Pain
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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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Numerous studies have found evidence for the role of catastrophizing about pain in adjustment to pain in both adults and children. However, the social context influencing pain and pain behaviour has been largely ignored. Especially in understanding the complexities of childhood pain, family processes may be of major importance. ⋯ An oblique three-factor structure emerged to best fit the data in both a sample of parents of schoolchildren (N=205) and in a sample of parents of children with chronic pain (N=107). Moreover, this three-factor structure was found to be invariant across both parent samples. Further, in the clinical sample, parents' catastrophic thinking about their child's pain had a significant contribution in explaining (a) childhood illness-related parenting stress, parental depression and anxiety, and (b) the child's disability and school attendance, beyond the child's pain intensity.
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Accumulating evidence has demonstrated that tumor necrosis factor-alpha (TNF-alpha) plays an important role in neuropathic pain. Recently, it has been shown that Lumbar 5 ventral root transection (L5 VRT) induces persistent mechanical allodynia and thermal hyperalgesia in bilateral hind paws. In the present study, the role of TNF-alpha in the L5 VRT model was investigated. ⋯ Intraperitoneal injection of thalidomide, an inhibitor of TNF-alpha synthesis, started at 2h before surgery, blocked mechanical allodynia and thermal hyperalgesia. However, the drug failed to reverse the abnormal pain behaviors, when it was applied at day 7 after surgery. These data suggest that the upregulation of TNF-alpha and TNFR1 in DRG and spinal dorsal horn is essential for the initiation but not for maintenance of the neuropathic pain induced by L5 VRT.
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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.