Articles: hyperalgesia.
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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.
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Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer, but it causes acute peripheral neuropathy (acral paresthesias triggered by exposure to cold) and chronic neuropathy (abnormal of sensory and motor dysfunction). Oxaliplatin is metabolized to oxalate and dichloro(1,2-diaminocyclohexane)platinum (Pt(dach)Cl(2)). Although the chelating of Ca(2+) with oxalate eliminated from oxaliplatin is thought as one of the reasons for the neuropathy, there is little behavioral evidence. ⋯ The pre-administration of calcium or magnesium (0.5mmol/kg, i.v.) before oxaliplatin or oxalate prevented the cold hyperalgesia but not mechanical allodynia. However, the treatment with calcium or magnesium after the development of neuropathy could not attenuate the cold hyperalgesia or mechanical allodynia. These findings suggest the involvement of oxalate in oxaliplatin-induced cold hyperalgesia but not mechanical allodynia, and usefulness of prophylactic treatments with calcium and magnesium on the acute peripheral neuropathy.
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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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Pain in early life can enhance the response to subsequent injury, but effects are influenced by both the nature and timing of neonatal injury. Using plantar hindpaw incision, we investigated how postnatal age influences the response to repeat surgical injury two weeks later. The degree and time course of behavioural changes in mechanical withdrawal threshold were measured, and injury-related hyperalgesia was further quantified by flexion reflex electromyographic responses to suprathreshold mechanical stimuli 24 h following incision. ⋯ Repeat peri-operative, but not a single pre-operative sciatic block, prevented the enhanced response to repeat incision two weeks later. Our results show that the first postnatal week represents a critical period when incision increases hyperalgesia following repeat surgery two weeks later, and effects are initiated by peripheral afferent activity. This has potential therapeutic implications for the type and duration of peri-operative analgesia used for neonatal surgery.
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Both pro-nociceptive and antinociceptive mediators are released in the tissues during inflammation. Balance of these two types of mediators determines the induction and maintenance of pain or hypernociception. This study was designed to explore whether 5-HT(2A) receptors in the periphery contributed to the maintenance of carrageenan-evoked hyperalgesia. ⋯ The hypoalgesia was completely abolished by local or systemic injection of naloxone methiodide. The present study suggests that 5-HT(2A) receptors were involved in the maintenance of inflammatory pain, and that 5-HT suppressed inflammation-associated endogenous opioid analgesia contributing to its pro-nociceptive actions in the periphery. It implied a possible therapeutic benefit of blockade of local 5-HT(2A) receptors in the treatment of inflammatory pain.