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Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) that exerts analgesic and anti-inflammatory actions. The transient receptor potential ankyrin 1 (TRPA1) channel, expressed primarily in nociceptors, mediates the action of proalgesic and inflammatory agents. Ibuprofen metabolism yields the reactive compound, ibuprofen-acyl glucuronide, which, like other TRPA1 ligands, covalently interacts with macromolecules. To explore whether ibuprofen-acyl glucuronide contributes to the ibuprofen analgesic and anti-inflammatory actions by targeting TRPA1, we used in vitro tools (TRPA1-expressing human and rodent cells) and in vivo mouse models of inflammatory pain. Ibuprofen-acyl glucuronide, but not ibuprofen, inhibited calcium responses evoked by reactive TRPA1 agonists, including allyl isothiocyanate (AITC), in cells expressing the recombinant and native human channel and in cultured rat primary sensory neurons. Responses by the non-reactive agonist, menthol, in a mutant human TRPA1 lacking key cysteine-lysine residues, were not affected. In addition, molecular modeling studies evaluating the covalent interaction of ibuprofen-acyl glucuronide with TRPA1 suggested the key cysteine residue C621 as a probable alkylation site for the ligand. Local administration of ibuprofen-acyl glucuronide, but not ibuprofen, in the mouse hind paw attenuated nociception by AITC and other TRPA1 agonists and the early nociceptive response (phase I) to formalin. Systemic ibuprofen-acyl glucuronide and ibuprofen, but not indomethacin, reduced phase I of the formalin response. Carrageenan-evoked allodynia in mice was reduced by local ibuprofen-acyl glucuronide, but not by ibuprofen, whereas both drugs attenuated PGE levels. Ibuprofen-acyl glucuronide, but not ibuprofen, inhibited the release of IL-8 evoked by AITC from cultured bronchial epithelial cells. The reactive ibuprofen metabolite selectively antagonizes TRPA1, suggesting that this novel action of ibuprofen-acyl glucuronide might contribute to the analgesic and anti-inflammatory activities of the parent drug.
Learn More >A study published in PAIN in 2010 showed remarkable effects of intradiscal methylene blue (MB) injections compared with placebo on pain intensity in patients with chronic discogenic low back pain (CD-LBP). Both groups received lidocaine hydrochloride injections for pain associated with the procedure. We replicated the design of the previously published study and performed a multicenter, double-blind, randomized, placebo-controlled trial to assess whether the extraordinary effects of MB on pain intensity could be confirmed. The primary outcomes were treatment success defined as at least 30% reduction in pain intensity and the Patients' Global Impression of Change 6 months after the intervention. We included 84 patients with CD-LBP of which 14 (35%) in the MB plus lidocaine group showed treatment success compared with 11 (26.8%) in the control group who received placebo plus lidocaine (P = 0.426). Twenty-seven percent of all participants treated with MB stated that their overall health improved much or very much (Patients' Global Impression of Change), vs 25.6% in the placebo group (P = 0.958). We were unable to confirm that intradiscal MB injections are better capable of significantly reducing pain in patients with CD-LBP 6 months after treatment compared with placebo. We observed that over one-quarter of patients receiving only lidocaine injections reported treatment success, which is in contrast with the previously published study. Our results do not support the recommendation of using intradiscal MB injections for patients with CD-LBP.
Learn More >To investigate the role of calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide in cluster headache, we measured these vasoactive peptides interictally and during experimentally induced cluster headache attacks.
Learn More >Opioid misuse is a significant public health problem. Chronic pain is one highly prevalent factor that is strongly associated with increased risk for opioid misuse. Anxiety sensitivity (fear of anxiety related physical sensations) is an individual difference factor consistently linked to pain experience, and separately, heroin use. The present study examined if anxiety sensitivity may be one factor related to the relationship between pain intensity and opioid misuse among opioid-using adults with chronic pain. Results indicated that anxiety sensitivity total score was significantly associated with the relationship between pain intensity and current opioid misuse, as well as pain intensity and severity of opioid dependence. Overall, results suggest that anxiety sensitivity may be an important assessment and intervention target to ultimately reduce the rates of opioid misuse among adults with chronic pain.
Learn More >Most drug epidemics in the United States have disproportionately affected nonwhite communities. Notably, the current opioid epidemic is heavily concentrated among low-income white communities, and the roots of this racial/ethnic phenomenon have not been adequately explained.
Learn More >To characterize the short-term prognosis of a clinical population of pediatric and young adult patients with migraine and explore predictors of clinical worsening while in care.
Learn More >The aims of this study were: 1, to investigate the association between the rs4680 Val158Met polymorphism in frequent episodic (FETTH) and chronic (CTTH) tension-type headache; and 2, to analyse the association between the rs4680 Val158Met polymorphism with clinical, psychological, or psychophysical variables.
Learn More >To describe and analyze Twitter activity associated with American Headache Society (AHS) conferences and evaluate the potential for Twitter to promote education and public outreach.
Learn More >The reason why some individuals develop chronic symptoms, whiplash-associated disorder, following whiplash trauma is poorly understood. We explored whether precollision pain-related diagnoses, medically unexplained symptoms, and psychiatric diagnoses are related to whiplash-associated disorder.
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