Browse by Audience
Multicentre cross-sectional study.
Learn More >Evidence suggests that Δ-tetrahydrocannabinol (Δ-THC), the intoxicating component of cannabis, may cause enduring changes in the structure and function of adolescent brain circuits implicated in nociceptive responding. Yet, whether such changes might persistently disrupt nociceptive behaviors remains unknown. In the present study, we subjected C57BL6/J mice of both sexes to once-daily injections of Δ-THC (5 mg-kg, intraperitoneal) or vehicle throughout adolescence (PND 30-43) and, when the animals had reached adulthood (PND 70), assessed nociceptive behavior using the formalin and chronic constriction injury (CCI) tests. We also investigated, using the tail immersion test, the antinociceptive effects of morphine and the development of tolerance to such effects. The results show that adolescent Δ-THC exposure does not significantly impair nociceptive responding or morphine-related antinociception and tolerance. The findings suggest that frequent exposure to a moderate dose of Δ-THC during adolescence does not permanently alter nociceptive circuits in male or female mice. The endocannabinoid system serves critical functions in the central and peripheral nervous systems, including regulation of pain, and can be modified by prolonged exposure to the intoxicating constituent of cannabis, Δ-tetrahydrocannabinol (Δ-THC). This raises the possibility that regular use of Δ-THC-containing cannabis during adolescence might cause changes in nociception that persist into adulthood. We found that frequent early-life exposure to a moderate dose of Δ-THC does not permanently alter nociceptive function in male or female mice.
Learn More >Activation of spinal cord microglia contributes to the development of peripheral nerve injury-induced neuropathic pain. However, the molecular mechanisms underlying microglial function in neuropathic pain are not fully understood. We identified that the voltage-gated proton channel Hv1, which is functionally expressed in spinal microglia, was significantly increased after spinal nerve transection (SNT). Hv1 mediated voltage-gated proton currents in spinal microglia and mice lacking Hv1 (Hv1 KO) display attenuated pain hypersensitivities after SNT compared with wildtype (WT) mice. In addition, microglial production of reactive oxygen species (ROS) and subsequent astrocyte activation in the spinal cord was reduced in Hv1 KO mice after SNT. Cytokine screening and immunostaining further revealed that IFN-γ expression was compromised in spinal astrocytes in Hv1 KO mice. These results demonstrate that Hv1 proton channel contributes to microglial ROS production, astrocyte activation, IFN-γ upregulation, and subsequent pain hypersensitivities after SNT. This study suggests Hv1-dependent microglia-astrocyte communication in pain hypersensitivities and identifies Hv1 as a novel therapeutic target for alleviating neuropathic pain.
Learn More >Alloknesis, an abnormal itch sensation induced by innocuous stimuli, is a key phenomenon in the vicious itch-scratch cycle in patients with atopic dermatitis. Dry skin and pruritus, including alloknesis, are major health problems in peri- and post-menopausal women. We recently reported permeability barrier dysfunction in ovariectomised (OVX) mice-a model of menopause-and found that the dysfunction was related to dry skin. However, the mechanism of the itch remains unknown. Therefore, we examined touch- and pruritogen-evoked alloknesis and epidermal innervation in OVX mice and acetone, diethyl ether, and water (AEW)-treated mice, for the experimental dry skin model. Both alloknesis and epidermal innervation were comparable in OVX and AEW mice. Neutralising antibodies against IL-4 and IL-13 inhibited alloknesis in both OVX and AEW mice as early as 30 min after intradermal administration. Comparable values close to the measurement limit of IL-4 were found in the skin of HRT and Sham mice as well as AEW and the control mice, but the levels of IL-4 were within the measurement limit in OVX mice. We could not detect mRNAs of IL-4 or IL-13 in any groups of mice. On the other hand, the number of eosinophils and basophils was increased in OVX and AEW mice. These results suggest that impaired barrier function in cooperation with type 2 cytokines derived from eosinophils and basophils in the skin or with endogenous type 2 cytokine may trigger the development of alloknesis, and thus, these cytokines could be a therapeutic target for sensitive skin.
Learn More >In spite of the relevance of daily function in individuals with chronic pain, few questionnaires have been designed to assess this domain in individuals with musculoskeletal pain. In addition, the Impairment and Functioning Inventory (IFI-R) is the only instrument that assesses perceived decreases in levels of daily activity after the onset of pain.
Learn More >Concomitant with expanded legalization, cannabis is increasingly used to treat chronic pain among persons with HIV (PWH), despite equivocal benefit in research limited by small sample sizes and short duration of follow-up. To address these limitations, among a sample of PWH with pain interference enrolled in the Veterans Aging Cohort Study, we performed a target trial emulation study to compare the impact of four cannabis use strategies on pain interference. Among those receiving long-term opioid therapy (LTOT), we also explored impact of these strategies on ≥ 25% LTOT dose reduction. Among the analytic sample ( = 1284), the majority were men with a mean age of 50. Approximately 31% used cannabis and 12% received LTOT at baseline. Adjusting for demographic and clinical factors, cannabis use in any of 4 longitudinal patterns was not associated with resolved pain interference over 12- to 24-month follow-up. Among 153 participants receiving LTOT at baseline, cannabis use at both baseline and follow-up was negatively associated with LTOT dose reduction compared to no use at both baseline and follow-up. These findings support other observational studies finding no association between cannabis use and improved chronic pain or LTOT reduction among PWH.
Learn More >Identifying common genetic variants that confer genetic risk for cluster headache.
Learn More >Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD).
Learn More >To examine the association between subtypes of insomnia and the risk of chronic spinal pain.
Learn More >Bone cancer pain (BCP) was associated with microRNA dysregulation. In this study, we intended to clarify the potential role of miR-135-5p in a BCP mouse model, which was established by tumor cell implantation (TCI) in the medullary cavity of the mouse femur. The BCP-related behaviors were tested, including the paw withdrawal mechanical threshold (PWMT) and number of spontaneous flinches (NSF). The miRNA expression profiles in astrocytes of the sham and tumor groups were compared, and miRNA microarray and quantitative real-time PCR (qRT-PCR) assays confirmed that the amount of expression of miR-135-5p was significantly decreased in astrocytes of the tumor group. Gain- and loss-of-function studies showed that miR-135-5p could inhibit astrocyte activation and inflammation cytokine (TNF-α and IL-1β) expression. The relation between miR-135-5p and JAK2 was detected by bioinformatic analysis and dual luciferase reporter gene assay. By conducting in vitro experiments, it was shown that the miR-135-5P mimics lowered the level of JAK2/STAT3 proteins and inflammatory factors in astrocytes. Moreover, in vivo analysis on BCP mice model indicated that the miR-135-5p agonist could sufficiently increase PWMT and decrease NSF. Meanwhile, reduced activation of astrocytes in the spinal cord, as well as decreased expression of JAK2/STAT3 and inflammatory mediators, were found after miR-135-5p agonist treatment. Collectively, the results showed that miR-135-5p could potentially reduce BCP in mice through inhibiting astrocyte-mediated neuroinflammation and blocking of the JAK2/STAT3 signaling pathway, indicating that the upregulation of miR-135-5P could be a therapeutic focus in BCP treatment.
Learn More >