Pain
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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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Clinical Trial
Clinical and endocrinological changes after electro-acupuncture treatment in patients with osteoarthritis of the knee.
Neurobiological mechanisms invoking the release of endogenous opioids and depression of stress hormone release are believed to be the basis of acupuncture analgesia. This study compared plasma beta-endorphin and cortisol levels with self assessment scores of intensity of pain, before and after 10 days of electro-acupuncture treatment in patients suffering from chronic pain as a result of osteoarthritis knees. Forty patients of either sex over 40 years with primary osteoarthritis knee were recruited into a single-blinded, sham-controlled study. ⋯ Following electro-acupuncture treatment there was a significant improvement in WOMAC index and VAS (p=0.001), a significant rise in plasma beta-endorphin (p=0.001), and a significant fall in plasma cortisol (p=0.016). In conclusion electro-acupuncture resulted in an improvement in pain, stiffness and disability. Of clinical importance is that an improvement in objective measures of pain and stress/pain associated biomarkers was shown above that of a sham treatment; hence demonstrating acupuncture associated physiological changes beyond that of the placebo effects.
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A prospective controlled intervention cohort study in cancer pain patients (n=50 per group) admitted to radiation oncology wards (62 beds, 3 wards) was conducted in a 1621-bed university hospital. We investigated the effect of an intervention consisting of daily pain assessment using the numeric visual analog scale (NVAS) and pain therapy counseling to clinicians based on a computerized clinical decision support system (CDSS) to correct deviations from pain therapy guidelines. Effects on guideline adherence (primary outcome), pain relief (NVAS) at rest and during physical activity (both groups: cross-sectional assessment on day 5; intervention group: every day assessment), co-analgesic prescription, and acceptance rates of recommendations (secondary outcomes) were assessed. ⋯ From 279 recommendations issued in the intervention 85% were fully accepted by the physicians. Deviations from well-established guidelines are frequent in pain therapy. A multidisciplinary pain management increased adherence to pain management guidelines.
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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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Metabotropic glutamate (mGlu) receptors, which are present on neurons and glial cells, have been shown to play a role in neuropathic pain. The present study sought to investigate how the glial inhibitors minocycline and pentoxifylline alter the effect that chronic constriction injury (CCI) has on the expression of mGlu receptors and on their associated ligands. RT-PCR analysis revealed that seven days after CCI, the mRNA levels of glial markers C1q and GFAP, as well as those of mGlu5 and mGlu3, but not mGlu7, were elevated in the lumbar spinal cord - ipsilateral to the injury. ⋯ Preemptive and repeated intraperitoneal (i.p.) administration (16 and 1h before nerve injury and then twice daily for seven days) of minocycline (30mg/kg) and pentoxifylline (20mg/kg) prevented the injury-induced changes in the levels of mGlu3 and mGlu5 receptor mRNAs and the injury-induced changes in the protein levels of all the receptors. Repeated administration of minocycline and pentoxifylline significantly attenuated CCI-induced allodynia (von Frey test) and hyperalgesia (cold plate test) measured on day seven after injury and potentiated the antiallodynic and antihyperalgesic effects of single i.p. and intrathecal (i.t.) injections of mGlu receptor ligands: MPEP, LY379268 or AMN082. We conclude that attenuation of injury-induced glial activation can reduce glutamatergic activity, thereby contributing to regulation of pain sensation.