Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia.

Migraine is one of the most common pain disorders and causes disability in millions of people every year. Delta opioid receptors (DOR) have been identified as a novel therapeutic target for migraine and other headache disorders. DORs are present in both peripheral and central regions and it is unclear which receptor populations regulate migraine-associated effects.

Delta opioid receptor regulation of calcitonin gene-related peptide dynamics in the trigeminal complex.

Migraine is highly prevalent and is the sixth leading cause worldwide for years lost to disability. Therapeutic options specifically targeting migraine are limited, and delta opioid receptor (DOP) agonists were recently identified as a promising pharmacotherapy. The mechanisms by which DOPs regulate migraine are currently unclear.

Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia.

Delta opioid receptor (DOR) agonists have been identified as a promising novel therapy for headache disorders. DORs are broadly expressed in several peripheral and central regions important for pain processing and mood regulation; and it is unclear which receptors regulate headache associated symptoms. In a model of chronic migraine-associated pain using the human migraine trigger, nitroglycerin, we observed increased expression of DOR in cortex, hippocampus, and striatum; suggesting a role for these forebrain regions in the regulation of migraine.

Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus Accumbens.

The benefits of opioid-based treatments to mitigate chronic pain can be hindered by the side effects of opioid-induced hyperalgesia (OIH) that can lead to higher consumption and risk of addiction. The present study advances the understanding of the molecular mechanisms associated with OIH by comparing mice presenting OIH symptoms in response to chronic morphine exposure (OIH treatment) relative to control mice (CON treatment). Using RNA-Seq profiles, gene networks were inferred in the trigeminal ganglia (TG), a central nervous system region associated with pain signaling, and in the nucleus accumbens (NAc), a region associated with reward dependency.

Gene Network Dysregulation in the Trigeminal Ganglia and Nucleus Accumbens of a Model of Chronic Migraine-Associated Hyperalgesia.

The pharmacological agent nitroglycerin (NTG) elicits hyperalgesia and allodynia in mice. This model has been used to study the neurological disorder of trigeminovascular pain or migraine, a debilitating form of hyperalgesia. The present study validates hyperalgesia in an established mouse model of chronic migraine triggered by NTG and advances the understanding of the associated molecular mechanisms.

Delta opioid receptor agonists are effective for multiple types of headache disorders.

Headaches are highly disabling and are among the most common neurological disorders worldwide. Despite the high prevalence of headache, therapeutic options are limited. We recently identified the delta opioid receptor (DOR) as an emerging therapeutic target for migraine.

The development of a mouse model of mTBI-induced post-traumatic migraine, and identification of the delta opioid receptor as a novel therapeutic target.

Background: Post-traumatic headache is the most common and long-lasting impairment observed following mild traumatic brain injury, and frequently has migraine-like characteristics. The mechanisms underlying progression from mild traumatic brain injury to post-traumatic headache are not fully understood. The aim of this study was to develop a mouse model of post-traumatic headache and identify mechanisms and novel targets associated with this disorder.

Soluble guanylyl cyclase is a critical regulator of migraine-associated pain.

Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology.

Animal Model of Chronic Migraine-Associated Pain.

Migraine is a debilitating condition that affects hundreds of millions of people worldwide. A subset of these patients experience chronic migraine, resulting in long-term disability and a severely lowered quality of life. The development of novel migraine therapies has been slow, partially due to the small number of predictive animal models.

From blast to bench: A translational mini-review of posttraumatic headache.

Current events within the military and professional sports have resulted in an increased recognition of the long-term and debilitating consequences of traumatic brain injury. Mild traumatic brain injury accounts for the majority of head injuries, and posttraumatic headache is the most common adverse effect. It is estimated that between 30% to 90% of traumatic brain injuries result in posttraumatic headache, and for a significant number of people this headache disorder can continue for up to and over a year post injury.