Pain
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Systemic administration of morphine induced a hyperalgesic response in the hot plate test, at an extremely low dose (1-10 microg/kg). We have examined in vivo whether morphine, at an extremely low dose, induces acute central hypernociception following activation of the opioid receptor-mediated PLC/PKC inositol-lipid signaling pathway. The PLC inhibitor U73122 and the PKC blocker, calphostin C, dose dependently prevented the thermal hypernociception induced by morphine. ⋯ When mice were treated with a morphine analgesic dose (7 mg/kg), the downregulation of PLCbeta3 or PKCgamma at the same aODN doses used for the prevention of the hyperalgesic effect induced, respectively, a 46% and 67% potentiation in analgesic response. Experimental and clinical studies suggest that opioid may activate pronociceptive systems, leading to pain hypersensitivity and short-term tolerance, a phenomenon encountered in postoperative pain management by acute opioid administration. The clinical management of pain by morphine may be revisited in light of the identification of the signaling molecules of the hyperalgesic pathway.
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Multicenter Study
Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.
The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. ⋯ Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.
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We report the development of the Pain Solutions Questionnaire (PaSol), an instrument designed to measure assimilative (efforts at changing or solving pain) and accommodative (accepting that pain cannot be solved, and changing life goals) responses to the problems associated with pain. Data were collected from 476 adults suffering from chronic pain. Exploratory and confirmatory factor analyses resulted in a 14-item instrument with an adequate oblique 4-factor structure: (1) Solving Pain scale (4 items), (2) Meaningfulness of Life Despite Pain scale (5 items), (3) Acceptance of the Insolubility of Pain scale (3 items), and (4) Belief in a Solution scale (2 items). ⋯ The Meaningfulness of Life Despite Pain scale was important in explaining disability and affective distress. The Solving Pain scale had a unique and independent contribution in explaining affective distress. Results are discussed in terms of how a persistence in assimilative coping, even though the pain problem is insoluble, may increase hypervigilance, catastrophizing, distress and disability.
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There is compelling evidence for a strong facilitatory drive modulating spinal nociceptive transmission. This is in part via serotonergic pathways and originates from the rostroventral medulla. We previously demonstrated that neuropathic pain is associated with an enhanced descending facilitatory drive onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT acting at spinal 5-HT3 receptors. ⋯ Sham-5,7DHT and sham-saline animals showed very little response sensitivity on either hindpaw. This 5-HT-mediated difference in behaviour was independent of both the up-regulation of the NK1 receptor and spinal microglial activation produced by nerve injury. These data suggest that supraspinal serotonergic influences under these conditions are facilitatory and are implicated in the maintenance of spinal cord neuronal events leading to the behavioural hypersensitivity manifested after peripheral nerve damage.