Pain
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Comparative Study
Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy.
Selective ligation of the L5/L6 spinal nerves produces a partial denervation of the hindpaw and has proved to be a useful model for studying the mechanisms underlying neuropathic pain. Two weeks after surgery, in vivo electrophysiological studies were performed in sham operated and nerve injured rats and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical and heat) stimuli were recorded. The systemic effects of three N-methyl-D-aspartate receptor (NMDA) antagonists, ketamine (1-10 mg/kg), memantine (1-20 mg/kg) and MK-801 (0.1-5 mg/kg) were compared. ⋯ The effects of MK-801 were comparable between SNL and sham operated rats for all neuronal measures (wind-up, postdischarge, thermal and noxious mechanical evoked responses). The differential blocking abilities of these antagonists on the various neuronal responses may relate to the characteristics of their voltage-dependent blockage of the channel associated with the receptor. The favourable side effect profile of memantine supports its potential use for the treatment of neuropathic pain.
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Randomized Controlled Trial Comparative Study Clinical Trial
Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR).
Oral transmucosal fentanyl citrate (OTFC); Actiq) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients' usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen. ⋯ GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study. Somnolence, nausea, constipation, and dizziness were the most common drug-associated side effects. In conclusion, OTFC was more effective than MSIR in treating breakthrough cancer pain.
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Randomized Controlled Trial Clinical Trial
Habituation of the early pain-specific respiratory response in sustained pain.
Neurokinin-1 receptor and mu-opioid receptor agonists affect respiratory rhythm when injected directly into the preBötzinger brainstem complex, which is the hypothesized site for respiratory rhythmogenesis in mammals (Science 286 (1999) 1566). Early stress-induced analgesia (SIA) is naloxone-insensitive and as such considered independent of the activation of the mu-opioid system. Prolonged application of electrical shocks, however, produces analgesia that is mediated by the mu-opioid system (Science 208 (1980) 623). ⋯ In the early stage of pain, all monitored variables (respiration rate, minute ventilation volume, and inspiratory and expiratory flow rates) were elevated to statistically significant degrees when compared to measurements taken at baseline or during control infusion. Only respiration rate continued to be significantly elevated in sustained pain. We concluded that rhythmogenic neurons in the preBötzinger brainstem complex appear as the likely target for pro-nociceptive and anti-nociceptive input, explaining both the observed initial facilitation and subsequent habituation of respiration in early and sustained pain.
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Positron emission tomography (PET) imaging of spinal cord in monkeys with a cholinergic tracer demonstrates increased spinal cholinergic activity in response to an analgesic dose of morphine, and this PET result correlates with measurement of acetylcholine spillover into spinal cord extracellular space induced by morphine, as measured by microdialysis. Previous studies in rats, mice, and sheep demonstrate activation of spinal cholinergic neurons by systemic opioid administration, and participation of this cholinergic activity in opioid-induced analgesia. Testing the relevance of this observation in humans has been limited to measurement of acetylcholine spillover into lumbar cerebrospinal fluid. ⋯ The one animal which did not show increased spinal cholinergic activity by PET from this dose of morphine also did not show increased acetylcholine from this morphine dose in the microdialysis experiment. These data confirm the ability to use PET to image spinal cholinergic terminals in the monkey spinal cord and suggest that acute changes in cholinergic activity can be imaged with this non-invasive technique. Following preclinical screening, PET scanning with [(18)F]FBT may be useful to investigate mechanisms of analgesic action in normal humans and in those with pain.
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Recent research indicates that people who are fearful of pain tend to report more negative pain experiences. It also seems that attentional mechanisms may be particularly important in the perception of painful stimuli, especially amongst pain fearful individuals. Drawing on a paradigm used to examine biased cognitive processes in the emotional disorders, the current study investigated whether the fear of pain would be related to a greater selective attentional bias in favour of pain-related stimuli. ⋯ No group differences were found for either social threat or positive stimuli. These results indicate that one reason why those with a high fear of pain are particularly susceptible to negative pain experiences could be due to biased attentional processes. Suggestions for cognitive interventions designed to reduce such biases are discussed, as are directions for future research.