The journal of pain : official journal of the American Pain Society
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Tolerance to the antinociceptive effect of mu-opioid receptor agonists, such as morphine and fentanyl, greatly limits their effectiveness for long-term use to treat pain. Clinical studies have shown that combination therapy and opioid rotation can be used to enhance opioid-induced antinociception once tolerance has developed. The mechanism and brain regions involved in these processes are unknown. ⋯ This finding is consistent with the functionally selective signaling that has been reported for antinociception and tolerance after morphine and fentanyl binding to the mu-opioid receptor. This research supports the notion that combination therapy and opioid rotation may be useful clinical practices to decrease opioid tolerance and other side effects. PERSPECTIVE: This preclinical study shows that there is a decrease in cross-tolerance between morphine and fentanyl within the periaqueductal gray, which is a key brain region in opioid antinociception and tolerance.
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Review Meta Analysis
Reward for pain. Hyperalgesia and allodynia induced by operant conditioning: systematic review and meta-analysis.
Learning processes have been discussed in the context of pain chronicity for decades. Particularly, operant conditioning has been used to experimentally induce and modulate pain in healthy humans. In this systematic review and meta-analysis, research findings on pain facilitation (hyperalgesic effect) and pain elicitation (allodynic effect) are evaluated. ⋯ PERSPECTIVE: Operant conditioning can be a mechanism of pain chronicity. All experimental studies investigating this hypothesis have been identified and summarized. It has been demonstrated that allodynic and hyperalgesic effects can be induced by operant conditioning.
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Policies that address opioid dose limits may help to decrease high-risk opioid prescribing. We evaluated 3 sequential and progressive decreases in high-dose (HD) opioid limits implemented by Massachusetts Medicaid over 15 years. The study population included members ages 18 to 64 years with ≥1 claim for a schedule II opioid between January 2002 and March 2017. ⋯ The natural log of the AD_MED decreased among members after implementation of 3 sequential and progressive HD prior authorization limits, as did the percentage of members exceeding each of the HD limits. PERSPECTIVE: This study demonstrates the longitudinal impact of a prior authorization policy-based HD limit in a Medicaid population. This study contributes to options for policymakers and other Medicaid programs as a potential strategy to assist in addressing the opioid epidemic.
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Spatial integration of parts of the body is impaired in patients with complex regional pain syndrome (CRPS). Because the training of mental rotation (MR) has been shown to be among the effective therapy strategies for CRPS, impairment of MR is also important for the pathophysiological understanding of CRPS. The aim of this study was to evaluate whether differences in the neural representation of MR occur between patients with CRPS and healthy controls (HC). ⋯ Regression analysis for the CRPS group emphasized the importance of putamen and nucleus accumbens activation for MR performance. This study highlights the reduced access of patients with CRPS for mental resources modulating arousal, emotional response, and subcortical sensorimotor integration. PERSPECTIVE: This study localized the underlying neural responses for impaired mental rotation in patients with complex regional pain syndrome as a decrease in basal ganglia (putamen) and nucleus accumbens activation.
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Adverse life experiences (ALEs) are associated with hyperalgesia and chronic pain, but the underlying mechanisms are poorly understood. One potential mechanism is hyperexcitability of spinal neurons (ie, central sensitization). Given that Native Americans (NAs) are more likely to have ALEs and to have a higher prevalence of chronic pain, the relationship between ALEs and spinal hyperexcitability might contribute to their pain risk. ⋯ Although relationships between ALEs and the nociceptive flexion reflex/pain were not stronger in NAs, given prior evidence that NAs experience more ALEs, this factor might contribute to the higher prevalence of chronic pain in NAs. PERSPECTIVE: This study found a dose-dependent relationship between ALEs and spinal neuron excitability. Although the relationship was not stronger in NAs than non-Hispanic whites, given prior evidence that NAs experience more ALEs, this could contribute to the higher prevalence of chronic pain in NAs.