European journal of pain : EJP
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The analgesic properties and mechanisms of loperamide hydrochloride, a peripherally acting opioid receptor agonist, in neuropathic pain warrant further investigation. ⋯ These findings suggest that both systemic and local administration of loperamide induce an opioid receptor-dependent inhibition of heat and mechanical hyperalgesia in nerve-injured rats, but that local paw administration of loperamide also induces thermal and mechanical antinociception.
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Randomized Controlled Trial
Sex differences in analgesic response to ibuprofen are influenced by expectancy: a randomized, crossover, balanced placebo-designed study.
To determine whether there is a sex difference in placebo and ibuprofen analgesia expectancy. ⋯ We found no sex difference in baseline pain threshold or tolerance levels. When partitioned by sex and expectancy state, analgesia only occurred in males during positive expectancy states at 2, 3 and 4 h post-placebo, and at 1 and 2 h post-ibuprofen. The time course of analgesic action in males was as expected considering the pharmacokinetic profile of ibuprofen. Our study found that dosages of 800 mg of ibuprofen are ineffective in producing analgesia in women regardless of their expectations. We hypothesize that ibuprofen analgesia is produced by a combination of specific pharmacological effects and a non-specific beta endorphin-mediated placebo effect. Whatever the mechanism responsible for the analgesic response seen in males, this research re-emphasizes the importance of psychological factors in determining drug response. It also shows that these factors can differ between men and women, and thus the contribution of psychological factors on analgesia needs to be seriously re-evaluated.
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It is not known whether general practitioners (GPs) prescribe analgesic medication according to intensity of pain or a hierarchical prescribing regimen. ⋯ GPs do not always issue prescriptions for musculoskeletal pain. In cases where a prescription is issued, this is more strongly influenced by previous prescriptions than the patient's pain level. GPs adopt an individualized approach to the treatment of musculoskeletal pain in older adults.
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To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. ⋯ Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing.