The journal of pain : official journal of the American Pain Society
-
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 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.
-
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.
-
A significant driver of pain in individuals with low back pain (LBP) is alterations to endogenous pain modulation (EPM). EPM can be measured using quantitative sensory testing (QST), however; there are inconsistencies in the way QST has been implemented across the low back pain literature. The objective of this scoping review was to summarize protocols used to assess EPM using QST (pain pressure threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM)) or exercise-induced hypoalgesia (EIH) in LBP. ⋯ PERSPECTIVE: This article presents a summary of measures used to assess EPM in LBP. The results show the wide variability of protocols used in the literature. Future research should focus on creating standardized protocols, reporting guidelines and providing more guidance for researchers in selecting appropriate tests for their research questions.
-
Representativeness is an important component of generalizability. Few studies have rigorously examined the representativeness of randomized trials or observational studies of pain or musculoskeletal conditions with regards to a wide range of factors beyond age, sex, race, and ethnicity. We conducted the first study of a pain condition that uses individual-level data to directly compare the enrolled study sample to the population from which it was drawn. ⋯ This approach can be considered as a standard method to examine the representativeness of study samples in pain research. PERSPECTIVE: This article illustrates how electronic health record data can be used to directly compare the representativeness of participants in a study of pain to the study population from which participants were selected. This approach should be considered as a standard method to examine the representativeness of study samples during reporting.
-
Classical preclinical studies show that serotonin (5-HT) injected into the rostral ventromedial medulla (RVM) produces analgesia that is blocked by 5-HT2 receptor antagonists. One key modulator of 5-HT activity is the serotonin transporter (SERT) which reduces serotonergic signaling through reuptake into the presynaptic terminal. In the activity-induced muscle pain model, females show widespread pain and increased SERT expression in the RVM whereas males show localized pain and no changes in SERT expression. ⋯ Thus, we show a sex-specific role for how testosterone modulates analgesia in mice. PERSPECTIVE: This article presents novel mechanisms testosterone's protection against muscle pain in female mice showing modulation of the serotonin system in the rostral ventromedial medulla. Understanding the relationship between testosterone and serotonin could lead to better treatment of individuals with muscle pain.