Browse by Audience
Traumatic injury is a major source of chronic pain, particularly for individuals with traumatic fracture of the fibula and/or tibia (lower extremity fracture) [LEFx]. Although several factors (e.g., older age, being female sex, high pain intensity at time of initial injury) have been identified as risk factors for chronic pain associated with LEFx. Comprehensive biopsychosical models to predict the odds of transitioning from acute to chronic pain after LEFx are needed to better understand the underlying processes, predict risk for chronic pain, and develop personalized therapies for individuals at higher risk for developing chronic pain.
Learn More >The midbrain periaqueductal grey (PAG) plays a central role in modulating pain through a descending pathway that projects indirectly to the spinal cord via the rostroventral medial medulla (RVM). While opioids are potent analgesics that target the PAG, their cellular actions on descending projection neurons are unclear.
Learn More >To characterize phenotypes of a novel CACNA1A mutation causing familial hemiplegic migraine type 1.
Learn More >Chronic itch can be extremely devastating and, in many cases, difficult to treat. One challenge in treating itch disorders is the limited understanding of the multitude of chemical players involved in the communication of itch sensation from the peripheral to central nervous system. Neuropeptides are intercellular signaling molecules that are known to be involved in the transmission of itch signals from primary afferent neurons, which detect itch in the skin, to higher-order circuits in the spinal cord and brain. To investigate the role neuropeptides play in transmitting itch signals, we generated two mouse models of chronic itch-Acetone-Ether-Water (AEW, dry skin) and calcipotriol (MC903, atopic dermatitis). For peptide identification and quantitation, we analyzed the peptide content of dorsal root ganglia (DRG) and dorsal horn (DH) tissues from chronically itchy mice using liquid chromatography coupled to tandem mass spectrometry. De novo-assisted database searching facilitated the identification and quantitation of 335 peptides for DH MC903, 318 for DH AEW, 266 for DRG MC903, and 271 for DRG AEW. Of these quantifiable peptides, we detected 30 that were differentially regulated in the tested models, after accounting for multiple testing correction (q<0.1). These include several peptide candidates derived from neuropeptide precursors, such as proSAAS, protachykinin-1, proenkephalin and calcitonin gene-related peptide, some of them previously linked to itch. The peptides identified in this study may help elucidate our understanding about these debilitating disorders. Data are available via ProteomeXchange with identifier PXD015949.
Learn More >Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain.
The objective was to systematically review the efficacy and safety of topically applied diclofenac in both acute and chronic musculoskeletal pain in adults. We used standard Cochrane methods. Searches were conducted in MEDLINE, EMBASE, and the Cochrane Register of Studies; the date of the final search was November 2018. Included studies had to be randomised and double blinded, with ten or more participants per treatment arm. Risk of bias was assessed. The primary outcome of "clinical success" was defined as participant-reported reduction in pain of at least 50%. Details of adverse events (AE) and numbers of withdrawals due to lack of efficacy (LoE) or AE were recorded. For acute pain, 23 studies (5170 participants) were included. All participants were treated for at least 5 days; most were treated for 7-14 days. Compared to placebo, number needed to treat (NNT) for different formulations were as follows: diclofenac flector plaster, 4.7 (95%CI 3.7-6.5); diclofenac plaster with heparin, 7.4 (95%CI 4.6-19); and diclofenac emulgel, 1.8 (95%CI 1.5-2.1).4.7% (65/1373) participants reported a systemic AE; 4.1% (78/1919) reported a local AE; and 1.3% (14/1063) withdrew due to an AE. Few participants withdrew due to LoE.For chronic pain, 21 studies (26 publications) with 5995 participants were included. The majority of studies focused on knee osteoarthritis pain. Formulations of diclofenac included gel, solution with or without DMSO, emulsion, and plaster. A clinical success rate of approximately 60% (NNT 9.5 [95%CI 7-14.7]) was achieved with a variety of diclofenac formulations. Local AEs (approximately 14%) were similar for both diclofenac and placebo. Event rate for systemic events was approximately 10%. Few serious events were reported, and between 0% and 17% of participants withdrew due to AEs. AEs were likely higher in the chronic group because participants were exposed to treatment for weeks rather than days. This large systematic review of over 11,000 participants demonstrates that topical diclofenac is effective for acute pain, such as sprains and strains, with minimal AEs. The effectiveness of topical diclofenac was also demonstrated in chronic musculoskeletal pain, such as osteoarthritis, but with a higher NNT (worse) compared with acute pain. Again, the incidence of AEs was low. Formulation does play a part in effectiveness, and studies are needed to investigate this further. Studies of chronic pain outside of osteoarthritis would also be helpful.
Learn More >Itch (pruritus), specifically chronic itch associated with disease conditions, significantly impairs the patient's quality of life. At present, the mechanisms underlying this aversive experience are still unclear, and the effective treatment of itch is largely unmet. Here, we report that intragastrical administration of bulleyaconitine A (BLA), which has been used for treating chronic pain for 30 years in China, inhibited itch-like behaviors induced by intradermal injection of histamine and chloroquine in mice and rats, dose-dependently. We found that a single application of the pruritic agents at the skin region innervated by the sural nerve induced long-term potentiation (LTP) of C-fiber field potentials evoked by the stimulation of the same nerve in the spinal dorsal horn of rats. The spinal LTP was remarkably reversed by the spinal application of either BLA or gastrin-releasing peptide receptor (GRPR) antagonist (PD176252). The effect of PD176252 was completely occluded by BLA, while the effect of BLA was only partially occluded by PD176252. Repetitive injection (daily, for four days) of either histamine or chloroquine in the back of the neck enhanced scratching behaviors progressively, and the itch sensitization persisted for at least one week after the discontinuation of the injections. The behavioral change was accompanied with the potentiation of C-fiber synaptic transmission in the dorsal horn. Both the itch sensitization and synaptic potentiation were substantially attenuated by intragastrical BLA. Together, BLA was effective in inhibiting histamine-dependent and histamine-independent itches, and the mechanisms underlying these effects were involved but not limited to the inhibition of GRP-GRPR signaling in the spinal dorsal horn.
Learn More >Migraine is defined by attacks of headache with a specific length and associated symptoms such as photophobia, phonophobia and nausea. It is long recognized that migraine is more than just the attacks and that migraine should be understood as a cycling brain disorder with at least 4 phases: interictal, preictal, ictal and postictal. However, unlike the pain phase, the other phases are less well defined, which renders studies focusing on these phases susceptible to bias. We herewith review the available clinical, electrophysiological, and neuroimaging data and propose that the preictal phase should be defined as up to 48 hours before the headache attack and the postictal phase as up to 24 hours following the ictal phase. This would allow future studies to specifically investigate these migraine phases and to make study results more comparable.
Learn More >Prescribers are often confronted with the decision to escalate opioid doses to achieve adequate analgesia. Understanding the impact of dose escalation on pain intensity is warranted. Using a retrospective cohort study design, Veterans with chronic pain and chronic opioid therapy were identified. Opioid dose escalators (>20% increase in average morphine milligram equivalent [MME] daily dose) were compared to dose maintainers (±20% change in average MME daily dose) assessed over two consecutive 6 month windows. Pain intensity was measured by the Numeric Rating Scale (NRS). The primary analyses used linear repeated measures models among a 1:1 matched sample of escalators and maintainers matched on propensity score and within ±180 days of the index date. Sensitivity analyses were conducted using adjusted linear repeated measures models with and without incorporating stabilized inverse probability of treatment weighting (SIPTW). There were 32,420 dose maintainers and 20,767 dose escalators identified with 19,358 (93%) matched pairs. Pain scores were persistently higher among dose escalators at each 90 day time period after the index date (0-90 Days After Index Date: Dose Escalators:4.68, 95%CI: 4.64, 4.72 Dose Maintainers:4.32, 95%CI: 4.28, 4.36, p<0.0001; 91-180 Days After Index Date: Dose Escalators:4.53, 95%CI: 4.49, 4.57; Dose Maintainers:4.25, 95%CI: 4.22, 4.29, p<0.0001) but were not different in the 90 days prior to the index date (Dose Escalators:4.64, 95%CI: 4.61, 4.68; Dose Maintainers:4.59, 95%CI: 4.55, 4.63, p=0.0551). Sensitivity analyses provided similar results as the primary analyses. Opioid dose escalation among patients with chronic pain is not associated with improvements in NRS pain scores.
Learn More >To evaluate the long-term safety and tolerability of ubrogepant for the acute treatment of migraine.
Learn More >The efficacy and safety of high-dose intravenous immunoglobulin (IVIG) in treatment-resistant diabetic painful polyneuropathy (DPN) were assessed.
Learn More >