Browse by Audience
There is cumulating evidence that endothelin-1 (ET-1) may play a role in migraine, however controversial findings still impede a conclusion to be drawn. Herein we tested the hypothesis that endothelin ETB receptors are major contributors to migraine-like responses. ET-1, IRL-1620 (selective ETB receptor agonist) or CGRP were injected into the trigeminal ganglion (TG) of female Wistar rats, and the development of periorbital mechanical allodynia was assessed hourly with von Frey hairs. Twenty-four hours later, rats were exposed to an aversive light for 1 h, after which the reactivation of periorbital mechanical allodynia (indicating photic sensitivity) was assessed up to 4 h. Moreover, the effect of systemic Bosentan (ETA/ETB receptors antagonist) or the selective antagonists of ETA (BQ-123) and ETB (BQ-788) receptors injected into the TG were evaluated against CGRP-induced responses. ET-1 and IRL-1620 injection into the TG induced periorbital mechanical allodynia and photic sensitivity. Bosentan attenuated periorbital mechanical allodynia but failed to affect photic sensitivity induced by CGRP. Selective blockade of ETB receptors in the TG fully prevented the development of periorbital mechanical allodynia and photic sensitivity induced by CGRP, but ETA receptor blockade caused only a slight reduction of periorbital mechanical allodynia without affecting photic sensitivity. ETB receptor-operated mechanisms in the TG may contribute to migraine-like responses in female rats.
Learn More >This needs assessment study examined current processes of physiotherapy care for adults with back pain in a large teaching hospital serving a multicultural community in Sydney, Australia. Evaluation of current practices is a necessary first step in the design of a patient-centred, multidisciplinary service that promotes best practice in back pain management.
Learn More >Neuropathic pain (NP) is a challenging condition to treat, as the need for new drugs to treat NP is an unmet goal. We investigated the analgesic potential of a new sulfated disaccharide compound, named BIS014. Oral administration (p.o.) of this compound induced ameliorative effects in formalin-induced nociception and capsaicin-induced secondary mechanical hypersensitivity in mice, but also after partial sciatic nerve transection (spared nerve injury), chemotherapy (paclitaxel)-induced NP, and diabetic neuropathy induced by streptozotocin. Importantly, BIS014, at doses active on neuropathic hypersensitivity (60 mg/kg/p.o.), did not alter exploratory activity or motor coordination (in the rotarod test), unlike a standard dose of gabapentin (40 mg/kg/p.o.) which although inducing antiallodynic effects on the NP models, it also markedly decreased exploration and motor coordination. In docking and molecular dynamic simulation studies, BIS014 interacted with TRPV, a receptor involved in pain transmission where it behaved as a partial agonist. Additionally, similar to capsaicin, BIS014 increased cytosolic Ca concentration ([Ca]) in neuroblastoma cells expressing TRPV receptors; these elevations were blocked by ruthenium red. BIS014 did not block capsaicin-elicited [Ca] transients, but inhibited the increase in the firing rate of action potentials in bradykinin-sensitized dorsal root ganglion neurons stimulated with capsaicin. PERSPECTIVE: We report that the oral administration of a new sulfated disaccharide compound, named BIS014, decreases neuropathic pain from diverse etiology in mice. Unlike the comparator gabapentin, BIS014 does not induce sedation. Thus, BIS014 has the potential to become a new efficacious non-sedative oral medication for the treatment of neuropathic pain.
Learn More >An integrated score that globally assesses perioperative pain experience and rationally weights each component has not yet been developed.
Learn More >Although numerous studies have described botulinum toxin type A (BTX-A) efficacy against trigeminal neuralgia (TN), the underlying cellular mechanisms remain unclear. We have investigated cellular mechanisms that mediate the antinociceptive effect of BTX-A in a rodent model of TN produced by compression of the trigeminal nerve root (TNR). Anesthetized male Sprague-Dawley rats were fixed in a stereotaxic instrument and compression of the TNR was then achieved with a 4% agar solution. This model produced significant mechanical allodynia and increased the expression of hypoxia-inducible factor (HIF)-1α and cytokines levels including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the trigeminal ganglion (TG) by postoperative day (POD) 7. Single or double treatments with a high BTX-A dose (3 U/kg) led to significantly prolonged antinociceptive effects. Furthermore, a single treatment with BTX-A (3 U/kg) significantly suppressed the upregulation of HIF-1α expression and IL-1β, IL-6, and TNF-α concentrations in the TG. Intraganglionic injection of PX-12, a HIF-1α inhibitor, led to significant anti-allodynic effects and lowered the IL-1β, IL-6, and TNF-α levels in the TG. These findings indicate that the antinociceptive effect of BTX-A is mediated via HIF-1α associated cytokines modulation in the TG and is therefore a potentially relevant treatment strategy for TN. PERSPECTIVE: The antinociceptive properties of BTX-A in a rat model of trigeminal neuralgia are mediated through the regulation of the HIF-1α associated cytokine pathway in the trigeminal ganglion. BTX-A is therefore a potentially effective treatment strategy for trigeminal neuralgia.
Learn More >Quantitative sensory testing (QST) assesses the functional integrity of small and large nerve fibre afferents and central somatosensory pathways; QST was assumed to provide insight into the mechanisms of neuropathy. We analysed QST profiles and phenotypes in diabetes mellitus patients to study whether these could differentiate patients with and without pain and neuropathy.
Learn More >Neuropathic pain caused by nerve injury presents with severe spontaneous pain and a range of comorbidities, including deficits in higher executive functioning, none of which are adequately treated with current analgesics. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization. However, the roles of IL-6 in neuropathic pain and related comorbidities have yet to be fully clarified. The present study examined the effect of MR16-1, an anti-IL-6 receptor antibody and inhibits IL-6 activity, on allodynia and cognitive impairment in mice with neuropathic pain following partial sciatic nerve ligation (PSNL). Significant upregulation of IL-6 expression was observed in the hippocampus in PSNL mice. Intranasal administration of MR16-1 significantly improved cognitive impairment but not allodynia in PSNL mice. Intranasal MR16-1 blocked PSNL-induced degenerative effects on hippocampal neurons. Intraperitoneal administration of MR16-1 suppressed allodynia but not cognitive impairment of PSNL mice. The findings suggest that cognitive impairment associated with neuropathic pain is mediated through changes in hippocampus induced by IL-6. These data also suggest that IL-6 mediated peripheral inflammation underlies allodynia, and IL-6 mediated inflammation in the central nervous system underlies cognitive impairment associated with neuropathic pain, and further suggest the therapeutic potential of blocking IL-6 functioning by blocking its receptor.
Learn More >To understand patients' perspectives on living with dry eye disease (DED), and on the unmet needs in DED and chronic ocular surface pain (COSP) management.
Learn More >It is well recognized that underrepresented and minoritized groups do not have the same career opportunities. However, there are limited data on the range and specifics of potential barriers that withhold people in headache medicine and science from reaching their full potential. Moreover, people from different geographical regions often perceive different challenges. We aimed to identify world-wide perceived career barriers and possibilities for promoting equality amongst professionals in the headache fields.
Learn More >Mesenchymal stem cell (MSCs)-derived small Extracellular Vesicles (sEVs) are considered as a new cell-free therapy for pain caused by nerve injury, but whether human placental mesenchymal stem cell-derived sEVs relieve pain in sciatic nerve injury and its possible mechanism are still unclear. In this study, we investigated the roles of hPMSCs-derived sEVs and related mechanisms in neuropathic pain.
Learn More >