The journal of pain : official journal of the American Pain Society
-
Many derivatives of bisphosphonates, which are inhibitors of bone resorption, have been developed as promising agents for painful pathologies in patients with bone resorption-related diseases. The mechanism for pain relief by bisphosphonates remains uncertain. Studies have reported that bisphosphonates could reduce central neurochemical changes involved in the generation and maintenance of bone cancer pain. In this study, we hypothesized that bisphosphonates would inhibit spinal microglial activation and prevent the development of hyperalgesia caused by peripheral tissue injury. We investigated the effects of alendronate (a nitrogen-containing bisphosphonate) on the development of neuropathic pain and its role in modulating microglial activation in vivo and in vitro. Intrathecal and intraperitoneal administration of alendronate relieved neuropathic pain behaviors induced by chronic constriction sciatic nerve injury. Alendronate also significantly attenuated spinal microglial activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation without affecting astrocytes. In vitro, alendronate downregulated phosphorylated p38 and phosphorylated extracellular signal regulated kinase expression in lipopolysaccharide-stimulated primary microglia within 1 hour, and pretreatment with alendronate for 12 and 24 hours decreased the expression of inflammatory cytokines (tumor necrosis factor α, and interleukins 1β and 6). These findings indicate that alendronate could effectively relieve chronic constriction sciatic nerve injury-induced neuropathic pain by at least partially inhibiting the activation of spinal microglia and the p38 MAPK signaling pathway. ⋯ Alendronate could relieve neuropathic pain behaviors in animals by inhibiting the activation of spinal cord microglia and the p38 MAPK cell signaling pathway. Therapeutic applications of alendronate may be extended beyond bone metabolism-related disease.
-
Previous studies have not examined the assessment of chronic low back pain (CLBP) and pain-related anxiety from a fear avoidance model through the use of motion-capture software and virtual human technologies. The aim of this study was to develop and assess the psychometric properties of an interactive, technologically based hierarchy that can be used to assess patients with pain and pain-related anxiety. We enrolled 30 licensed physical therapists and 30 participants with CLBP. Participants rated 21 video clips of a 3-D animated character (avatar) engaging in activities that are typically feared by patients with CLBP. The results of the study indicate that physical therapists found the virtual hierarchy clips acceptable and depicted realistic patient experiences. Most participants with CLBP reported at least 1 video clip as being sufficiently anxiety-provoking for use clinically. Therefore, this study suggests a hierarchy of fears can be created out of 21 virtual patient video clips paving the way for future clinical use in patients with CLBP. ⋯ This report describes the development of a computer-based virtual patient system for the assessment of back pain-related fear and anxiety. Results show that people with back pain as well as physical therapists found the avatar to be realistic, and the depictions of behavior anxiety- and fear-provoking.