Articles: hyperalgesia.
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Rapid and effective treatment of cancer-induced bone pain remains a clinical challenge and patients with bone metastasis are more likely to experience severe pain. The voltage-gated sodium channel Nav1.8 plays a critical role in many aspects of nociceptor function. Therefore, we characterized a rat model of cancer pain and investigated the potential role of Nav1.8. ⋯ These findings suggest that Nav1.8 plays a role in the development and maintenance of bone cancer pain.
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Whereas acute stress often results in analgesia, chronic stress can trigger hyperalgesia/allodynia. This influence of long-term stress on nociception is relevant to numerous painful pathologies, such as fibromyalgia (FM), characterized by diffuse muscular pain (hyperalgesia) and/or tenderness (allodynia). Hence, there is a need for pre-clinical models integrating a chronic-stress dimension to the study of pain. ⋯ This stress also resulted in mechanical allodynia in the von Frey filaments model (60% decrease in threshold during week 2-5). However, such a stress regimen had no influence in the Randall-Selitto test of mechanical hyperalgesia, and in the tail immersion models of cold (4 degrees C) or hot (48 degrees C) thermal hyperalgesia, as well as cold (15 degrees C) allodynia. This model of prolonged/intermittent restraint stress may be useful in investigating the mechanisms linking stress and pain, and provide an assay to assess the potential therapeutic efficacy of drugs targeted against painful pathologies with a strong stress component, including but not restricted to FM.
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Brain research bulletin · Dec 2009
Effect of puerarin on P2X3 receptor involved in hyperalgesia after burn injury in the rat.
The study investigated the effects of puerarin on P2X(3) receptor involved in hyperalgesia after burn injury in the rat. Superficial second degree burn injury models were adopted. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured and the P2X(3) receptor expressions in dorsal root ganglion (DRG) from burn injury models rats were detected by immunohistochemistry, in situ hybridization, RT-PCR and western blot. ⋯ At day 3 post-burn, the expressions of P2X(3) protein and mRNA in DRG neurons in untreated superficial second degree back burn group were increased significantly compared with sham back burn group, puerarin-treated back unburned control group, blank back control group, while in puerarin-treated superficial second degree back burn group, the P2X(3) protein and mRNA expressions were decreased markedly. There is no significant difference in sham back burn group, puerarin-treated back unburned control group, blank back control group. Therefore, puerarin may reduce the nociceptive transmission of burn injury pain mediated by P2X(3) receptor and alleviate P2X(3) receptor involved in hyperalgesia after burn injury in the rats.
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The central processing of peripheral nociceptive messages is highly controlled by the activity of local inhibitory networks in the spinal cord and supraspinal centers. Recently, it has been shown that endogenous 3alpha-reduced neurosteroids (3alphaNS) exert a significant spinal antinociception by potentiating GABA(A) receptor function. Because endogenous 3alphaNS can be produced in many relay structures of the nociceptive system, we tested the potential analgesic efficacy of promoting the production of neurosteroids by using etifoxine (ETX, 50mg/kg i.p.). ⋯ Both the curative and preventive effects of ETX on pain symptoms were mediated by the production of 3alphaNS as demonstrated in animals treated with the enzymatic inhibitor provera (6-medroxyprogesterone acetate; 20mg/kg s.c.). Altogether, this study shows for the first time that promoting 3alphaNS could be a possible therapeutic strategy to treat neuropathic pain symptoms. Since ETX is already available as an anxiolytic, its use in humans, provided that its analgesic properties are confirmed, could be rapidly considered.
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Endometriosis is a painful disorder defined by extrauteral endometrial growths whose contribution to pain symptoms is poorly understood. Endometriosis is created in rats by autotransplanting on abdominal arteries pieces of either uterus (ENDO), which form cysts, or fat (shamENDO), which do not form cysts. ENDO, but not shamENDO induces vaginal hyperalgesia. ⋯ The increases in ENDO-induced hyperalgesia produced by the sham-cyst-removal surgery were smaller in proestrus than in other estrous stages. During the other stages (but not during proestrus), sympathetic innervation of the cysts increased. These results suggest that maintenance of ENDO-induced vaginal hyperalgesia requires continued presence of at least some ectopic endometrial tissue, and that surgical treatment that fails to remove ectopic endometrial tissue can exacerbate the hyperalgesia, possibly due in part to an increase in the cysts' sympathetic innervation.