The journal of pain : official journal of the American Pain Society
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This study investigated the relationship between neighborhood disadvantage, measured by the Area Deprivation Index (ADI), and pain-related variables in a pain psychology clinic. We also examined the sequential mediating roles of pain catastrophizing and pain-related fear on these relationships. Participants (N = 509) completed questionnaires assessing usual pain intensity, fatigue, emotional distress, and interference with daily activities. ⋯ These findings underscore that neighborhood disadvantage is associated with worse pain-related experiences and highlight the importance of considering neighborhood factors in chronic pain management. PERSPECTIVE: This study identifies potential pathways linking neighborhood disadvantage to chronic pain variables, highlighting the roles of pain catastrophizing and pain-related fear. The findings underscore the need for a holistic approach to pain management that recognizes both individual cognitive-emotional factors and the broader social context in which pain occurs.
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Sickle cell disease (SCD) is an inherited hemolytic disorder accompanied by chronic pain and recurrent acute painful episodes known as vaso-occlusive crises (VOCs). Increased Glx (glutamate+glutamine) and lowered GABA concentration have been reported in the insula of patients with fibromyalgia, a nociplastic chronic pain condition, and may affect the pathophysiology of pain-related syndromes. Therefore, proton magnetic resonance spectroscopy (1H-MRS) was conducted to measure levels of Glx and other brain metabolites using a single voxel (size: 2×3×3 cm3) in the right posterior insula cortex (PIC) in 17 individuals with SCD and 17 ethnicity-, age- and sex-matched healthy controls (HCs). ⋯ These results suggest that elevated excitatory neurotransmission in the insula might contribute to nociplastic pain in SCD. PERSPECTIVE: Our work highlighted the innovative finding of elevated levels of the excitatory neurotransmitter glutamate with glutamine in patients with SCD compared to healthy controls. The positive relationship between Glx/tCr and the frequency of VOCs suggests that an excitatory brain neurotransmitter imbalance may be involved in VOCs.
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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.
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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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Chemotherapy-induced peripheral neuropathy (CIPN) is a type of peripheral neuropathy that develops in patients treated with certain anticancer drugs. Oxaliplatin (OXA) causes CIPN in approximately 80-90 % of patients; thus, it is necessary to elucidate its underlying mechanism and develop effective treatments and prevention methods. The purpose of this study was to determine whether the pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor system in the spinal dorsal horn is involved in OXA-induced acute cold allodynia and examine the effect of a PAC1 receptor antagonist. ⋯ PERSPECTIVE: Cold allodynia is a hallmark of OXA-induced peripheral neuropathy. This study demonstrated the involvement of spinal PACAP/PAC1 receptors in OXA-induced acute cold allodynia. We propose PAC1 receptor inhibition as a new strategy for the treatment and prevention of OXA-induced acute cold allodynia.