Pain
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Transient receptor potential vanilloid 1 (TRPV1) is highly expressed in primary afferent neurons. Tissue damage generates an array of chemical mediators that activate and sensitize afferent nerve fibers, and sensitization of afferent nerve fibers plays an important role in development of visceral pain. We investigated participation of TRPV1 in visceral pain associated with bladder inflammation induced in mice by systemic treatment with cyclophosphamide or intravesical instillation of acrolein. ⋯ Cystitis did not affect the threshold of response to thermal stimuli in WT or KO mice. These results suggest that TRPV1 is essential for cystitis-induced bladder mechanical hyperreactivity. Also, TRPV1 participates in development of visceral pain, as reflected by referred increased mechanosensitivity in peripheral tissues in the presence of visceral inflammation.
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Comparative Study
The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain.
It has been postulated that the G protein-coupled receptor, GPR55, is a third cannabinoid receptor. Given that the ligands at the CB(1) and CB(2) receptors are effective analgesic and anti-inflammatory agents, the role of GPR55 in hyperalgesia associated with inflammatory and neuropathic pain has been investigated. As there are no well-validated GPR55 tool compounds, a GPR55 knockout (GPR55(-/-)) mouse line was generated and fully backcrossed onto the C57BL/6 strain. ⋯ This suggests that GPR55 signalling can influence the regulation of certain cytokines and this may contribute to the lack of inflammatory mechanical hyperalgesia in the GPR55(-/-) mice. In the model of neuropathic hypersensitivity, GPR55(-/-) mice also failed to develop mechanical hyperalgesia up to 28 days post-ligation. These data clearly suggest that the manipulation of GPR55 may have therapeutic potential in the treatment of both inflammatory and neuropathic pain.
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Comparative Study
Oxidative stress in the spinal cord is an important contributor in capsaicin-induced mechanical secondary hyperalgesia in mice.
Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, thus suggesting ROS involvement in central sensitization. To investigate ROS involvement in central sensitization, the effects of ROS scavengers and donors on pain behaviors were examined in mice. Capsaicin- induced hyperalgesia was used as a pain model since it has 2 distinctive pain components, primary and secondary hyperalgesia representing peripheral and central sensitization, respectively. ⋯ On the other hand, intrathecal injection of tert-butylhydroperoxide (t-BOOH, 5 microl), a ROS donor, produced a transient hyperalgesia in a dose-dependent manner. The number of MitoSox positive dorsal horn neurons was increased significantly after capsaicin treatment. This study suggests that ROS mediates the development and maintenance of capsaicin-induced hyperalgesia in mice, mainly through central sensitization and that the elevation of spinal ROS is most likely due to increased production of mitochondrial superoxides in the dorsal horn neurons.
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Comparative Study
Onset, prognosis and risk factors for widespread pain in schoolchildren: a prospective 4-year follow-up study.
Little is known about the epidemiology of widespread pain (WSP) in children and adolescents. This study aims to estimate the new-onset and prognosis of WSP in schoolchildren and investigate factors predicting its development. A prospective study was conducted among 1756 schoolchildren (age 10-12 years) in Southern Finland. ⋯ Of the children who were free of WSP at baseline, 18% reported new-onset WSP at 1-year follow-up and 3% reported these symptoms at both follow-up times. The independent baseline risk factors of WSP were older age (OR 1.3 95% CI 1.0-1.8), female gender (OR 1.4, 1.1-1.9), depressiveness (OR 1.5, 1.1-2.2) and regional back pain symptoms (Neck pain: OR 1.7, 1.1-2.4; Upper back pain: OR 2.1, 1.1-4.1; Lower back pain: OR 3.0, 1.6-5.7). Both psychological factors and somatic pain symptoms predict future development of WSP in adolescents.
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Comparative Study
A prospective identification of neuropathic pain in specific chronic polyneuropathy syndromes and response to pharmacological therapy.
Although many pharmacological agents are used in the therapy of neuropathic pain (NeP) due to polyneuropathy (PN), there are limited comparison studies comparing these agents. We evaluated patients with PN and related NeP in a tertiary care neuromuscular clinic with prospective follow-up after 3 and 6 months for degree of NeP using a Visual Analog Score (VAS). Clinical response to specific open-label pharmacotherapies was measured and compared for those patients not receiving pharmacotherapy. ⋯ Approximated numbers needed to treat were similar between different individual oral pharmacotherapies, trending towards greater treatment efficacy with combination therapy. NeP is common in patients with PN and frequently requires pharmacotherapy management, which may be more effective with combination therapy. Future studies assessing longer duration of follow-up and quality of life changes with the use of various pharmacotherapies for management of NeP due to PN will be important.