Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated rats: implications for chronic migraine

Akçali, Didem Tuba; Belen, Ahmet Deniz; Babacan, Avni; Bolay, Hayrünnisa

doi:10.3906/sag-1602-86

Cited by 13 publications

(6 citation statements)

References 38 publications

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“…Thermal allodynia can be measured with different methodologies including the Hargreaves' test (73), based on applying a heat stimulus to the hind paws or tail of the animal to measure their withdrawal latency; and the acetone evaporation test, which measures the aversive behaviors elicited by evaporative cooling both in cephalic or extracephalic regions (74). These tests have been used in preclinical models of migraine, where the administration of nitroglycerin and algogenic substances have shown to increase thermal allodynia (67,68), and the nasocilary nerve ligation to increase sensitization to acetone evaporation (75).…”

Section: Use Of Allodynia As a Readout Of Migraine-like Pain In Preclinical Modelsmentioning

confidence: 99%

Cutaneous Allodynia in Migraine: A Narrative Review

et al. 2022

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ObjectiveIn the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine.BackgroundCA is regarded as the perception of pain in response to non-noxious skin stimulation. The number of research studies relating to CA and migraine has increased strikingly over the last few decades. Therefore, the clinician treating migraine patients must recognize this common symptom and have up-to-date knowledge of its importance from the pathophysiological, diagnostic, prognostic and therapeutic point of view.MethodsWe performed a comprehensive narrative review to analyze existing literature regarding CA in migraine, with a special focus on epidemiology, pathophysiology, assessment methods, risk for chronification, diagnosis and management. PubMed and the Cochrane databases were used for the literature search.ResultsThe prevalence of CA in patients with migraine is approximately 60%. The mechanisms underlying CA in migraine are not completely clarified but include a sensitization phenomenon at different levels of the trigemino-talamo-cortical nociceptive pathway and dysfunction of brainstem and cortical areas that modulate thalamocortical inputs. The gold standard for the assessment of CA is quantitative sensory testing (QST), but the validated Allodynia 12-item questionnaire is preferred in clinical setting. The presence of CA is associated with an increased risk of migraine chronification and has therapeutic implications.ConclusionsCA is a marker of central sensitization in patients with migraine that has been associated with an increased risk of chronification and may influence therapeutic decisions.

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Section: Use Of Allodynia As a Readout Of Migraine-like Pain In Preclinical Modelsmentioning

confidence: 99%

Cutaneous Allodynia in Migraine: A Narrative Review

et al. 2022

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“…Stimulation with the paintbrush is repeated three times, at least 3 min in-between, and the average of three scores are calculated. Brush allodynia is used in neuropathic pain models, and chronic migraine model developed by nasociliary nerve ligation [46].…”

Section: Sensory-discriminative Aspectsmentioning

confidence: 99%

“…Akcali et al provided a chronic migraine animal model with nasociliary nerve ligation in rats and provoked lateralized headache attack by NTG. In the study, NTG administration increased acetone sensitivity in the forehead only in nasociliary nerve ligated side [46]. In a NTG-induced mouse model of chronic migraine, the duration of withdrawal responses to acetone in the facial region were significantly increased in mice treated with NTG compared to control [52].…”

Section: Sensory-discriminative Aspectsmentioning

confidence: 99%

Behavioral and cognitive animal models in headache research

et al. 2019

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Animal models have provided a growing body of information about the pathophysiology of headaches and novel therapeutic targets. In recent years, experiments in awake animals have gained attention as more relevant headache models. Pain can be assessed in animals using behavioral alterations, which includes sensory-discriminative, affective-emotional and cognitive aspects. Spontaneous behavioral alterations such as increased grooming, freezing, eye blinking, wet dog shake and head shake and decreased locomotion, rearing, food or water consumption observed during pain episodes are oftentimes easy to translate into clinical outcomes, but are giving little information about the localization and modality of the pain. Evoked pain response such as tactile and thermal hypersensitivity measures are less translatable but gives more insight into mechanisms of action. Mechanical allodynia is usually assessed with von Frey monofilaments and dynamic aesthesiometer, and thermal allodynia can be evaluated with acetone evaporation test and Hargreaves’ test in animal models. Anxiety and depression are the most frequent comorbid diseases in headache disorders. Anxiety-like behaviors are evaluated with the open-field, elevated plus-maze or light/dark box tests. Interpretation of the latter test is challenging in migraine models, as presence of photophobia or photosensitivity can also be measured in light/dark boxes. Depressive behavior is assessed with the forced-swim or tail suspension tests. The majority of headache patients complain of cognitive symptoms and migraine is associated with poor cognitive performance in clinic-based studies. Cluster headache and tension type headache patients also exhibit a reversible cognitive dysfunction during the headache attacks. However, only a limited number of animal studies have investigated cognitive aspects of headache disorders, which remains a relatively unexplored aspect of these pathologies. Thus, the headache field has an excellent and growing selection of model systems that are likely to yield exciting advances in the future.

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“…Using the Hargreaves assay, acute nitroglycerin [84] and chronic administration of algogenic substances increased thermal sensitivity [83, 165]. Furthermore, a different model of chronic migraine, nasocilary nerve ligation in rats, exhibits a lateralized sensitization to acetone following nitroglycerin in the forehead ipsilateral of nerve ligation [173]. One important differentiation is that behavioral studies have also shown differential response to mechanical and thermal allodynia, highlighting the complexity of trigeminal pain processing.…”

Section: Experimental Readouts: Behavioral Assaysmentioning

confidence: 99%

Animal models of migraine and experimental techniques used to examine trigeminal sensory processing

et al. 2019

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BackgroundMigraine is a common debilitating condition whose main attributes are severe recurrent headaches with accompanying sensitivity to light and sound, nausea and vomiting. Migraine-related pain is a major cause of its accompanying disability and can encumber almost every aspect of daily life.Main bodyAdvancements in our understanding of the neurobiology of migraine headache have come in large from basic science research utilizing small animal models of migraine-related pain. In this current review, we aim to describe several commonly utilized preclinical models of migraine. We will discuss the diverse array of methodologies for triggering and measuring migraine-related pain phenotypes and highlight briefly specific advantages and limitations therein. Finally, we will address potential future challenges/opportunities to refine existing and develop novel preclinical models of migraine that move beyond migraine-related pain and expand into alternate migraine-related phenotypes.ConclusionSeveral well validated animal models of pain relevant for headache exist, the researcher should consider the advantages and limitations of each model before selecting the most appropriate to answer the specific research question. Further, we should continually strive to refine existing and generate new animal and non-animal models that have the ability to advance our understanding of head pain as well as non-pain symptoms of primary headache disorders.

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Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated rats: implications for chronic migraine

Cited by 13 publications

References 38 publications

Cutaneous Allodynia in Migraine: A Narrative Review

Cutaneous Allodynia in Migraine: A Narrative Review

Behavioral and cognitive animal models in headache research

Animal models of migraine and experimental techniques used to examine trigeminal sensory processing

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