The journal of pain : official journal of the American Pain Society
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The concomitant epidemics of chronic pain and opioid misuse in the United States have led to a call for novel analgesics with limited abuse potential. Previously, we have shown that co-delivery of a novel combination targeting both μ- and δ-opioid receptors in the peripheral and central nervous systems can produce synergistic analgesia. Loperamide, a peripherally restricted μ-opioid agonist, and oxymorphindole, a δ-opioid receptor partial agonist, synergize in multiple mouse models of hyperalgesia. ⋯ From these data we conclude that the combination of oxymorphindole and loperamide or the combination of N-benzyl-oxymorphindole and loperamide reverse incisional hyperalgesia, likely by acting in the periphery, in a large animal model without adverse effects on respiration or heart rate. PERSPECTIVE: This article presents novel opioid combinations, the μ-opioid agonist loperamide with a δ-opioid agonist, either oxymorphindole (OMI) or N-benzyl-oxymorphindole (BOMI), that relieve pain in mice and pigs without adverse side effects. These therapies could help clinicians manage pain in patients while reducing overall opioid burden and limiting side effects.
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The study of orofacial neuropathic pain necessitates the use of innovative assessment techniques, such as the facial expression of pain, which mirrors the internal state of the animals and could be utilized to identify the neural correlations involved. The Anterior Cingulate Cortex (ACC) is a crucial center in the processing of sensory and affective components of acute and neuropathic pain. However, its role in the facial response to pain remains a mystery. ⋯ Our study underscores the significant role of ACC in the development of signs of orofacial neuropathic pain, such as exacerbated facial response to mechanical stimuli. PERSPECTIVE: This article presents evidence on the sensory coding of mechanical stimulation in a neuropathic pain model in the Anterior Cingulate Cortex, using facial expression as a manifestation of the internal painful state. This evaluation provides a novel approach to evaluating the well-being of animals with neuropathic pain.
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Untreated or undertreated pain is well established as a significant problem, but unidentified pain is a distinct construct that still needs to be clearly modeled or fully described. This paper aims to develop a conceptual model of unidentified pain in humans with the goal of future development of an unidentified pain risk tool. A multi-phase process was employed consisting sequentially of 1) brainstorming followed by consensus building, 2) peer-review and publication of an integrative theoretical review protocol for "unidentified pain," 3) conduct of the integrative review, and 4) a repeated brainstorming session to identify areas of risk for unidentified pain to produce a conceptual model. ⋯ The development of this conceptual model will be used for future development and psychometric testing of a tool to recognize the risk for unidentified pain in humans. PERSPECTIVE: This focus article describes the development a conceptual model for the concept of unidentified pain in humans. This pain may occur in individuals who experience one or more interactive and cumulative hazards: cognition/communication problems, being alone, absence of a surrogate/proxy report, or presence of known painful conditions or treatments.
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Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both. ⋯ The implications for treating pancreatic pain are great in that we can no longer focus on just the pancreas. Furthermore, new treatments designed for pain disorders in other tissues may be effective in some patient with pain syndromes from the pancreas. Further research is needed to replicate and extend these observations so that new, genetics-guided rational treatments can be developed and delivered.
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In the Thermal Grill Illusion (TGI), the spatial alternation of non-noxious warm and cool temperatures elicits burning sensations that resemble the presence of noxious stimuli. Previous research has largely relied on the use of specific temperature values (i.e., 20 °C and 40 °C) to study this phenomenon in both healthy individuals and patient populations. However, this methodology fails to account for inter-individual differences in thermal sensitivity, limiting the precision with which TGI responses can be evaluated across diverse populations. ⋯ The 2D-TGC offers a comprehensive approach to investigate the TGI across populations with altered thermal sensitivity, and can be integrated with other methods (e.g., neuroimaging) to elucidate the mechanisms responsible for perceptual illusions in the thermo-nociceptive system. PERSPECTIVE: This study reveals that the Thermal Grill Illusion can be accurately measured using psychophysical methods. The innovative Two-Dimensional Thermal Grill Calibration protocol allows for personalized temperature assessments, enhancing our understanding of thermal sensitivity variations and perceptual illusions in the thermo-nociceptive system across different populations.