Pain
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Comparative Study
Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis.
Patients with mild chronic inflammation of the rectum or ileum have reduced perceptual responses to rectosigmoid distension compared to patients with irritable bowel syndrome (IBS). The current study sought to identify differences in regional cerebral blood flow (rCBF) during rectal distension, which might correspond to these perceptual differences. In 8 male ulcerative colitis (UC) patients with quiescent disease, 7 male IBS patients and 7 healthy male controls, rCBF was assessed using 15O-water positron emission tomography at baseline and during actual and anticipated but undelivered rectal distensions. ⋯ According to the connectivity analysis, this effect was mediated by inhibition of medial frontal cortex by the RLFC. Chronic colonic inflammation is not necessarily associated with increased visceral afferent input to the brain during rectal distension. In the sample studied, the primary difference between functional and quiescent inflammatory disease of the colon was in terms of greater activation of limbic/paralimbic circuits in IBS, and inhibition of these circuits in UC and controls by the RLFC.
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The alpha2A and alpha2C adrenergic receptor (AR) subtypes mediate antinociception when activated by the endogenous ligand norepinephrine. These receptors also produce antinociceptive synergy when activated concurrently with opioid receptor activation. The involvement of the opioid receptors in the mechanisms governing transcutaneous electrical nerve stimulation (TENS) has been well described. ⋯ The alpha2 adrenergic receptor selective antagonist, SK&F 86466, reversed TENS-mediated antihyperalgesia when delivered intra-articularly, but not when delivered intrathecally or intracerebroventricularly. These data suggest that peripheral alpha2 ARs contribute, in part, to TENS antihyperalgesia. This pharmacodynamic response is consistent with previous anatomical observations that alpha2A ARs are expressed on primary afferent neurons and macrophages near injured tissue.
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Comparative Study
The ontogeny of neuropathic pain: postnatal onset of mechanical allodynia in rat spared nerve injury (SNI) and chronic constriction injury (CCI) models.
Neuropathic pain is known to occur in children but remains poorly understood and treated. The aim here was to establish a model of neuropathic pain in neonatal and young rodents. In the adult the spared nerve injury (SNI) model produced robust mechanical allodynia measured as a fall in cutaneous sensory threshold to 16% of controls, within one postoperative day and lasting at least 28 days. ⋯ A similar lack of neuropathic pain behaviour in younger animals was observed using the chronic constriction injury (CCI) model, which produced a clear allodynia in adult rats but no change in hindpaw sensitivity when performed at 10 days of age. Mechanical allodynia can be evoked in very young animals with inflammatory pain, so this developmental profile is selective for peripheral neuropathic pain and suggests a remarkable ability in young animals to compensate for the sensory consequences of nerve injury. The results are consistent with human neonatal responses to nerve injury; further study of underlying mechanisms are likely to yield important information about the pathogenesis and treatment of neuropathic pain.
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Little is known about how other than cancer pain related issues are represented in medical education. A standardised questionnaire was mailed to all medical students who graduated from the five Finnish medical schools in 2001. A total of 387 students received the questionnaire and 41% responded. ⋯ The clinical problems were excellently solved. In conclusion, the IASP curriculum is well covered in the present programmes in the Finnish medical faculties. However, the quality and the methods of teaching still need improvement.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens.
Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). ⋯ The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.