Nociception Coma Scale with personalized painful stimulation versus standard stimulus in non-communicative patients with disorders of consciousness.

INTRODUCTION: Persons with disorders of consciousness (DoC) may perceive pain without being able to communicate their discomfort. Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in coma survivors with DoC. OBJECTIVE: Aim of the present study was to compare, in non-communicative patients with DoC, NCS-R scores obtained with the standard pressure on fingernail bed (standard stimulus, SS) versus other personalized painful stimuli (PS), to verify possible correlations between NCS-R and Coma Recovery Scale-Revised (CRS-R). MATERIALS AND METHODS: Twenty-one patients with DoC were included in the study. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). Statistical analysis was performed with the nonparametric Wilcoxon test for comparison of both total NCS-R-SS and NCS-R-PS scores. RESULTS: NCS-R at admission showed that 9 of 21 patients (42.8%) had higher scores in response to personalized stimulus compared to standard stimulus. Significant correlation with CRS-R were found for both NCS-R-SS (R = 0.701, p = .008) and NCS-R-PS (R = 0.564, p = .045). Discussion: The preliminary results obtained in the present study suggest that NCS-R-PS may disclose pain perception in a larger number of non-communicative patients with DoC, compared to NCS-R-SS.

Effects of CGRP receptor antagonism in nitroglycerin-induced hyperalgesia.

BACKGROUND: The release of calcitonin gene-related peptide (CGRP) from trigeminal nerves plays a central role in the pathophysiology of migraine and clinical evidence shows an antimigraine effect for CGRP receptor antagonists. Systemic administration of nitroglycerin (NTG), a nitrovasodilator, consistently provokes spontaneous-like migraine attacks in migraine sufferers; in the rat, systemic NTG induces a condition of hyperalgesia, probably through the activation of cerebral/spinal structures involved in nociceptive transmission. AIM: The aim of this article is to test the analgesic effect of the CGRP receptor antagonist MK-8825 in two animal models of pain that may be relevant for migraine: the tail flick test and the formalin test performed during NTG-induced hyperalgesia. RESULTS: MK-8825 showed analgesic activity when administered alone at both the tail flick test and the formalin test. Furthermore, the CGRP antagonist proved effective in counteracting NTG-induced hyperalgesia in both tests. MK-8825 indeed reduced the nociceptive behavior when administered either simultaneously or prior to (30-60 minutes before) NTG. CONCLUSION: These data suggest that MK-8825 may represent a potential therapeutic tool for the treatment of migraine.

Pathways to the best fit of triptans for migraine patients.

Variability in drug response is a major barrier to the successful treatment of migraine, and most treatments are only optimal in a subset of patients. Although triptans provide the best therapeutic option for the treatment of acute migraine, it has not previously been possible to predict how well patients will respond to a specific triptan or whether they will experience unpleasant adverse events. Hence, it has been difficult for physicians to match individual patients with the most suitable agent to treat their migraine pain. Intrapatient variability has been associated with polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters and drug targets. Pharmacogenetics provides the possibility of tailoring the therapeutic approach to individual patients, in order to maximize treatment efficacy while minimizing the potential for unwanted side-effects. This review demonstrates how almotriptan may overcome genetically determined responses by utilizing diverse metabolic pathways to provide therapeutic benefit to many migraineurs.

The effects on the central nervous system of nitroglycerin--putative mechanisms and mediators.

Nitroglycerin is an organic nitrate that has been used as a vasodilator in the treatment of cardiac diseases for over a century. Only recently it has been demonstrated that the vasodilator effect of this drug depends upon the formation of nitric oxide in the blood vessel wall. However, clinical and research data gathered during the last decades have suggested that nitroglycerin possesses, besides its peripheral vasodilator effect, additional, puzzling biological activities. This organic nitrate compound provokes reflex cardiovascular activities via its interaction with the central sympathetic system. Its cerebrovascular effect, on the other hand, is probably mediated by the local release of neuropeptides. The direct application of nitroglycerin onto brain nuclei causes a prompt increase in the neuronal discharge rate. From a neurological point of view, nitroglycerin consistently induces a specific headache attack in patients suffering from migraine. Because of its temporal pattern and clinical characteristics, nitroglycerin-induced headache cannot be solely ascribed to the a drug-induced vasorelaxation. The demonstration that systemic nitroglycerin administration activates a widespread set of vegetative, nociceptive and neuroendocrine structures in the central nervous system seems to further support the occurrence of central mechanisms in the biological activity of nitroglycerin. Double labeling immunocytochemical and neuropharmacological studies have provided information on the putative neurotransmitters and neurochemical mechanisms involved in nitroglycerin-induced neuronal activation.

Early clinical predictive factors during coma recovery.

In severe brain injury patients few studies have examined the role of early clinical factors emerging before recovery of consciousness. Patients suffering from vegetative state and minimally conscious state in fact may need variable periods of time for recovery of the ability to follow commands. In a previous study we retrospectively examined a population of very severe traumatic brain injury patients with coma duration of at least 15 days (prolonged coma), and we found, as significant predictive factors for the final outcome, the time interval from brain injury to the recovery of the following clinical variables: optical fixation, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia during coma recovery were also favourable prognostic factors for the final outcome. In a further study, also as for the neuropsychological recovery, the clinical variable with the best significant predictive value was the interval from head trauma to the recovery of safe oral feeding. In the present study the presence of psychomotor agitation diagnosed by means of LCF (score 4 = confused-agitated) at the admission time in rehabilitation predicted a statistically significant better outcome at the discharge time in comparison with patients without agitation.

Preproenkephalin upregulation in nucleus caudalis: high and low intensity afferent stimulation differentially modulate early and late responses.

Nucleus caudalis expression of preproenkephalin mRNA changes following lesions depleting small-caliber primary afferent fibers and after stimulation of trigeminal afferents at different intensities. Animals treated neonatally with capsaicin display reduced preproenkephalin gene expression in nucleus caudalis neurons. Stimulation of normal animals at low intensities enhances preproenkephalin expression in a bimodal temporal pattern. High intensity stimulation is effective only at later time points in normal animals, but it causes both early and late effects on preproenkephalin expression when applied to animals neonatally lesioned with capsaicin. Transsynaptic regulation of preproenkephalin expression in pain-modulating areas of the nucleus caudalis of the trigeminal nerve thus depends on the specific type of primary afferent input. The rapid responses noted after selective large fiber stimulation appear to be suppressed by coactivation of small caliber fibers. Later responses appear less influenced by the quality of the eliciting afferent stimulus.

mtDNA A3243G MELAS mutation is not associated with multigenerational female migraine.

The authors searched for mitochondrial DNA (mtDNA) A3243G mutation in peripheral blood leukocytes from female migraine patients with pure matrilinear history of migraine along two or three generations. The current study was designed to exclude any male transmission of the disease. The mutation was absent in all patients. We conclude that mtDNA A3243G mutation does not contribute to the pathogenesis of pure matrilinear multigenerational migraine with or without aura.

Use of Bacille Calmette-Guèrin (BCG) in multiple sclerosis.

We studied the effect of Bacille Calmette-Guerin (BCG) vaccine as an immunomodulator in MS. According to the guidelines for clinical trials in MS, a single crossover, MRI-monitored trial was performed in 14 patients with relapsing-remitting MS. After treatment, MRI activity was significantly reduced. No major adverse effects were reported. Adjuvant therapy with BCG vaccine was safe and merits study in MS.

Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion.

Vasoactive neuropeptides, present in unmyelinated C-fibers, can be released from perivascular sensory axons by antidromic stimulation, to mediate vasodilation and extravasation of plasma protein (neurogenic inflammation). In this report, the effects of antidromic trigeminal stimulation on levels of calcitonin gene-related peptide (CGRP) in plasma were examined in the superior sagittal sinus and the effects of drugs that have been shown previously to block extravasation of neurogenic plasma determined. The levels of immunoreactive CGRP in plasma were measured both before and during electrical stimulation of the trigeminal ganglion (0.1-1.0 mA, 5 msec, 5 Hz, 3-5 min), using a highly specific and sensitive immunochemiluminometric assay. Levels of CGRP increased and became maximal within the first minute of stimulation. The increases were detectable at intensities of current as small as 0.1 mA. Peak levels related to the intensity of the stimulus. Samples from femoral arterial blood did not show concomitant increases at 1 min. Pretreatment with dihydroergotamine (DHE) (50 micrograms/kg i.v.) did not change the baseline levels but decreased levels of CGRP during stimulation (0.3 mA), by 55% at 1 min and 50% at 3 min. Sumatriptan (GR43175) (300 micrograms/kg) attenuated the increase by 57% at 3 min (0.1 mA, 5 msec, 5 Hz) but not after 1 min of stimulation, although decreases were observed at the latter time during an individual experiment. Drug-induced attenuation of levels of CGRP in plasma may reflect inhibition of release, to thereby provide evidence to explain blockade of neurogenic extravasation of plasma.

Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation.

We investigated the effects of unilateral electrical trigeminal ganglion stimulation (0.1 or 1.0 mA, 5 Hz, 5 ms, 5 min) on the morphology of blood vessels within the rat dura mater and tongue using light and transmission electron microscopy. Stimulation at both intensities caused changes which were confined to the ipsilateral post-capillary venules except in the tongue where arterioles were affected as well. Changes were more marked after 1.0 mA. Dramatic increases in the numbers of endothelial pinocytotic vesicles were found along the luminal and abluminal surfaces ipsilateral to the stimulation. Tight junctions remained largely intact, except that injected ferritin particles were occasionally trapped inside these junctions. Cytoplasmic microvilli and endothelial blebs were sometimes present as well. Approximately 80% of the examined dural post-capillary venules showed one or more of these endothelial changes. Horseradish peroxidase injected intravenously 5 min prior to stimulation was detected in the extracellular space surrounding dural blood vessels and within pinocytotic vesicles. Ferritin injected similarly, was also localized in post-capillary venule walls, interstitial spaces, intraendothelial vesicles and in vacuoles. Platelet accumulation and aggregation were present in approximately 10% of post-capillary venules in dura and tongue. These changes were associated with mast cell secretion, but neither vascular nor mast cell activation was observed in adult rats in whom C-fibers were destroyed during the neonatal period with capsaicin. The present observations provide morphological evidence which supports findings from previously reported albumin tracer studies suggesting enhanced transport and endothelial activation following electrical stimulation of small caliber afferent fibers.

Trigeminal sensory fiber stimulation induces morphological changes reflecting secretion in rat dura mater mast cells.

Mast cells are involved in allergic reactions, but may also participate in neurogenic inflammation. The morphology of mast cells in rat dura mater and tongue was evaluated by histochemistry, as well as by scanning and transmission electron microscopy following unilateral trigeminal ganglion stimulation (5 min, 5 Hz, 5 ms, and 0.02, 0.1 or 1.0 mA). Mast cells in dura and tongue of normal animals were numerous, perivascular and often in close proximity to nerve fibers. After 5 min of electrical stimulation, mast cells contralateral to the stimulation showed histochemical characteristics of normal peripheral tissue mast cells (Safranin-positive), and by electron microscopy appeared homogeneous with numerous intact electron-dense granules. On the stimulated side, however, the staining characteristics of mast cells showed changes indicating progressive intracellular loss of their granular content. In addition, the total number of stainable mast cells decreased at all three stimulus intensities, but reached significance only at 0.1 and 0.02 mA. Ultrastructural evidence of granule changes consistent with secretion were observed although degranulation was not observed until 20 min after stimulation. There were no mast cell changes after electrical trigeminal stimulation in adult rats treated as neonates with capsaicin to destroy small caliber sensory afferent axons. These results suggest that mast cells may secrete in response to electrical stimulation of trigeminal axons, possibly mediated by antidromic release of neuropeptides, and may participate in the development of neurogenic inflammation.

The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater.

1. We describe the actions of GR43175, a 5-hydroxytryptamine1 (5-HT1)-like receptor agonist, on neurogenically-mediated plasma protein extravasation within an important pain-sensitive intracranial tissue, the dura mater. 2. GR43175 markedly attenuated extravasation of 125I-albumin from blood vessels within ipsilateral dura mater when administered to rats (100 micrograms kg-1) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5 Hz, 5 ms, 5 min); the ratio (stimulated/unstimulated sides) decreased from 1.81 to 1.23, P less than 0.005). 3. GR43175 (100 micrograms kg-1, i.v., rats; 30 micrograms kg-1, guinea-pigs) decreased the leakage of radiolabelled albumin from 163% to 119% (P less than 0.005, guinea-pig) or from 174 to 118% (P less than 0.05, rat) above vehicle-treated controls when injected ten minutes before systemic capsaicin treatment (0.5 or 1 mumol kg-1, i.v.). 4. GR43175 (30-300 micrograms kg-1) did not block plasma protein extravasation within extracranial tissues of rats and guinea-pigs innervated by the trigeminal nerve (conjunctiva, eyelid and lip). 5. The protein leakage which followed the i.v. administration of 5-HT (1 mumol kg-1) or neuropeptides which mediate neurogenic plasma extravasation, substance P (0.3 nmol kg-1 or 1 nmol kg-1) and neurokinin A (1 nmol kg-1), was not blocked by GR43175 (100, 300 micrograms kg-1) despite the presence of leakage in amounts equivalent to that following neurogenic stimulation. 6. GR43175 (100 micrograms kg-1) decreased bradykinin (10 mumol kg-1)-induced extravasation from 142 to 115% above vehicle-treated animals (P less than 0.05). 7. These results demonstrate an important action of GR43175 on neurogenic mechanisms in dural blood vessels. Since the ergot alkaloids possess a similar profile of drug activity, it is suggested that drugs useful in the treatment of acute vascular headaches may share a similar mechanism of action.

Further characterization of the putative 5-HT receptor which mediates blockade of neurogenic plasma extravasation in rat dura mater.

1. We describe the effects of pretreatment with 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on neurogenically-mediated plasma protein extravasation ([125I]-albumin) in rat dura mater and in extracranial tissues (temporalis muscle fascia, conjunctiva, eyelid and lip) induced by electrical stimulation of the right trigeminal ganglion. 2. Leakage of [125I]-bovine serum albumin from blood vessels in dura mater following high intensity stimulation (1.2 mA, 5 ms, 5 Hz for 5 min) was significantly reduced by the intravenous administration of drugs active at 5-HT receptors with some selectivity for the 5-HT1 receptor subtypes: 5-carboxamidotryptamine (5-CT) (threshold dose, 1 ng kg-1); 5-benzyloxytryptamine (5-BT) (10, 30 or 100 micrograms kg-1); 8-hydroxydipropylaminotetralin (8-OH-DPAT) (300 micrograms kg-1); and as previously reported, sumatriptan (100 micrograms kg-1), dihydroergotamine (DHE) (50 micrograms kg-1); ergotamine tartrate (100 micrograms kg-1) and chronically administered methysergide (1 mg kg-1). 3. The putative 5-HT receptor antagonist, metergoline 100 micrograms kg-1, inhibited partially the effect of sumatriptan in dura mater providing additional evidence for a 5-HT1 receptor subtype-mediated mechanism, although it was not effective against 5-CT (1 ng kg-1). Methiothepin (300 micrograms kg-1) did not affect the response to sumatriptan. When administered at high concentrations (1 mg kg-1) methiothepin and metergoline decreased plasma protein extravasation in rat dura mater. 4. Pretreatment with the 5-HT2 receptor antagonists pizotifen, 300pugkg 1, or ketanserin, 300,ugkg ', or the 5-HT3 receptor antagonists MDL 72222, 300,ugkg-1, or ICS 205-930, 300pgkg-1, did not affect plasma protein leakage following electrical trigeminal stimulation. Blockade by sumatriptan of plasma protein extravasation was not inhibited by pizotifen (300,ug kg-1) or MDL 72222 (300pg kg- '). 5. The 5-HT receptor(s) mediating this response were present only on intracranial tissues innervated by the trigeminal nerve; plasma protein extravasation in extracranial tissues was not blocked by pretreatment with the equivalent or higher concentrations of the above drugs following low intensity trigeminal stimulation (0.1 mA, 5 ms, 5 Hz). 6. The putative 5-HT receptor(s) mediating this response were not present on sympathetic fibres innervating dura mater since unilateral removal of the superior cervical ganglion did not prevent the development of plasma protein extravasation nor did it affect the blockade by sumatriptan IOOpug kg- '. 7. The above pharmacological data suggest that intracranial vessels possess 5-HT receptor(s) which are coupled to inhibition of neurogenically-mediated plasma protein extravasation. These receptors cannot be detected on extracranial cephalic blood vessels innervated by the trigeminal nerve, although available evidence strongly suggests that the 5-HT receptors reside on perivascular trigeminal nerve fibres. The rank order of effective doses (threshold concentrations; 5-CT < 5-BT < DHE < sumatriptan < 8-OHDPAT) is most consistent with a 5-HTlB- or 5-HTlD-mediated response, among the known 5-HT1 family of receptors. However, the lack of effect of methiothepin against the actions of sumatriptan, or metergoline against the effects of 5-CT suggest important differences and the possibility that a previously unrecognized 5-HT receptor(s) is involved in this response.

Preproenkephalin mRNA expression in nucleus caudalis neurons is enhanced by trigeminal stimulation.

Electrical stimulation of trigeminal afferents increases expression of preproenkephalin mRNA in neurons of laminae I and II of the trigeminal nucleus caudalis in animals sacrificed 6 hours after the end of stimulation. More neurons express, and positive cells express at higher levels. These neurons thus express the mRNA corresponding to a major pain-modulating neurotransmitter gene with significant input-related plasticity.

Jun B, c-jun, jun D and c-fos mRNAs in nucleus caudalis neurons: rapid selective enhancement by afferent stimulation.

In situ hybridization using cDNAs complementary to specific regions of the mRNAs encoding 3 members of the jun transcription factor gene family and c-fos reveals modest levels of hybridization over superficial laminae of the nucleus caudalis of the spinal tract of the trigeminal in sections taken from unstimulated brains. Jun B expression is markedly and rapidly enhanced ipsilateral to electrical stimulation of the trigeminal ganglion. C-fos mRNA levels also show changes, especially after higher intensity stimulation. Smaller alterations in c-jun (jun A) and jun D do not reach statistical significance. In each instance of altered expression, more neurons express hybridization densities above background levels after stimulation. Parallels between these alterations and changes in the expression of preproenkephalin in these same neuronal populations are discussed.

5-Hydroxytryptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation.

Antidromic stimulation of small caliber trigeminal axons causes neurogenic inflammation in the dura mater and tongue as evidenced by marked increases in mast cell activation, protein extravasation, as well as in the numbers of endothelial cytoplasmic vesicles, endothelial microvilli and platelet aggregates within ipsilateral post-capillary venules. In this report, we examined the effects of pretreatment with serotonin1 receptor agonists, dihydroergotamine (50 micrograms/kg, i.v.) and sumatriptan (100 micrograms/kg, i.v.) on the light and electron microscopic changes which develop after trigeminal ganglion stimulation. Both dihydroergotamine and sumatriptan are useful in the acute treatment of vascular headaches and bind with high affinity to 5-HT1D receptors. Both drugs decreased significantly the number of dural vessels showing endothelial or platelet changes and the numbers of activated mast cells, but did not affect the neurogenic response in the tongue. The drugs also blocked the accumulation of horseradish peroxidase reaction product within the endothelium and perivascular space on the stimulated side. The receptor is not present on trigeminovascular fibers innervating extracranial cephalic tissues. Drug mechanism probably involves inhibition of a proximal step in the pathophysiological cascade (e.g., via activation of a prejunctional receptor) because (a) receptors for sumatriptan have not been identified on mast cells whereas the inflammatory response was attenuated in mast cells as well as within platelets and the endothelium and (b) previous work indicates that sumatriptan and dihydroergotamine block neurotransmitter release. Hence, constriction of vascular smooth muscle mediated by postjunctional 5-hydroxytryptamine receptors is unlikely to explain the anti-inflammatory actions of dihydroergotamine or sumatriptan reported here.

The development of neurogenic plasma extravasation in the rat dura mater does not depend upon the degranulation of mast cells.

Mast cells were visualized in stretch preparations of the rat dura mater and were found mostly in relation to small and large blood vessels. The overall number of dural mast cells was unaffected by electrical trigeminal or chemical deafferentation. As in other tissues, mast cell degranulation increased at sites of local injury (electrode penetration) or after systemic treatment with compound 48/80. However, mast cells did not degranulate following electrical trigeminal stimulation, or after injection of drugs (capsaicin or substance P) which promote plasma extravasation in the dura. Furthermore, pretreatment with a mast cell stabilizer (sodium dicromoglycate) or with large doses of H1 and H2 histamine receptor blockers (mepyramine and cimetidine), did not block electrically- or chemically-induced neurogenic plasma extravasation (NPE). Daily pretreatment with 48/80 however completely attenuated or abolished NPE. Taken together these data suggest that as assessed by the extrusion of metachromatic granules, mast cells are not essential to the development of neurogenic inflammation within the rat dura mater. However, these findings cannot exclude the possibility that mast cells may amplify or modulate this process.

Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions.

The results of recent investigations designed to elucidate the neuroeffector functions of sensory fibres, the cause of migraine headache and the mechanism of action of antimigraine drugs are reviewed and discussed. Neurogenic inflammation (vasodilatation and neurogenic plasma extravasation) is one explanation for the development of headaches and the blood flow changes which occur during migraine headache. Numerous studies have recently been carried out on rats and guinea-pigs into the effects of antimigraine agents, including ergot alkaloids, sumatriptan and non-steroidal anti-inflammatory drugs (NSAIDs), on neurogenic plasma protein extravasation in the dura mater induced by electrical stimulation of trigeminal ganglia or systemic administration of capsaicin. It is known that the dura mater is able to produce headaches in man. Ergot alkaloids have been shown to block neurogenic inflammation via a C-fibre dependent neuronal mechanism. Sumatriptan appears to act fairly similarly although, whereas the ergot alkaloids are non-selective for either 5-hydroxytryptamine (5-HT; serotonin) receptors or 5-HT1, sumatriptan is selective for 5-HT1 receptors. The antimigraine action of NSAIDs may be via either an effect on blood vessels or an effect on the nerve fibre. The antimigraine effects of ergot alkaloids, sumatriptan and NSAIDs are discussed in the light of the common vasoconstrictor actions of these agents and knowledge that vasodilatation is apparently not responsible for migraine headache pain in most cases.

Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater.

Leakage of 125I-bovine serum albumin was measured in rat dura mater, conjunctiva, eyelid and lip, after unilateral electrical stimulation of the trigeminal ganglion. In one animal, 99Tc-human serum albumin leakage was imaged in ipsilateral facial tissues. Pretreatment with indomethacin 1 mg/kg i.p. decreased leakage in dura mater but not in extracranial tissues. When extravasation was expressed as a ratio of stimulated to unstimulated sides, indomethacin 1 mg/kg, or acetylsalicylic acid 50 mg/kg decreased this ratio from 1.80 to 1.27 (P less than 0.01) or from 1.84 to 1.21 (P less than 0.01), respectively. Dexamethasone (1 mg/kg i.p. tid X 1 day) caused only a very small decrease. Only large doses of indomethacin (10 mg/kg) or acetylsalicylic acid (50 mg/kg) reduced substance P (SP)-induced leakage in the dura. The latter results suggest that both drugs block plasma extravasation by acting on neuropeptides-induced changes in vascular permeability and/or smooth muscle contractility. However, inhibition of SP release from sensory axons cannot be excluded at concentrations which block neurogenic plasma extravasation but not SP-induced plasma leakage. Together, these results provide a possible mechanism for the therapeutic effects of indomethacin and acetylsalicylic acid in headache.

Increased density of dopamine D5 receptor in peripheral blood lymphocytes of migraineurs: a marker for migraine?

The expression of dopamine D5 receptor was investigated in peripheral blood lymphocytes of 11 migraine patients and of ten healthy control subjects using a radioligand binding technique with [3H]SCH 23390 as a ligand. [3H]SCH 23390 is a benzazepine derivative with potent antagonist properties at the dopamine D1-like receptors. [3H]SCH 23390 was specifically bound to peripheral blood lymphocytes of migraineurs and control subjects in a manner consistent with the labelling of a dopamine D5 receptor. In migraineurs a statistically significant higher density of lymphocyte dopamine D5 receptor compared with controls was noticeable, whereas the affinity of the radioligand was unchanged. The increased density of dopamine D5 receptor in peripheral blood lymphocytes may reflect the dopaminergic hypersensitivity displayed by migraineurs and may represent a relatively simple and reliable peripheral marker of altered dopaminergic function.