloxone), a μ opioid receptor antagonist (CTOP), a δ opioid receptor antagonist (naltrindole), and a κ opioid receptor antagonist (GNTI) were given intrathecally to verify the involvement of the opioid receptors in the antinociceptive effects of ginsenosides. Both ginsenosides and morphine produced antinociceptive effects in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of the ginsenosides-morphine mix. Intrathecal CTOP, naltrindole, and GNTI reversed the antinociceptive effects of ginsenosides. RT-PCR indicated that opioid receptors' mRNA was detected in spinal cord of naïve rats and the injection of formalin had no effect on the expression of opioid receptors' mRNA. Taken together, our results indicate synergistic antinociception following intrathecal coadministration of a ginsenosides/morphine mix in the formalin test, and that μ, δ, and κ opioid receptors are involved in the antinociceptive mechanism of ginsenosides. ⋯ This article concerns the antinociceptive activity of ginsenosides, which increases antinociception by morphine. Thus, a spinal combination of ginsenosides and morphine may be useful in the management of acute pain as well as facilitated state pain.