These results suggest that regular aerobic exercise alone, in comparison with placebo, is associated with significant clinical improvement in patients suffering from panic disorder, but that it is less effective than treatment with clomipramine.
C-fiber nociceptors can be divided into two groups based on growth factor dependency and isolectin B4 (IB4) binding. IB4-negative nociceptors have been proposed to contribute to inflammatory pain. Since the TRPV1 receptor is critical for inflammatory heat hyperalgesia, we hypothesized that inflammation would sensitize IB4 negative but not IB4-positive small-diameter neurons to TRPV1 stimuli. Two days after complete Freund's adjuvant (CFA)-induced inflammation in the hind paw of mice, lumbar 4/5 ganglia were dissociated and small-diameter (=26 microm) neurons were quantified for responsiveness to the TRPV1 agonists, capsaicin and protons using patch clamp recordings. Surprisingly, inflammation did not alter the responsiveness of IB4-negative neurons to capsaicin or protons. Conversely, inflammation increased the percentage of IB4-positive neurons that responded to 1 microM capsaicin from 24 to 80% and increased the percentage that responded to pH 5.0 from 54 to 85%. In parallel, inflammation increased the percentage of IB4-positive neurons that was TRPV1-immunoreactive. The inflammation-induced increase in capsaicin- and proton-responsiveness was entirely mediated by TRPV1 because IB4-positive neurons from inflamed TRPV1-/- mice were capsaicin-insensitive and unaltered in proton-responsiveness. Interestingly, comparison of neurons from TRPV1+/+ and TRPV1-/- mice revealed that the sustained proton-evoked currents in IB4-positive neurons were independent of TRPV1 whereas the sustained-only proton currents in IB4-negative neurons were TRPV1-dependent. Together, these data indicate that TRPV1 function and expression are selectively increased in IB4-positive neurons during inflammation in mouse and suggest a novel role for IB4-positive C-fibers during inflammation.
Thalidomide reduces thermal hyperalgesia and mechanical allodynia in chronic constrictive sciatic nerve injury (CCI). Since thalidomide mainly inhibits tumor necrosis factor alpha (TNF-alpha) synthesis with less well defined effects on other cytokines, we investigated the effect of the drug on the expression of the proinflammatory cytokines TNF-alpha, interleukin-1beta (IL-1beta) and interleukin 6 (IL-6), and of the anti-inflammatory cytokine interleukin-10 (IL-10) in the lesioned rat sciatic nerve. The increase of endoneurial TNF-alpha during the first week after CCI was reduced after thalidomide treatment, as shown with immunohistochemistry and enzyme-linked-immunosorbent assay. In contrast, endoneurial IL-1beta-immunoreactivity (IR) and IL-6-IR were not altered by thalidomide treatment, nor was macrophage influx. Recruitment of epineurial IL-10 immunoreactive macrophages as well as the recovery of injury-induced depletion of endoneurial IL-10-IR was enhanced by thalidomide treatment. To control for central plasticity as another factor for the effects of thalidomide, the spinal cord was analyzed for changes in neurotransmitters. The decrease in CGRP-IR and SP-IR in the dorsal horn of operated animals was not influenced by treatment. In contrast, the increase in met-enkephalin observed in the dorsal horn of operated animals was further enhanced in the thalidomide-treated animals. The study elucidates some of the complex alterations in CCI and its modulation by thalidomide, and provides further evidence for a possible therapeutic benefit of cytokine-modulating substances in the treatment of neuropathic pain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.