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Some patients with migraine, particularly those in primary care, require effective, well-tolerated, migraine-specific oral preventive treatments.
Learn More >Elevated intracranial pressure (ICP) is observed in many brain disorders. Obesity has been linked to ICP pathogenesis in disorders such as idiopathic intracranial pressure (IIH). We investigated the effect of diet induced obesity (DIO) on ICP and clinically relevant sequelae. Rats were fed either a control or high fat diet. Following weight gain long term ICP, headache behavior, body composition and retinal outcome were examined. Post-hoc analysis of retinal histology and molecular analysis of choroid plexus and trigeminal ganglion (TG) were performed. DIO rats demonstrated raised ICP by 55% which correlated with the abdominal fat percentage and increased non-respiratory slow waves, suggestive of altered cerebral compliance. Concurrently, DIO rats demonstrated a specific cephalic cutaneous allodynia which negatively correlated with the abdominal fat percentage. This sensitivity was associated with increased expression of headache markers in TG. Additionally, DIO rats had increased retinal nerve fiber layer thickness in vivo associated with raised ICP with a subsequent post-hoc demonstration of neuroretinal degeneration. This study demonstrates for the first time that DIO leads to raised ICP and subsequent clinically relevant symptom development. This novel model of non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP such as IIH.
Learn More >Treatment for childhood Complex Regional Pain Syndrome (CRPS) is associated with long-term recovery. The present study aimed to investigate the long-term biopsychosocial status and quality of life in young adolescents and adults after the treatment of childhood CRPS.
Learn More >Peripheral tissue damage and associated inflammation can trigger neuroplastic changes in somatic pain pathways, such as reduced neuronal firing thresholds and synaptic potentiation, that ultimately lead to peripheral sensitization and chronic pain. Electroacupuncture (EA) can relieve chronic inflammatory pain, but the underlying mechanisms are unknown, including the contributions of higher pain centers such as somatosensory cortex (SSC). We investigated these mechanisms using optogenetic modulation of SSC activity in a mouse inflammatory pain model. Injection of Complete Freund's Adjuvant into the hind paw reliably induced inflammation accompanied by reduced mechanical and thermal pain thresholds (hyperalgesia) within three days (mechanical: 1.54 ± 0.13 g; thermal: 3.94 ± 0.43 s). Application of EA produced significant thermal and mechanical analgesia, but these responses were reversed by optogenetic activation of SSC neurons, suggesting that EA-induced analgesia involves modulation of central pain pathways. Western blot and immunostaining revealed that EA also attenuated CaMKIIα signaling in the dorsal root ganglion, central spinal cord, SSC, and anterior cingulate cortex (ACC). In contrast, optogenetic activation of the SSC induced CaMKIIα signaling in SSC and ACC. These findings suggest that AE can relieve inflammatory pain by suppressing CaMKIIα-dependent plasticity in cortical pain pathways. The SSC and ACC CaMKIIα signaling pathways may be valuable therapeutic targets for chronic inflammatory pain treatment.
Learn More >Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90 s at 5 or 30 Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30 Hz EES at C4 and 5 Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5 Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30 Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30 Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.
Learn More >Spinal cord stimulation (SCS) can impact sensory, pain and tolerance thresholds in various ways, which can be accessed via quantitative sensory testing (QST). The objectives of this study were to (1) assess the subjective sensory responses using QST in patients following SCS therapy for PSPS and (2) to get a clinical impression of the results of SCS during an interview of these patients with PSPS and SCS during long term follow-up.
Learn More >Intensive Interdisciplinary Pain Treatment (IIPT) for youth with high impact chronic pain has been found to be effective in improving child symptoms and functioning. However, it is unclear how these interventions impact the parents' own well-being, as well as cognitions and behaviors which are known to influence child pain and functioning. Thus, the current study sought to determine the effect of IIPT on parent mental health, cognitions, and behaviors in parents of youth attending IIPT with their child.
Learn More >The heterogeneity of migraine has been reported extensively, with identified subgroups usually based on symptoms. Grouping individuals with migraine and similar comorbidity profiles has been suggested, however such segmentation methods have not been tested using real-world clinical data.
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