BACKGROUND: The development and approval of antibodies targeting calcitonin gene-related peptide or its receptor mark a revolutionary era for preventive migraine treatment. Real-world evidence sheds light on rare, stigmatized or overlooked side effects of these drugs. One of these potential side effects is sexual dysfunction.
METHODS: We present two cases of one 42-year-old and one 45-year-old female patient with chronic migraine who both reported sexual dysfunction as a possible side effect of treatment with galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide.
CONCLUSIONS: As calcitonin gene-related peptide is involved in vaginal lubrication as well as genital sensation and swelling, inhibiting the calcitonin gene-related peptide pathway may lead to sexual dysfunction as a potential side effect.
CONCLUSIONS: Sexual dysfunction in female migraine patients might be a rare and overlooked side effect of monoclonal antibodies targeting the calcitonin gene-related peptide pathway. Considering the discomfort and stigma surrounding both migraine and sexual dysfunction, we advocate for an open attitude and awareness among clinicians toward such side effects.

Limited clinical evidence is available regarding the potential effectiveness of anti-CGRP monoclonal antibodies for the preventive treatment of migraine with aura.
This observational study involved a series of migraine patients affected by either migraine with or without aura, who were investigated for any changes in their frequencies and their migraine aura attack characteristics observed during treatment with anti-CGRP Mabs over a 1-year period.
Twelve migraine patients were included, seven of whom were treated with erenumab, 2 with fremanezumab, and 3 with galcanezumab. Clinical data were collected at baseline, which were defined as 3 months prior to the initiation of treatment, and thereafter at each trimester, over the 1-year treatment period. The parameters included the number of headache and migraine days/month, the frequency of aura episodes, the number of days with acute drug intakes/month, and the scores from the migraine disability status scale (MIDAS), and the Headache Impact Test 6 (HIT-6).
Anti-CGRP Mbs antibodies induced significant decreases in mean headache and migraine without aura days per month, the number of days with medication intake, as well as MIDAS and HIT-6 scores (p < 0.0001). In contrast, the anti-CGRP Mab treatment did not appear to impact the frequency of migraine with aura attacks but seemed to reduce both the intensity and the duration of headache phases of migraine aura. Furthermore, some migraine patients referred to having aura attacks without headache over the course of the treatment period.
Based on the above findings, we hypothesize that anti-CGRP Mabs did not influence neuronal and vascular events related to cortical spreading depression (CSD) which is considered the pathophysiological substrate of aura. Conversely, these antibodies are able to counteract, via their peripheral mechanisms of action, the sensitization of the trigemino-vascular pathway which is triggered by CSD. This aforementioned might explain why in our patients, migraine aura attacks remained unchanged in their frequencies, but the headache phases were either reduced or absent.

BACKGROUND: A previously unreported systemic reaction to Galcanezumab (Emgality) is described. Galcanezumab is a humanized monoclonal antibody designed to bind to calcitonin gene-related peptide, a neuropeptide associated with neurogenic inflammation during migraine attacks. Although clinical trials showed that Galcanezumab had few adverse reactions (injection site related erythema, pruritus, and swelling), no systemic drug reactions have been noted.
METHODS: A 50-year-old female with chronic migraine, mast cell disorder, Hashimoto\'s disease, positive antinuclear antibody and positive anti-cyclic citrullinated peptide antibody not on immune modulators received the initial dose of galcanezumab 240 mg after failing multiple migraine treatments. The following day, she developed injection site reaction, malar erythema and flu-like symptoms. Symptoms progressed the second day after injection, and she developed swelling in her lips and throat. Intravenous steroid and antihistamines improved airway symptoms, and the remaining symptoms improved after a course of oral steroids.
CONCLUSIONS: Delayed system allergic reaction to Galcanezumab requiring emergency intervention may occur. A history of autoimmune disorder may be a predisposing factor.

BACKGROUND: Neuroinflammation and maladaptive neuroplasticity play pivotal roles in migraine (MIG), trigeminal autonomic cephalalgias (TAC), and complex regional pain syndrome (CRPS). Notably, CRPS shares connections with calcitonin gene-related peptide (CGRP) in its pathophysiology. This study aims to assess if the documented links between CRPS and MIG/TAC in literature align with clinical phenotypes and disease progressions. This assessment may bolster the hypothesis of shared pathophysiological mechanisms.
METHODS: Patients with CRPS (n = 184) and an age-/gender-matched control group with trauma but without CRPS (n = 148) participated in this case-control study. Participant answered well-established questionnaires for the definition of CRPS symptoms, any headache complaints, headache entity, and clinical management.
RESULTS: Patients with CRPS were significantly more likely to suffer from migraine (OR: 3.23, 95% CI 1.82-5.85), TAC (OR: 8.07, 95% CI 1.33-154.79), or non-classified headaches (OR: 3.68, 95% CI 1.88-7.49) compared to the control group. Patients with MIG/TAC developed CRPS earlier in life (37.2 ± 11.1 vs 46.8 ± 13.5 years), had more often a central CRPS phenotype (60.6% vs. 37.0% overall) and were three times more likely to report allodynia compared to CRPS patients with other types of headaches. Additionally, these patients experienced higher pain levels and more severe CRPS, which intensified with an increasing number of headache days. Patients receiving monoclonal antibody treatment targeting the CGRP pathway for headaches reported positive effects on CRPS symptoms.
CONCLUSIONS: This study identified clinically relevant associations of MIG/TAC and CRPS not explained by chance. Further longitudinal investigations exploring potentially mutual pathomechanisms may improve the clinical management of both CRPS and primary headache disorders.
BACKGROUND: German Clinical Trials Register (DRKS00022961).

BACKGROUND: Glomus Tumor (GT) are benign neoplasms that originate from mesenchymal cells. It presents as tenderness and cold allodynia in the digits, especially in the subungual region. There are a few studies that investigated the mechanism of pain.
OBJECTIVE: To analyze the clinical-pathologic characteristics of GT and to identify the expression of IL-1β, IL-6, and CGRP in it, further, to explore the possible mechanism of pain.
METHODS: The clinical and pathological data of 60 GT patients were retrospectively analyzed. Tissue microarrays and immunohistochemistry were used to measure the expression of IL-1β, IL-6 and CGRP.
RESULTS: GT is more common in females and the ratio of male to was near to 1:2, mostly in middle-aged people. It often occurs in fingertips, especially the thumbs. Patients often present with spontaneous pain, tenderness, and cold hypersensitivity. Both the two pain mediators IL-1β and IL-6 were highly expressed in GT cells of patients with and without cold hypersensitivity. While CGRP was not expressed in GT.
CONCLUSIONS: Low sample size and further research is needed to explore the specific mechanism.
CONCLUSIONS: IL-1β and IL-6 were highly expressed in GT cells, suggesting that IL-1β and IL-6 have certain nociceptive roles in GT. In the 4 patients with cold intolerance, the intensity of IL-1β and IL-6 staining was also strong, suggesting that they may not play a role in the cold hypersensitivity. However, since there are only 4 patients with cold intolerance, it\'s necessary to conduct further in-depth research using a larger sample size. The specific role of CGRP in GT has not been found yet.