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Vestibular migraine (VM) is considered the most common cause of spontaneous episodic vertigo and the second most common cause of vertigo. However, without a biomarker or a complete understanding of the pathophysiology, VM remains underrecognized and underdiagnosed. Therefore, definite diagnostic criteria are urgently needed. Meanwhile, VM should be clearly differentiated from other similar diseases. This paper may help clinicians improve the diagnostic rate of VM and reduce the rate of misdiagnosis. A PubMed search was performed using the following terms: vestibular migraine, migraine-associated vertigo/dizziness, migraine-related vertigo, migraine-related vestibulopathy, benign recurrent vertigo, vertiginous migraine, migraine, headache, vertigo, dizziness, and diagnosis. This paper also summarizes the diagnostic criteria and differential diagnoses of VM. The diagnosis of VM is based on the symptoms, degree, frequency, and duration of the vestibular episodes, a history of migraine, and the temporal association of migraine symptoms with vestibular episodes in at least 50% of cases, while ruling out what may be due to other reasons. In addition to vestibular symptoms and migraine, transient auditory symptoms, nausea, vomiting, and susceptibility to motion sickness may also be associated with VM. Thus, VM should be differentiated from other diseases such as Meniere's disease, benign paroxysmal positional vertigo, migraine with brainstem aura, vestibular neuritis, posterior circulation ischemia, multiple lacunar infarction, vestibular paroxysmia, motion sickness, and episodic ataxia type 2.
Learn More >Erenumab is a monoclonal antibody acting against calcitonin gene-related peptide receptor which has been found effective even for the treatment of chronic migraine (CM) complicated with medication overuse headache (MOH). According to the present guidelines, the treatment with erenumab should continue for up to 1 year. The aim of the present study is to explore the evolution of patients affected by CM and MOH at the baseline, after erenumab discontinuation.
Learn More >The development of painful paclitaxel-induced peripheral neuropathy (PIPN) represents a major dose-limiting side effect of paclitaxel chemotherapy. Here we report a promising effect of duvelisib (Copiktra™), a novel FDA approved PI3Kδ/γ isoform-specific inhibitor, in preventing paclitaxel-induced pain-like behaviour and pronociceptive signalling in dorsal root ganglia (DRG) and spinal cord dorsal horn (SCDH) in rat and mouse model of PIPN. Duvelisib blocked the development of mechanical hyperalgesia in both males and females. Moreover, duvelisib prevented paclitaxel-induced sensitization of TRPV1 receptors, increased PI3K/Akt-signalling in small-diameter DRG neurons and an increase of CD68 cells within DRGs. Specific optogenetic stimulation of inhibitory neurons combined with patch-clamp recording revealed that duvelisib inhibited paclitaxel-induced weakening of inhibitory, mainly glycinergic control on SCDH excitatory neurons. Enhanced excitatory and reduced inhibitory neurotransmission in the SCDH following PIPN was also alleviated by duvelisib application. In summary, duvelisib showed a promising ability to prevent neuropathic pain in PIPN. The potential use of our findings in human medicine may be augmented by the fact that duvelisib is an FDA approved drug with known side effects.We show that duvelisib, a novel FDA approved PI3Kδ/γ isoform-specific inhibitor, prevents the development of paclitaxel-induced pain-like behaviour in males and females and prevents pronociceptive signalling in dorsal root ganglia and spinal cord dorsal horn in rat and mouse model of paclitaxel-induced peripheral neuropathy.
Learn More >Inflammatory and neuropathic-like components underlie rheumatoid arthritis (RA)-associated pain and lysophosphatidic acid (LPA) is linked to both joint inflammation in RA patients and to neuropathic pain. Thus, we investigated a role for LPA signalling using the collagen antibody-induced arthritis (CAIA) model. Pain-like behavior during the inflammatory phase and the late, neuropathic-like phase of CAIA was reversed by a neutralizing antibody generated against LPA and by an LPA receptor inhibitor, but joint inflammation was not affected. Autotaxin, an LPA synthesizing enzyme was upregulated in dorsal root ganglia (DRG) neurons during both CAIA phases, but not in joints or spinal cord. Late-phase pronociceptive neurochemical changes in the DRG were blocked in Lpar1 receptor deficient mice and reversed by LPA neutralization. In vitro and in vivo studies indicated that LPA regulates pain-like behavior via the LPA receptor on satellite glia cells (SGCs), which is expressed by both human and mouse SGCs in the DRG. Furthermore, CAIA-induced SGC activity is reversed by phospholipid neutralization and blocked in Lpar1 deficient mice. Our findings suggest that the regulation of CAIA-induced pain-like behavior by LPA signalling is a peripheral event, associated with the DRGs and involving increased pronociceptive activity of SGCs, which in turn act on sensory neurons.
Learn More >Neuropathic pain is the most prevalent form of chronic pain caused by a disease of the nervous system, such as diabetic polyneuropathy. ɑ-Lipoic acid (ALA) is an antioxidant that has been widely studied for the treatment of pain symptoms in diverse conditions. Therefore, this study aimed to investigate the efficacy of ALA in the treatment of different types of pain through a systematic review and meta-analysis of randomized clinical trials. The study protocol was registered in the International Prospective Registry of Systematic Reviews (CRD42021261971). A search of the databases resulted in 1154 articles, 16 of which were included in the review (9 studies with diabetic polyneuropathy and 7 studies with other painful conditions). Most of the included studies had a low risk of bias. ALA showed efficacy for the treatment of headache, carpal tunnel syndrome and burning mouth syndrome. Meta-analysis was conducted only with the studies using diabetic polyneuropathy. Compared to placebo, ALA treatment decreased the total symptom score (TSS). The subgroup meta-analysis indicated a decrease of stabbing pain, burning, paraesthesia, and numbness in ALA-treated patients compared to placebo. In addition, both routes of administration, intravenous and oral, demonstrated the efficacy to reduce TSS. Therefore, ALA should be used to treat diabetic polyneuropathy pain symptoms. However, the standardization of treatment time and the dose may advance for the approval of ALA for clinical use in diabetic polyneuroneuropathy.
Learn More >The experimental investigations on the pathogenesis of remifentanil-induced hyperalgesia (RIH) have been primarily conducted, but the effective treatment of RIH remains unclear. Recent reports highlight the necessity of ionotropic glutamate receptors in oxidative damage in spinal nociceptive transduction. Artesunate, the 1-line anti-malaria drug, has been identified to be valid in removing superoxide in several pathological conditions. This study evaluated whether artesunate inhibits RIH via regulating metabotropic glutamate receptor 5 (mGluR5) and mitochondrial antioxidant enzyme peroxiredoxin-3 in rats. Artesunate was injected intrathecally 10 minutes before intravenous infusion of remifentanil (1μg·kg·minfor 60 minutes) in rats. The antinociception of artesunate was verified by assessment of paw withdrawal mechanical threshold and paw withdrawal thermal latency. Spinal mGluR5 expression and peroxiredoxin-3 hyperacetylation were examined. Also, both the mGluR5 agonist DHPG and antagonist MPEP were utilized to explore the involvement of mGluR5 in the anti-hyperalgesic property of artesunate. Here, we found that artesunate (10μg and 100μg but not 1μg) prevented RIH in a dose-dependent manner. Artesunate reduced remifentanil-related spinal over-expression of mGluR5 gene and protein, and hyperacetylation of peroxiredoxin-3. Intrathecal application of MPEP (10nmol and 100nmol but not 1nmol) inhibited behavioral RIH and peroxiredoxin-3 acetylation. Moreover, hyperalgesia and peroxiredoxin-3 hyperacetylation were attenuated after the combination of artesunate (1μg) and MPEP (1nmol). Additionally, artesunate treatment reversed acute pain and peroxiredoxin-3 hyperacetylation following spinal exposure to DHPG. In conclusion, intrathecal injection of artesunate impairs RIH by down-regulating spinal mGluR5 expression and peroxiredoxin-3 hyperacetylation-mediated oxidative stress in rats.
Learn More >To appraise the quality of low back pain (LBP) clinical practice guidelines (CPG) that include interventional management recommendations, and to associate their quality with characteristics including publication year and creating organization.
Learn More >Irritable bowel syndrome (IBS) is a functional gut disorder with multi-factorial pathophysiology that causes recurring pain or discomfort in the abdomen, as well as altered bowel habits. Montelukast, a well-known cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is widely used for the anti-inflammatory management of asthma. The present study aimed to evaluate the effects of pharmacological inhibition of CysLT1R on acetic acid-induced diarrhea-predominant IBS (D-IBS) in rats. Behavioral pain responses to noxious mechanical stimulation were decreased in the montelukast-treated rats as compared to the model animals following colorectal distension (CRD)-induced visceral hypersensitivity. Stool frequency decreased dose-dependently by montelukast in IBS rats exposed to restraint stress. A significantly shorter immobility time was also observed in IBS rats who received montelukast vs IBS group in the forced swimming test (depression-like behavior). Furthermore, there were significant decreases in the NF-κB protein expression, inflammatory cytokine (TNF-α, and IL-1ß) levels, and histopathological inflammatory injuries concomitant with increased anti-inflammatory cytokine, IL-10, in montelukast-treated rats compared with the IBS group. Cysteinyl leukotriene production and CysLT1R mRNA expression showed no remarkable differences among the experimental groups. The present results suggest the possible beneficial effects of montelukast in the management of D-IBS symptoms. The molecular mechanism underlying such effects, at least to some extent, might be through modulating CysLT1R-mediated NF-κB signaling. Yet, more studies are required to demonstrate the clinical potential of this drug for IBS therapy.
Learn More >Visual aura (VA) presents in 98% of cases of migraine with aura. However, data on its prevalence and impact in individuals with migraine and probable migraine (PM) are limited. Data from the nation-wide, population-based Circannual Change in Headache and Sleep Study were collected. Participants with VA rating scale scores ≥ 3 were classified as having VA. Of 3,030 participants, 170 (5.6%) and 337 (11.1%) had migraine and PM, respectively; VA prevalence did not differ between these cohorts (29.4% [50/170] vs. 24.3% [82/337], p = 0.219). Participants with migraine with VA had a higher headache frequency per month (4.0 [2.0-10.0] vs. 2.0 [1.0-4.8], p = 0.014) and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score; 3.0 [1.0-8.0] vs. 2.0 [0.0-4.8], p = 0.046) than those without VA. Participants with PM with VA had a higher headache frequency per month (2.0 [2.0-8.0] vs. 2.0 [0.6-4.0], p = 0.001), greater disability (Migraine Disability Assessment score; 10.0 [5.0-26.3] vs. 5.0 [2.0-12.0], p < 0.001), and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score, 2.5 [0.0-6.0] vs. 0.0 [0.0-3.0], p < 0.001) than those without VA. VA prevalence was similar between migraine and PM. Some symptoms were more severe in the presence of VA.
Learn More >Cannabinoids are emerging as an alternative pain management option, preliminarily supported by preclinical and clinical studies. Unwanted side effects from oral or inhaled cannabinoids remain, however, a major barrier to widespread use. Peripherally acting cannabinoids (eg, topically applied) may circumvent these side effects while providing localized pain management.
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