Pain
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This paper develops a prognostic approach to defining chronic back pain. Possible and probable chronic back pain were defined, respectively, by a 50% and an 80% (or greater) probability of future clinically significant back pain. We assessed whether an empirically derived chronic pain classification satisfied these validating criteria among 1213 primary care back pain patients assessed at baseline and at 1, 2 and 5 year follow-ups. ⋯ At baseline and 1 year, 6.1 and 4.4% of study patients met or exceeded the 80% risk threshold for probable chronic back pain. An additional 20.3% at baseline and 12.5% at 1 year met or exceeded the 50% risk threshold for possible chronic back pain. Defining chronic pain prospectively, by risk thresholds for future clinically significant pain, provides an empirically grounded approach to chronic pain assessment.
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Comparative Study
GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation.
Gangliosides are a family of sialic acid-containing glycosphingolipids that are highly enriched in the mammalian nervous system. In particular, b- and c-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to play important roles in adhesion, toxin-binding, neurite extension, cell growth and apoptosis. However, the neurobiological functions of these series of gangliosides remain largely unknown. ⋯ No significant differences in the conduction velocity of the sciatic nerve, and no apparent morphologic differences in the spinal cord and the sciatic nerve were detected between the wild-type and the mutant mice. These results suggested that b- and c-series gangliosides are critical in the development and/or maintenance of the sensory nervous system responsible for the transmission of acute pain sensation and pain modulation. Moreover, they play an important role in the development of hyperalgesia induced by inflammation.
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Comparative Study
Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice.
Capsaicin-sensitive, TRPV1 (transient receptor potential vanilloid 1) receptor-expressing primary sensory neurons exert local and systemic efferent effects besides the classical afferent function. The TRPV1 receptor is considered a molecular integrator of various physico-chemical noxious stimuli. In the present study its role was analysed in acute nociceptive tests and chronic neuropathy models by comparison of wild-type (WT) and TRPV1 knockout (KO) mice. ⋯ Chronic mechanical hyperalgesia evoked by streptozotocin-induced diabetic and cisplatin-evoked toxic polyneuropathy occurred earlier and were greater in the TRPV1 KO group. In both polyneuropathy models, at time points when maximal difference in mechanical hyperalgesia between the two groups was measured, plasma somatostatin concentrations determined by radioimmunoassay significantly increased in WT but not in TRPV1 KO mice. It is concluded that sensitization/activation of the TRPV1 receptor plays a pronociceptive role in certain models of acute tissue injury but under chronic polyneuropathic conditions it can initiate antinociceptive counter-regulatory mechanisms possibly mediated by somatostatin released from sensory neurons.
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Comparative Study
Activated PKA and PKC, but not CaMKIIalpha, are required for AMPA/Kainate-mediated pain behavior in the thermal stimulus model.
Secondary mechanical allodynia resulting from a thermal stimulus (52.5 degrees C for 45s) is blocked by intrathecal (i.t.) pretreatment with calcium-permeable AMPA/KA receptor antagonists, but not NMDA receptor antagonists. Spinal sensitization is presumed to underlie thermal stimulus-evoked secondary mechanical allodynia. We investigated whether this spinal sensitization involves activation and phosphorylation of calcium-dependent protein kinases (PKA, PKC and CaMKIIalpha), and examined if the noxious stimulus increases phosphorylated AMPA GLUR1 (pGLUR1 Ser-845 and pGLUR1 Ser-831). ⋯ Although thermal stimulation did not change either pGLUR1 Ser-845 or pGLUR1 Ser-831, it was associated with an increase in cytosolic total GLUR1. Pretreatment with a selective calcium-permeable AMPA/KA receptor antagonist (5nmol joro spider toxin), but not an NMDA receptor antagonist (25nmol d-2-amino-5-phosphonovalerate, AP-5), blocked thermal stimulus-evoked increases in phosphorylated PKA and PKC, in addition to increased cytosolic GLUR1. These findings indicate that spinal sensitization in the thermal stimulus model does not involve CaMKIIalpha activation or AMPA GLUR1 receptor phosphorylation, and differs from that occurring in NMDAr-dependent pain states.
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Randomized Controlled Trial Multicenter Study Comparative Study
Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute migraine attacks: a double-blind, placebo-controlled parallel group multicenter study.
The efficacy of intravenous acetaminophen (1000mg) in the treatment of acute migraine attacks as an alternative to parenteral application of lysine acetylsalicylate or triptans was investigated, using a multi-center, randomized, double-blind, placebo controlled study design. Migraine diagnosis was made according to the International Headache Society Classification. Sixty patients were included in three headache outpatient centers (Neurology Departments of the Universities of Regensburg, Münster and München). ⋯ Out of these, 3 patients in the acetaminophen and 4 patients in the placebo group were painfree. After 24hours 86% of the patients reported pain relief: 24 treated with acetaminophen and 27 treated with placebo. The results indicate, that 1000mg intravenous acetaminophen is not superior to placebo in treating severe acute migraine attacks.