The periaqueductal grey matter modulates trigeminovascular input: a role in migraine?

Knight, Yolande E.; Goadsby, Peter J.

doi:10.1016/s0306-4522(01)00303-7

Cited by 222 publications

(163 citation statements)

References 45 publications

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“…Long-term potentiation of nociceptive synapses in the trigeminal nucleus caudalis, with or without alterations of descending endogenous pain modulatory pathways, are plausible hypothetical mechanisms for the maintenance of central sensitization of the trigeminovascular system. 1,2,57 There is evidence that Ca V 2.1 channels play an important role in central sensitization in the spinal cord, 25,58 and that Ca V 2.1 channels located in the periaqueductal gray region and in the rostroventromedial medulla play a role in descending inhibitory and facilitatory pathways that regulate trigeminal and spinal pain. 59,60 Moreover, Ca V 2.1 channels are involved in the control of neurotransmitter release from perivascular terminals of meningeal afferents and consequent neurogenic vasodilation.…”

Section: Familial Hemiplegic Migraine Type 1 (Fhm1)mentioning

confidence: 99%

Familial Hemiplegic Migraine

2007

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Summary: Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A and SCNA1A, encoding the pore-forming ␣ 1 subunits of the neuronal voltage-gated Ca 2ϩ channels Ca V 2.1 and Na ϩ channels Na V 1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the ␣ 2 subunit of the Na ϩ , K ϩ adenosinetriphosphatase (ATPase), are responsible for FHM2. This review discusses the functional studies of two FHM1 knockin mice and of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1 FHM3). These studies show the following: (1) FHM1 mutations produce gain-of-function of the Ca V 2.1 channel and, as a consequence, increased Ca V 2.1-dependent neurotransmitter release from cortical neurons and facilitation of in vivo induction and propagation of cortical spreading depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations produce loss-of-function of the ␣ 2 Na ϩ ,K ϩ -ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na V 1.5 (and presumably Na V 1.1) channels. These findings are consistent with the hypothesis that FHM mutations share the ability of rendering the brain more susceptible to CSD by causing either excessive synaptic glutamate release (FHM1) or decreased removal of K ϩ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K ϩ (FHM3). The FHM data support a key role of CSD in migraine pathogenesis and point to cortical hyperexcitability as the basis for vulnerability to CSD and to migraine attacks. Hence, they support novel therapeutic strategies that consider CSD and cortical hyperexcitability as key targets for preventive migraine treatment.

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Section: Familial Hemiplegic Migraine Type 1 (Fhm1)mentioning

confidence: 99%

Familial Hemiplegic Migraine

2007

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“…The results of a positron emission tomography (PET) study in spontaneous attacks of migraine without aura showed that the PAG has a possible functional and active role as an important pain modulatory structure. The specific brainstem loci involved could not be resolved with PET, but the regions activated were the dorsal midbrain close to PAG 9,11 . Raskin et al reported a group of non-migraine patients developing migraine-like headache after implantation of a stimulating electrode into the PAG 9,12 ; Haas et al reported a headache caused by a single lesion of multiple sclerosis in the PAG 13 .…”

Section: Discussionmentioning

confidence: 98%

“…The distribution of pain and the autonomic phenomena suggest involvement of trigemino-vascular pathways [5][6][7][8] . Several studies show that the PAG plays an important role in the modulation of pain in migraine [9][10][11] . The results of a positron emission tomography (PET) study in spontaneous attacks of migraine without aura showed that the PAG has a possible functional and active role as an important pain modulatory structure.…”

Section: Discussionmentioning

confidence: 99%

Trigemino autonomic cephalalgia and Argyll Robertson pupil

Balthazar

França

Castro

et al. 2008

Arq. Neuro-Psiquiatr.

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The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterized by short-lasting pain, often unilateral, with acompanying ipsilateral autonomic features like conjuntival injection, lacrimation, nasal congestion, rhinorrhea, ptosis or eyelid edema 1 . The group comprises episodic and chronic cluster headache, chronic and episodic paroxysmal hemicrania, and SUNCT syndrome. SUNA syndrome (short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms), although not classified as a TAC, also shares some common characteristics with this group and may include the SUNCT definition. Despite their common elements, the TACs differ in response to therapy, frequency and duration of attacks. They must be differentiated from secundary TACs because of the possible serious and treatable underlying causes, like mass lesions, subarachnoid hemorrhage, pathology in the base of the skull and others 2 . TACs are closely associated to pupillary abnormalities because of the common autonomic structures that control pupillary function and play a role in processing pain. Argyll Robertson pupil (ARP) is a rare kind of pupillary disturbance, most commonly seen in neurosyphilis 3 , and its main feature is lack of reaction to light, with reaction to accommodation.We report a patient with ARP and features of a primary headache (classified as probable TAC) and discuss the possible relationship between these two conditions. CASeA 31-year-old female presented with a one-year history of severe pain around her right eye and sometimes orbito-temporal region. Pain was usually described as pressing but sometimes as stabbing or burning. It was always associated with ipsilateral conjuntival injection, lacrimation, ptosis and occasionally, mild right hypoacusia. Painful episodes lasted from a few seconds (when generally were unchained by gaping) to 20 minutes and used to occur once a day, 3 times/week, with visual analogue scale rated as 8. Such attacks were closely related to distressing situations and were prone to begin any time along the day, but never at sleep. There was neither cutaneous trigger nor allodynia. Past medical and familiar history were unremarkable and her physical, neurologic and cephaliatric examination were normal, except by the ARP, with right pupil smaller than left, even out of attacks ( Figure). Routine hematological, inflammatory and blood

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“…During migraine the PAG was shown to be hyperactive in PET studies [8]. The ventrolateral subdivision of the PAG is of particular importance to the trigeminal nociceptive modulation [20].…”

Section: Discussionmentioning

confidence: 99%

Functional imaging of subcortical nociceptive structures in response to treatment of chronic daily headache

2004

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The objective was to provide objective imaging evidence of functional changes in brainstem structures involved in chronic daily headache (CDH). Over time, episodic migraine (EM) patients may develop CDH known as transformed migraine (TM). Using analysis of transverse relaxation rates, R2, R2* and R2' (R2* values are reflective of blood oxygen level dependence; R2' is a measure of non-heme iron in tissues) we have reported activation (hyperoxia) of red nucleus (RN) and substantia nigra (SN) (decreased R2* and R2') in CDH patients studied during headache, and dysfunction of periaqueductal grey (PAG) based on increased iron levels (elevated R2') [1]. We now report a patient with CDH who, upon treatment, reverted to EM, permitting studies when headache free and an objective analysis of treatment response. SP is a female aged 48 years. She presented with daily headaches for 6 months. Episodic headaches, meeting IHS criteria for migraine without aura, began in her 20s. At the time of presentation she was taking 5 tablets of ergotamine tartarate in the form of Ercaf and 6 extra-strength acetaminophen daily. Repeated dosages of intravenous dihydroergotamine for three days during withdrawal of all medications successfully achieved clinical reversion from CDH to EM. She was studied both during CDH and when headache free after reverting to EM, using high-resolution MR techniques to map the transverse relaxation rates R2, R2* and R2' in RN, SN and PAG. For technical reasons, PAG was not imaged during the CDH phase of her illness. During the CDH phase of her illness, respective R2* values were reduced compared to normal in the RN and SN to 30.1 m/s and 31.45 m/s. Similarly, R2' in RN and SN were abnormally low at 6.62 m/s and 6.72 m/s compared to normal. Subsequent headache free studies demonstrated that R2* and R2' in the RN became 40.1 m/s and 15.47 m/s respectively, and in the SN, 40.25 m/s and 15.19 m/s respectively. These values were similar to EM patients and normal controls. The R2' in PAG during EM for this subject was increased at 6.88 m/s but elevated compared to controls. Daily headache in this patient was associated with chronic activation of pain networks that included RN and SN. Resolution of headache was associated with resolution of activation, although there was evidence for persistent PAG dysfunction, as previously reported. To the best of our knowledge, this case represents the first objective correlation of functional changes in brainstem nociceptive networks with clinical features of TM and its response to treatment.

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The periaqueductal grey matter modulates trigeminovascular input: a role in migraine?

Cited by 222 publications

References 45 publications

Familial Hemiplegic Migraine

Familial Hemiplegic Migraine

Trigemino autonomic cephalalgia and Argyll Robertson pupil

Functional imaging of subcortical nociceptive structures in response to treatment of chronic daily headache

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