Browse by Audience
Chronic pain affects 1 in 5 people and has been shown to disrupt attention. Here, we investigated whether pain disrupts everyday decision making. In Study 1, 1322 participants completed two tasks online: a shopping decisions task and a measure of decision outcomes over the previous 10 years. Participants who were in pain during the study made more errors on the shopping task than those who were pain-free. Participants with a recurrent pain condition reported more negative outcomes from their past decisions than those without recurrent pain. In Study 2, 44 healthy participants completed the shopping decisions task with and without experimentally-induced pain. Participants made more errors while in pain than while pain-free. We suggest that the disruptive effect of pain on attending translates into poorer decisions in more complex and ecologically valid contexts, that the effect is causal, and that the consequences are not only attentional, but financial.
Learn More >Patients suffering from neuropathic pain have a higher incidence of depression and cognitive decline. Although environment enrichment (EE) may be effective in the treatment of neuropathic pain, the precise mechanisms underlying its actions remain determined. The aim of the study was to examine the molecular mechanisms underlying the EE's beneficial effects in mice with neuropathic pain. EE attenuated the pain threshold reduction, depression-like phenotype, and memory deficit in mice after chronic constriction injury (CCI). Furthermore, EE attenuated decreased neurogenesis and increased inflammation in the hippocampus of mice with neuropathic pain after CCI. Moreover, the suppression of adult hippocampal neurogenesis by temozolomide antagonized the beneficial effects of EE on depression-like phenotype and cognitive deficit in the mice with neuropathic pain. In addition, lipopolysaccharide-induced increase in tumor necrosis factor-α (TNF-α) in the hippocampus antagonized the beneficial effects of EE for these behavioral abnormalities in mice with neuropathic pain. Knock-down of NPAS4 (neuronal PAS domain protein 4) in the hippocampus by lentivirus targeting NPAS4 blocked these beneficial effects of EE in the mice with neuropathic pain. These all findings suggest that hippocampal NPAS4 plays a key role in the beneficial effects of EE on the pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain. Therefore, it is likely that NPAS4 would be a new therapeutic target for perceptional, affective, and cognitive dimensions in patients with chronic pain.
Learn More >Opioids are among the most effective and widely prescribed medications for the treatment of pain following spinal cord injury (SCI). Spinally-injured patients receive opioids within hours of arrival at the emergency room, and prolonged opioid regimens are often employed for the management of post-SCI chronic pain. However, previous studies in our laboratory suggest that the effects of opioids such as morphine may be altered in the pathophysiological context of neurotrauma. Specifically, we have shown that morphine administration in a rodent model of SCI increases mortality and tissue loss at the injury site, and decreases recovery of motor and sensory function, and overall health, even weeks after treatment. The literature suggests that opioids may produce these adverse effects by acting as endotoxins and increasing glial activation and inflammation. To better understand the effects of morphine following SCI, in this study we used flow cytometry to assess immune-competent cells at the lesion site. We observed a morphine-induced increase in the overall number of CD11b+ cells, with marked effects on microglia, in SCI subjects. Next, to investigate whether this increase in the inflammatory profile is necessary to produce morphine's effects, we challenged morphine treatment with minocycline. We found that pre-treatment with minocycline reduced the morphine-induced increase in microglia at the lesion site. More importantly, minocycline also blocked the adverse effects of morphine on recovery of function without disrupting the analgesic efficacy of this opioid. Together, our findings suggest that following SCI, morphine may exacerbate the inflammatory response, increasing cell death at the lesion site and negatively affecting functional recovery.
Learn More >Altered Toll-like receptor (TLR) 4 activation has been identified in several chronic pain conditions but has not been well studied in interstitial cystitis/bladder pain syndrome (IC/BPS). Our published human studies indicated that IC/BPS patients present altered systemic TLR4-mediated inflammatory responses, which were significantly correlated with reported pain severity. In this study, we sought to determine whether altered TLR4 activation plays a role in pelvic/bladder pain seen in IC/BPS patients using our validated IC/BPS-like transgenic autoimmune cystitis model (URO-OVA). URO-OVA mice developed responses consistent with pelvic and bladder pain after cystitis induction, which was associated with increased splenocyte production of TLR4-mediated proinflammatory cytokines interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF)-a. Increased spinal expression of mRNAs for proinflammatory cytokines IL-6 and TNF-a, glial activation markers CD11b and glial fibrillary acidic protein (GFAP), and endogenous TLR4 ligand high mobility group box 1 (HMGB1) was also observed after cystitis induction. Compared to URO-OVA mice, URO-OVA (TLR4-deficient URO-OVA) mice developed significantly reduced nociceptive responses, although similar bladder inflammation and voiding dysfunction, after cystitis induction. Intravenous administration of TAK-242 (a TLR4 selective antagonist) significantly attenuated nociceptive responses in cystitis-induced URO-OVA mice, which was associated with reduced splenocyte production of TLR4-mediated IL-1b, IL-6 and TNF-a as well as reduced spinal expression of mRNAs for IL-6, TNF-a, CD11b, GFAP, and HMGB1. Our results indicate that altered TLR4 activation plays a critical role in bladder nociception independent of inflammation and voiding dysfunction in the URO-OVA model, providing a potential mechanistic insight and a therapeutic target for IC/BPS pain.
Learn More >To introduce growth curve modeling for longitudinal headache research.
Learn More >To assess the level of resilience among patients with chronic musculoskeletal pain and their parents and to determine factors associated with patient and parental resilience.
Learn More >To review and highlight current literature on emerging acute migraine treatments, focusing on CGRP receptor antagonists, gepants, and 5-HT receptor agonists (ditans).
Learn More >Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that develops as a consequence of prolonged hyperglycaemia-induced injury to the long nerves. Apart from pain, PDN is also characterized by morphine hyposensitivity. Intriguingly, in streptozotocin (STZ)-induced diabetic rats exhibiting marked morphine hyposensitivity, dietary administration of the nitric oxide (NO) precursor, L-arginine at 1g/day, progressively rescued morphine efficacy and potency over an 8-week treatment period. In earlier work, single bolus doses of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde), evoked dose-dependent pain relief in STZ-diabetic rats but the efficacious doses were 3-4 orders of magnitude higher in advanced diabetes than that required in early STZ-diabetes. Together, these findings suggested a role for NO in the modulation of μ-opioid (MOP) receptor signalling. Therefore, the present study was designed to assess a role for NO released from PRG150, in modulating MOP receptor function in vitro. Here, we show an absolute requirement for the MOP receptor, but not the δ-opioid (DOP) or the κ-opioid (KOP) receptor, to transduce the cellular effects of PRG150 on forskolin-stimulated cAMP responses in vitro. PRG150 did not interact with the classical naloxone-sensitive binding site of the MOP receptor and its effects on cAMP responses in HEK-MOP cells were also naloxone-insensitive. Nevertheless, the inhibitory effects of PRG150 on forskolin-stimulated cAMP responses in HEK-MOP cells were dependent upon pertussis toxin (PTX)-sensitive G proteins as well as membrane lipid rafts and src kinase. Together, our findings implicate a role for NO in modulating MOP receptor function in vivo. This article is protected by copyright. All rights reserved.
Learn More >Based on previous clinic-based MRI studies showing regional differences in the cerebral cortex between those with and without headache, we hypothesized that headache sufferers have a decrease in volume, thickness or surface area in anterior cingulate cortex (ACC), prefrontal cortex (PFC), and insula. In addition, exploratory analyses on volume, thickness and surface area across the cerebral cortical mantle were performed. 1006 participants (50-66 years) from the general population were selected to an imaging study of the head at 1.5 T (HUNT-MRI). 283 individuals suffered from headache, 80 with migraine and 87 with tension-type headache, whereas 309 individuals did not suffer from headache and were used as controls. T1 weighted 3D scans of the brain were analysed with voxel-based morphometry and FreeSurfer. The association between cortical volume, thickness and surface area and questionnaire-based headache diagnoses was evaluated, taking into consideration evolution of headache and frequency of attacks. There were no significant differences in cortical volume, thickness or surface area between headache sufferers and non-sufferers in ACC, PFC or insula. Similarly, the exploratory analyses across the cortical mantle demonstrated no significant differences in volume, thickness or surface area between any of the headache groups and the non-sufferers. Maps of effect sizes showed small differences in the cortical measures between headache sufferers and non-sufferers. Hence, there are probably no or only very small differences in volume, thickness or surface area of the cerebral cortex between those with and without headache in the general population.
Learn More >