Pain
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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.
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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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Randomized Controlled Trial Clinical Trial
Analgesic efficacy of tramadol, pregabalin and ibuprofen in menthol-evoked cold hyperalgesia.
We investigated the analgesic efficacy of single doses of ibuprofen, tramadol and pregabalin in menthol-evoked cold pain in a randomized, placebo-controlled four-way cross-over study in 20 healthy volunteers. Tramadol 100mg significantly reduced menthol-evoked cold hyperalgesia. Effects of ibuprofen 600mg and pregabalin 100mg were not significant. ⋯ Minor side effects also accompanied analgesic effects of pregabalin and ibuprofen in subjects responding to these drugs, mostly fatigue, dizziness and difficulties to concentrate for pregabalin and gastric upset for ibuprofen. Five out of 18 subjects had a 50% reduction of cold hyperalgesia with tramadol, three of these additionally responded to pregabalin, and two with all three drugs. The numbers needed to treat (NNT >or= 50% for tramadol 4.5, for pregabalin 9) largely agree with the reported efficacy of tramadol and of moderate dosages of pregabalin in patients with peripheral or central neuropathic pain suggesting that menthol-evoked cold pain hypersensitivity may represent a valid model for neuropathic pain, particularly cold allodynia.
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Randomized Controlled Trial
Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study.
Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. The pathophysiology of CRPS is not known but both clinical and experimental evidence demonstrate the important of the NMDA receptor and glial activation in its induction and maintenance. Ketamine is the most potent clinically available safe NMDA antagonist that has a well established role in the treatment of acute and chronic pain. ⋯ This study showed that intravenous ketamine administered in an outpatient setting resulted in statistically significant (p<0.05) reductions in many pain parameters. It also showed that subjects in our placebo group demonstrated no treatment effect in any parameter. The results of this study warrant a larger randomized placebo controlled trial using higher doses of ketamine and a longer follow-up period.
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Randomized Controlled Trial Clinical Trial
Motor cortex electrical stimulation applied to patients with complex regional pain syndrome.
Motor cortex stimulation (MCS) is useful to treat patients with neuropathic pain syndromes, unresponsive to medical treatment. Complex regional pain syndrome (CRPS) is a segmentary disease treated successfully by spinal cord stimulation (SCS). However, CRPS often affects large body segments difficult to cover by SCS. ⋯ VAS and McGill pain scales diminished significantly (p<0.01) throughout the follow-up, accompanied by disappearance of the sensory (allodynea and hyperalgesia) and sympathetic signs. MCS is effective not only to treat pain, but also improve the sympathetic changes in CPRS. Mechanism of action is actually unclear, but seems to involve sensory input at the level of the spinal cord.