Pain
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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.
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Pain behaviors are important indicators of functioning in chronic pain; however, no self-reported pain behavior instrument has been developed for pediatric populations. The purpose of this study was to create a brief pediatric measure of patient-reported pain behaviors as part of the Patient-Reported Outcome Measurement Information System (PROMIS). A pool of 47 candidate items for this measure had been previously developed through qualitative research. ⋯ Results were used along with expert consensus and alignment with the adult PROMIS pain behavior items to arrive at an 8-item pediatric pain behavior short form, and all 47 items were retained in a calibrated item bank. Confirmatory factor analysis and correlations with validated measures of pain, pain interference, and psychosocial functioning provided support for the short form's reliability and validity. The new PROMIS pediatric pain behavior scale provides a reliable, precise, and valid measure for future research on pain behavior in school-aged children with chronic pain.