Non-invasive dural stimulation in mice: A novel preclinical model of migraine

Burgos-Vega, Carolina C.; Quigley, Lilyana; Trevisan, Gabriela; Yan, Flora; Asiedu, Marina N.; Jacobs, Blaine A.; Motina, Marina; Safdar, Nida; Yousuf, Hayyan; Avona, Amanda; Price, Theodore J.; Dussor, Gregory

doi:10.1177/0333102418779557

Cited by 76 publications

(90 citation statements)

References 38 publications

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“…Similar findings in 2 outbred species suggest that these femalespecific responses to dural CGRP are not a peculiarity of mice and are not an artifact of genetic manipulation, increasing confidence that these data may translate to other species. The acute responses of both males and females to dural IL-6 show that overall noxious responses to dural stimulation occur in males (see also Burgos-Vega et al, 2019), but that female-specific responses only occur with certain stimuli. We have also shown previously that priming to dural pH 7.0 occurs in both males and females when the primed state is initiated by IL-6 (Burgos-Vega et al, 2016), demonstrating that priming following dural stimulation is not female-specific.…”

Section: Discussionmentioning

confidence: 94%

Dural Calcitonin Gene-Related Peptide Produces Female-Specific Responses in Rodent Migraine Models

et al. 2019

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Migraine is the second leading cause for disability worldwide and the most common neurological disorder. It is also three times more common in women; reasons for this sex difference are not known. Using preclinical behavioral models of migraine, we show that application of calcitonin gene-related peptide (CGRP) to the rat dura mater produces cutaneous periorbital hypersensitivity. Surprisingly, this response was observed only in females; dural CGRP at doses from 1 pg to 3.8 g produce no responses in males. In females, dural CGRP causes priming to a pH 7.0 solution after animals recover from the initial CGRP-induced allodynia. Dural application of interleukin-6 causes acute responses in males and females but only causes priming to subthreshold dural CGRP (0.1 pg) in females. Intracisternal application of BDNF also causes similar acute hypersensitivity responses in males and females but only priming to subthreshold dural CGRP (0.1 pg) in females. Females were additionally primed to a subthreshold dose of the NO-donor sodium nitroprusside (0.1 mg/kg) following dural CGRP. Finally, the sexually dimorphic responses to dural CGRP were not specific to rats as similar female-specific hypersensitivity responses were seen in mice, where increased grimace responses were also observed. These data are the first to demonstrate that CGRP-induced headache-like behavioral responses at doses up to 3.8 g are female-specific both acutely and following central and peripheral priming. These data further implicate dural CGRP signaling in the pathophysiology of migraine and propose a model where dural CGRP-based mechanisms contribute to the sexual disparity of this female-biased disorder.Calcitonin gene-related peptide (CGRP) has long been implicated in the pathophysiology of migraine, and CGRP-based therapeutics are efficacious for the treatment of migraine in humans. However, the location of action for CGRP in migraine remains unclear. We show here that application of CGRP to the cranial meninges causes behavioral responses consistent with headache in preclinical rodent models. Surprisingly, however, these responses are only observed in females. Acute responses to meningeal CGRP are female-specific and sensitization to CGRP after two distinct stimuli are also female-specific. These data implicate the dura mater as a primary location of action for CGRP in migraine and suggest that female-specific mechanisms downstream of CGRP receptor activation contribute to the higher prevalence of migraine in women.

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Section: Discussionmentioning

confidence: 94%

Dural Calcitonin Gene-Related Peptide Produces Female-Specific Responses in Rodent Migraine Models

et al. 2019

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“…Vehicle‐treated Townes SS mice displayed fewer null responses and more noxious responses to periorbital mechanical stimulation than B6;129 mice (Fig C). In mice, the sensitivity of this region is assessed when studying headache/migraine pain (Burgos‐Vega et al , ), another symptom commonly reported by individuals with SCD (Vgontzas et al , ). Treatment with 30 mg/kg gabapentin had no effect on either B6;129 or Townes SS mice facial hypersensitivity.…”

Section: Resultsmentioning

confidence: 99%

“…Calibrated von Frey filaments were also used to assess facial sensitivity to punctate mechanical stimulation as previously described (Burgos‐Vega et al , ). Animals habituated to testing chambers (acrylic cups, 6·5 cm diameter × 7·0 cm height) for 2 h on each day of the 2 days prior to testing.…”

Section: Methodsmentioning

confidence: 99%

Gabapentin alleviates chronic spontaneous pain and acute hypoxia‐related pain in a mouse model of sickle cell disease

et al. 2019

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Summary Pain is the main complication of sickle cell disease (SCD). Individuals with SCD experience acute pain episodes and chronic daily pain, both of which are managed with opioids. Opioids have deleterious side effects and use‐associated stigma that make them less than ideal for SCD pain management. After recognizing the neuropathic qualities of SCD pain, clinically‐approved therapies for neuropathic pain, including gabapentin, now present unique non‐opioid based therapies for SCD pain management. These experiments explored the efficacy of gabapentin in relieving evoked and spontaneous chronic pain, and hypoxia/reoxygenation (H/R)‐induced acute pain in mouse models of SCD. When administered following H/R, a single dose of gabapentin alleviated mechanical hypersensitivity in SCD mice by decreasing peripheral fibre activity. Gabapentin treatment also alleviated spontaneous ongoing pain in SCD mice. Longitudinal daily administration of gabapentin failed to alleviate H/R‐induced pain or chronic evoked mechanical, cold or deep tissue hypersensitivity in SCD mice. Consistent with this observation, voltage‐gated calcium channel (VGCC) α2δ1 subunit expression was similar in sciatic nerve, dorsal root ganglia and lumbar spinal cord tissue from SCD and control mice. Based on these data, gabapentin may be an effective opioid alternative for the treatment of chronic spontaneous and acute H/R pain in SCD.

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“…For periorbital testing, mice were tested as described by [9]. Briefly, each mouse was acclimated to its own polycoated paper cup (Choice 4 oz.…”

Section: Periorbital and Plantar Tactile Sensitivitymentioning

confidence: 99%

Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles

Wattiez

Castonguay

Gaul

et al. 2020

Preprint

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Chronic complications of traumatic brain injury (TBI) represent one of the greatest financial burdens and sources of suffering in society today. A substantial number of these patients suffer from post-traumatic headache (PTH), which is typically associated with tactile allodynia.Unfortunately, this phenomenon has been under-studied, in large part due to the lack of wellcharacterized laboratory animal models. We have addressed this gap in the field by characterizing the tactile sensory profile of two non-penetrating models of PTH. We show that multifactorial TBI, consisting of aspects of impact, acceleration/deceleration, and blast wave exposure, produces long term tactile hypersensitivity and central sensitization, phenotypes reminiscent of PTH in patients, in both cephalic and extracephalic regions. By contrast, closed head injury induces only transient cephalic tactile hypersensitivity, with no extracephalic consequences. Both models show more severe phenotype with repetitive daily injury for three days, compared to either one or three successive injuries in a single day, providing new insight into patterns of injury that may place patients at greater risk of developing PTH. Importantly, even after recovery from transient cephalic tactile hypersensitivity, mice subjected to closed head injury had persistent hypersensitivity to established migraine triggers, including calcitonin gene-related peptide (CGRP) and sodium nitroprusside, a nitric oxide donor. Our results offer new tools for studying PTH, as well as preclinical support for a pathophysiologic role of CGRP in this condition. SummaryTwo models of post-traumatic headache after traumatic brain injury provide novel laboratory tools and insights in relative risks of injury and therapeutic opportunities.

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Non-invasive dural stimulation in mice: A novel preclinical model of migraine

Cited by 76 publications

References 38 publications

Dural Calcitonin Gene-Related Peptide Produces Female-Specific Responses in Rodent Migraine Models

Dural Calcitonin Gene-Related Peptide Produces Female-Specific Responses in Rodent Migraine Models

Gabapentin alleviates chronic spontaneous pain and acute hypoxia‐related pain in a mouse model of sickle cell disease

Multifactorial and closed head impact traumatic brain injuries cause distinct tactile hypersensitivity profiles

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