Pain
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This study compared a remote-delivered pain management program, the Pain Course, when delivered in online and workbook formats. Participants (n = 178) were randomised into 2 groups: (1) an Internet Group (n = 84) who were provided with secure accounts to the program in an online format; or (2) a Workbook Group (n = 94) who were mailed workbook versions of the program. The content of both programs was identical and comprised 5 core lessons, which participants were encouraged to work through over an 8-week period, according to a prescribed timetable. ⋯ Further improvements were observed in disability levels to 3-month follow-up, and improvements across the other primary outcomes were maintained until 12-month follow-up. High treatment completion rates and levels of satisfaction were reported in both groups, and both groups required a similarly small amount of clinician contact per participant (M = 74.85 minutes; SD = 41.03). These results highlight the public health potential of remote-delivered pain management programs, delivered in either workbook or online formats, as methods of increasing access to pain management.
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Thoracotomy results in chronic postoperative pain (CPTP) in half of the cases. Earlier findings in rat models of persistent post-surgical pain suggest that spinal pathways are critical for pain onset but not its maintenance. Descending systems from the brain stem modulate nociceptive transmission in the spinal cord and contribute to persistent pain, but their role in chronic postoperative pain has not been studied. ⋯ SSP-SAP given at postoperative day 10 was equally effective in ablating NK-1R neurons but fully reversed mechano-hypersensitivity in only 3 of 9 hypersensitive rats. Fewer rats showed intense pain-like behavior, by Qualitative Hyperalgesia Profile analysis, in the Prevention than in the Control conditions, and the more intense pain behaviors declined along with SSP-SAP-induced Reversal of hypersensitivity. Neurokinin-1 receptor-expressing neurons in RVM appear essential for the development but contribute only partially to the maintenance of CPTP.
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The immune and sensory systems are known for their close proximity and interaction. Indeed, in a variety of pain states, a myriad of different immune cells are activated and recruited, playing a key role in neuronal sensitisation. During inflammatory pain it is thought that mast cells (MC) are one of the immune cell types involved in this process, but so far the evidence outlining their direct effect on neuronal cells remains unclear. ⋯ We also demonstrate that NGF treatment in vitro does not lead to an increased level of tumor necrosis factor-α in bone marrow-derived MC. Furthermore, our qRT-PCR data reveal that MC express negligible levels of NGF receptors, thereby explaining the lack of response to NGF. Together, our data suggest that MC do not play a direct role in peripheral sensitisation during inflammatory conditions.
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Randomized Controlled Trial
Midazolam as an active placebo in three fentanyl-validated nociceptive pain models.
The use of inactive placebos in early translational trials of potentially analgesic compounds is discouraged because of the side-effect profiles of centrally acting analgesics. Therefore, benzodiazepines are used, although their use has not been validated in this context. Whether benzodiazepines confound the results of acute pain tests is unknown. ⋯ The findings of this study show that midazolam can be used as an active placebo in analgesic drug trials. Furthermore, the proposed models were simple to implement and very effective in detecting analgesia. The test battery can be used in translational trials for new compounds and comes with an active placebo and an optional active comparator.