Pain
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Randomized Controlled Trial
Can placebo and nocebo effects generalize within pain modalities and across somatosensory sensations?
Pain and other somatosensory sensations, such as itch, can be effectively decreased by placebo effects and increased by nocebo effects. There are indications that placebo effects on pain generalize to other sensations and that nocebo effects generalize within itch modalities. However, it has not yet been investigated whether learned effects can generalize within pain stimulus modalities or from pain to itch. ⋯ Results showed altered levels of heat and pressure pain with the conditioned cue in both placebo and nocebo groups in the expected directions, but no significant difference in itch in both groups. In conclusion, placebo and nocebo effects on pain may generalize within but not across stimulus modalities. This study provides a novel perspective on the role that response generalization plays in physical symptoms.
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Chronic pain affects 1 in 5 persons and contributes substantially to the global burden of disease. The 11th Revision of the International Classification of Diseases (ICD-11) includes a comprehensive classification of chronic pain. The aim of this ecological implementation field study was to evaluate the classification's interrater reliability and clinical utility in countries with different income levels. ⋯ The study showed the high interrater reliability of the new chronic pain diagnoses. The perceived clinical utility of the diagnoses indicates their superiority or equality compared with the classification systems currently used in pain clinics. These results suggest the global applicability of the classification in specialized pain treatment settings.
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Acute injury-induced pain can transition to chronic nociplastic pain, which predominantly affects women. To facilitate studies on the underlying mechanisms of nociplastic pain, we developed a mouse model in which postinjury thermal stimulation (intermittent 40°C water immersion for 10 minutes at 2 hours postcapsaicin) prolongs capsaicin (ie, experimental injury)-induced transient mechanical hypersensitivity outside of the injury area. Although capsaicin injection alone induced mechanical and thermal hypersensitivity that resolved in ∼7 days (slower recovery in females), the postinjury stimulation prolonged capsaicin-induced mechanical, but not thermal, hypersensitivity up to 3 weeks in both sexes. ⋯ Although morphine and gabapentin effectively alleviated this persistent mechanical hypersensitivity in both sexes, sexually dimorphic mechanisms mediated the hypersensitivity. Specifically, ongoing afferent activity at the previously capsaicin-injected area was critical in females, whereas activated spinal microglia were crucial in males. These results demonstrate that postinjury stimulation of the injured area can trigger the transition from transient pain to nociplastic pain more readily in females, and sex-dependent mechanisms maintain the nociplastic pain state.
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Chronic pain is often accompanied by anxiety and depression disorders. Amygdala nuclei play important roles in emotional responses, fear, depression, anxiety, and pain modulation. The exact mechanism of how amygdala neurons are involved in pain and anxiety is not completely understood. ⋯ Optogenetic activation of SOM+ neurons slightly reduced the mechanical hyperalgesia in the pain model but did not change the mechanical sensitivity in naïve mice. Instead, it induced anxiety-like behavior. Our results suggest that the PKCδ+ and SOM+ neurons in the central amygdala exert different functions in regulating pain-like and anxiety-like behaviors in mice.
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Exercise is the most common treatment recommended by healthcare providers for the treatment of musculoskeletal pain. We examined whether voluntary running wheel exercise improves pain and bone remodeling in rats with monosodium iodoacetate-induced unilateral knee joint pain. During acquisition of wheel running before osteoarthritis (OA) treatment, rats separated into 2 groups characterized by either high or low levels of voluntary wheel running as indicated by distance and peak speed. ⋯ The data suggest that similar to clinical observation, bone remodeling does not correlate with pain. In addition, these results suggest that higher intensity exercise may relieve persistent ongoing OA pain while maintaining movement-evoked nociception. The relief of ongoing pain can potentially offer significant improvement in quality of life, whereas preservation of responses to movement-evoked pain may be especially important in protecting the joint from damage because of overuse.