Pain
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Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate that diarrhea-predominant IBS (D-IBS) patients display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. ⋯ Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8 + or - 5.4) than IBS patients with normal membrane permeability and sensitivity (51.6 + or - 12.7) and controls (6.1 + or - 5.6) (p<0.001). A subset of D-IBS patients had increased intestinal membrane permeability that was associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.
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Randomized Controlled Trial
Intrathecal glycine for pain and dystonia in complex regional pain syndrome.
Since glycinergic neurotransmission plays an important inhibitory role in the processing of sensory and motor information, intrathecal glycine (ITG) administration may be a potential therapy for both pain and movement disorders in patients with complex regional pain syndrome (CRPS). Aims of the current study, which is the first report on ITG in humans, were to evaluate its safety and efficacy. ITG treatment during 4 weeks was studied in CRPS patients with dystonia in the period before they received intrathecal baclofen treatment. ⋯ Although there was a trend to worsening on the CGI and PGI during ITG treatment, there were no significant differences between ITG and placebo treatment in any of the outcomes. ITG given over 4 weeks was ineffective for pain or dystonia in CRPS. Although no serious adverse events occurred, further studies are required to rule out potential neurotoxicity of ITG.
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Experimental determination of pain sensitivity has received increasing attention because of emerging clinical applications (including prediction of postoperative pain and treatment response) and scientific implications (e.g. it has been proposed that above-average pain sensitivity is a risk factor for the development of chronic pain disorders). However, the use of experimental pain sensitivity assessment on a broad scale is hampered by its requirements on time, equipment and human resources and the fact that it is painful for the tested subject. Alternatives to experimental pain testing are currently lacking. ⋯ PSQ scores were significantly correlated to experimental pain intensity ratings (r = 0.56, p < 0.001) but not to pain thresholds (r = 0.03). Prediction of experimental pain intensity ratings by the PSQ was better than by pain-associated psychological factors (pain catastrophizing, depression, anxiety). This shows that the PSQ may be a simple alternative to experimental pain intensity rating procedures in healthy subjects and makes the PSQ a highly promising tool for clinical and experimental pain research.
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Adrenomedullin (AM), a member of calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pronociceptive mediator [28]. This study was undertaken to investigate the role of AM in a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Injection of CFA, but not of saline, in the unilateral hindpaw produced an increase in the expression of AM-like immunoreactivity (AM-IR) in laminae I-II of the spinal cord as well as in small- and medium-sized dorsal root ganglion (DRG) neurons at 48 h. ⋯ Furthermore, blockade of AM receptors abolished CFA-induced changes in the expression and content of CGRP-like immunoreactivity in these regions. Taken together, our results suggest that the upregulation of AM in DRG neurons contributes to the development of inflammatory pain, and this effect is mediated, at least in part, by enhancing the expression and release of CGRP. Blocking AM receptor downstream signaling effects using antagonists has the potential of relieving pain following the induction of inflammation.
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Randomized Controlled Trial
Reduction of allodynia in patients with complex regional pain syndrome: A double-blind placebo-controlled trial of topical ketamine.
A double-blind placebo-controlled crossover trial was used to determine the effects of topical ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on the sensory disturbances in 20 patients with complex regional pain syndrome (CRPS). On two occasions separated by at least one week, sensory tests to light touch, pressure, punctate stimulation, light brushing and thermal stimuli were performed in the symptomatic and contralateral limb and on each side of the forehead before and 30min after 10% ketamine cream was applied to the symptomatic or healthy limb. Venous blood for the plasma estimations of ketamine and norketamine was obtained 1h after application of the creams. ⋯ Allodynia and hyperalgesia were detected in the ipsilateral forehead to a range of stimuli (brushing, pressure, punctate stimulation, cold, heat, and warmth). In several patients, ketamine treatment of the symptomatic limb inhibited allodynia to brushing the ipsilateral forehead, suggesting that the mechanism that mediates allodynia in the symptomatic limb contributed to allodynia at more remote sites. The present study shows promise for the use of topical ketamine as opposed to parenteral and oral forms which often result in undesirable side effects.