Pain
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We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein-coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the antimigraine triptans, which act at 5-HT1B/D Gi-GPCRs, have been implicated in pain chronification. We determined whether sumatriptan, a prototypical 5-HT1B/D agonist, produces type II priming. ⋯ The prolongation of PGE2 hyperalgesia induced by sumatriptan was partially prevented by coinjection of antagonists for the 5-HT1B and 5-HT1D, but not 5-HT7, serotonin receptors and completely prevented by coadministration of a combination of the 5-HT1B and 5-HT1D antagonists. Moreover, the injection of selective agonists, for 5-HT1B and 5-HT1D receptors, also induced hyperalgesic priming. Our results suggest that sumatriptan, which signals through Gi-GPCRs, induces type I hyperalgesic priming, unlike agonists at other Gi-GPCRs, which induce type II priming.
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Opioid therapy for pain is associated with an increased risk for substance use disorders. This study's purpose was to determine the association between opioid misuse propensity (Screener and Opioid Assessment for Patients in Pain-Revised) and delay discounting (DD), a behavioral process linked to substance use disorders, which quantifies the extent to which outcomes are devalued because of their delay. Participants reporting chronic pain (N = 249) answered pain and opioid use questions and then completed 4 DD tasks. ⋯ Similarly, the novel Additional Pain Choice Questionnaire assessed choices between an immediate short duration of additional pain vs a longer duration of additional pain. Discounting of both additional pain and money losses were significantly associated with high Screener and Opioid Assessment for Patients in Pain-Revised scores-indicating participants at greatest risk for opioid misuse discount future punishments rather than future rewards compared with those at low risk. Measures of DD may have promise in more accurately identifying individuals at highest risk for opioid misuse during chronic opioid therapy.
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Affective instability, conceptualized as fluctuations in mood over time, has been related to ill-health and psychopathology. In this study, we examined the role of affective instability on daily pain outcomes in 70 patients with chronic pain (Mage = 49.7 years; 46 females) using an end-of-day diary. During a baseline phase, patients completed self-reported questionnaires of pain severity, pain duration, disability, depression, and anxiety. ⋯ Positive affect instability, however, showed to be unrelated to all outcomes. Current findings extend previous results and reveal the putative role of affective instability on pain-related outcomes and may yield important clinical implications. Indeed, they suggest that targeting NA instability by improving emotion regulation skills may be a strategy to diminish disability and cognitive complaints in patients with chronic pain.
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The painDETECT Questionnaire (PDQ) is commonly used as a screening tool to discriminate between neuropathic pain (NP) and nociceptive pain, based on the self-report of symptoms, including pain qualities, numbness, and pain to touch, cold, or heat. However, there are minimal data about whether the PDQ is differentially sensitive to different sensory phenotypes in NP. The aim of the study was to analyze whether the overall PDQ score or its items reflect phenotypes of sensory loss in NP as determined by quantitative sensory testing. ⋯ Patients with loss of thermal sensation (2 and 4) significantly more often reported pain evoked by light touch, and patients with loss of mechanical sensation (3 and 4) significantly more often reported numbness and significantly less often burning sensations and pain evoked by light touch. Although the PDQ was not designed to assess sensory loss, single items reflect thermal and/or mechanical sensory loss at group level, but because of substantial variability, the PDQ does not allow for individual allocation of patients into sensory profiles. It will be useful to develop screening tools according to the current definition of NP.
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T-type Ca channels (T channels), particularly Cav3.2 among the 3 isoforms, play a role in neuropathic and visceral pain. We thus characterized the effects of RQ-00311651 (RQ), a novel T-channel blocker, in HEK293 cells transfected with human Cav3.1 or Cav3.2 by electrophysiological and fluorescent Ca signaling assays, and also evaluated the antiallodynic/antihyperalgesic activity of RQ in somatic, visceral, and neuropathic pain models in rodents. RQ-00311651 strongly suppressed T currents when tested at holding potentials of -65 ∼ -60 mV, but not -80 mV, in the Cav3.1- or Cav3.2-expressing cells. ⋯ The analgesic and antihyperalgesic/antiallodynic doses of oral and i.p. RQ did not significantly affect the locomotor activity and motor coordination. Together, RQ is considered a state-dependent blocker of Cav3.1/Cav3.2 T channels and may serve as an orally available analgesic for treatment of neuropathic and inflammatory pain including distinct visceral pain with minimum central side effects.