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BACKGROUND: the aim of this study was to investigate the neurophysiological effect of anti-CGRP monoclonal antibodies on central and peripheral levels in migraine patients. METHODS: An observational cohort study in patients with migraine was performed. All subjects underwent Single-Pulse and Paired-Pulse Transcranial Magnetic Stimulation, as well as a Pressure Pain Threshold assessment. The same protocol was repeated three and four months after the first injection of anti-CGRP monoclonal antibodies. RESULTS: A total of 11 patients with a diagnosis of migraine and 11 healthy controls were enrolled. The main findings of this study are the significant effects of anti-CGRP mAb treatment on the TMS parameters of intracortical inhibition and the rise in the resting motor threshold in our group of patients affected by resistant migraine. The clinical effect of therapy on migraine is associated with the increase in short-interval intracortical inhibition (SICI), resting motor threshold (RMT), and Pressure Pain Threshold (PPT). In all patients, all clinical headache parameters improved significantly 3 months after the first injection of mAbs and the improvement was maintained at the 1-month follow-up. At baseline, migraineurs and HCs had significant differences in all TMS parameters and in PPT, while at follow-up assessment, no differences were observed on RMT, SICI, and PPT between the two groups. After anti-CGRP monoclonal antibody injection, a significant increase in the intracortical inhibition, in the motor threshold, and in the Pressure Pain Threshold in critical head areas was observed in patients with migraine, which was related to significant clinical benefits. CONCLUSIONS: Anti-CGRP monoclonal antibodies improved clinical and neurophysiological outcomes, reflecting a normalization of cortical excitability and peripheral and central sensitization. By directly acting on the thalamus or hypothalamus and indirectly on the trigeminocervical complex, treatment with anti-CGRP monoclonal antibodies may modulate central sensorimotor excitability and peripheral sensitization pain.

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The most superficial layer of the spinal dorsal horn, lamina I, is a key element of the nociceptive processing system. It contains different types of projection neurons (PNs) and local-circuit neurons (LCNs) whose functional roles in the signal processing are poorly understood. This article reviews recent progress in elucidating novel anatomical features and physiological properties of lamina I PNs and LCNs revealed by whole-cell recordings in ex vivo spinal cord. This article is part of the Special Issue on "Ukrainian Neuroscience".

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Ocular neuropathic pain (ONP) has various etiologies, and patients have various symptoms. The clinical management of patients with ONP has been debated. We aimed to evaluate the effect of repeated greater occipital nerve block (GONB) on ONP based on convergence in the trigeminocervical complex. In this single-center retrospective study, the medical records of 204 patients who were referred to the pain clinic by the ophthalmology department of our hospital and subsequently underwent repeated GONB for chronic ONP between January 2008 and February 2022 were analyzed. They received GONB every two weeks, up to 10 times. Symptoms of ONP were divided into five categories: eye pain, dysesthesias/allodynia, non-eye pain, visual disturbance, and tearing. The primary outcome of this study was the pain relief scale (PRS) score after repeated injections. The differences and magnitude of decrease in the overall pain relief scale score were statistically significant (estimate = -0.55, p < 0.001). There were two patients who had recurrence of ONP and seven patients who had adverse events. According to our study, repeated GONB can reduce symptom severity in patients with ONP. Therefore, it appears that GONB can be considered a multimodal management method for ONP.

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BACKGROUND: Migraine is commonly seen as a cyclic disorder with variable cortical excitability at different phases. Herein, we investigated the cortical excitability in migraine without aura patients during an attack (MWoA-DA) and interictal period (MWoA-DI) and further explored the functional connectivity (FC) in brain regions with cortical excitability abnormalities in patients. METHODS: Seven MWoA-DA patients, twenty-seven MWoA-DI patients, and twenty-nine healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuations (ALFF) was assessed to identify spontaneous brain activity. Then, brain regions showing significant differences across groups were identified as regions of interest (ROI) in FC analysis. RESULTS: Compared with MWoA-DI patients and HC, the ALFF in the trigeminocervical complex (TCC) was higher in the MWoA-DA patients. Decreased FC in MWoA-DA patients was found between TCC and left postcentral gyrus compared with MWoA-DI patients. Compared with HC, ALFF was lower in the right cuneus but higher in the right rolandic operculum of MWoA-DI patients. Additionally, the ALFF in the right cuneus was negatively correlated with the Migraine Disability Assessment Scale (MIDAS) in MWoA-DI patients. CONCLUSIONS: The trigeminovascular system and impairments in descending pain modulatory pathways participate in the pathophysiology of migraine during the ictal period. The defense effect exists in the interictal phase, and the dysfunction in the cuneus may be related to the disease severity. This dynamic change in different brain regions could deepen our understanding of the physiopathology underlying migraine.

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Cervical and trigeminal afferents innervate neighboring cranial territories, and their convergence on upper cervical dorsal horn neurons provides a potential substrate for pain referral in primary headache syndromes. Lamina I neurons are central to this mechanism, as they relay convergent nociceptive input to supraspinal pain centers. Unfortunately, little is known about the interactions between trigeminal and cervical afferents supplying Lamina I neurons. Here, we used rats of both sexes to show that cervical and trigeminal afferents interact via presynaptic inhibition, where monosynaptic inputs to Lamina I neurons undergo unidirectional as well as reciprocal presynaptic control. This means that afferent-driven presynaptic inhibition shapes the way trigeminal and cervical Aδ-fiber and C-fiber input reaches Lamina I projection neurons (PNs) and local-circuit neurons (LCNs). We propose that this inhibition provides a feedforward control of excitatory drive to Lamina I neurons that regulates their convergent and cervical-specific or trigeminal-specific processing modes. As a consequence, disruption of the trigeminal and cervical afferent-driven presynaptic inhibition may contribute to development of primary headache syndromes.SIGNIFICANCE STATEMENT Cervical and trigeminal afferents innervate neighboring cranial territories, and their convergence on upper cervical dorsal horn neurons provides a potential substrate for pain referral in primary headache syndromes. Lamina I neurons are central to this mechanism as they relay convergent nociceptive input to supraspinal pain centers. Here, we show that cervical and trigeminal afferents interact via presynaptic inhibition, where inputs to Lamina I neurons undergo unidirectional as well as reciprocal control. The afferent-driven presynaptic inhibition shapes the trigeminocervical Aδ-fiber and C-fiber input to Lamina I neurons. This inhibition provides control of excitatory drive to Lamina I neurons that regulates their convergent and cervical-specific or trigeminal-specific processing modes. Disruption of this control may contribute to development of primary headache syndromes.

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OBJECTIVE: Persistent headache attributed to whiplash (PHAW) is defined as a headache that occurs for the first time in close temporal relation to whiplash lasting more than 3 months. We investigated the results of decompression of the greater occipital nerve (GON) in patients with PHAW who presented with referred trigeminal facial pain caused by sensitization of the trigeminocervical complex) along with occipital headache. METHODS: A 1-year follow-up study of GON decompression was conducted in 7 patients with PHAW manifesting referred facial trigeminal pain. The degree of pain reduction was analyzed using the numeric rating scale (NRS-11) and percent pain relief before and 1 year after surgery. Success was defined by at least 50% reduction in pain measured via NRS-11. To assess the degree of subjective satisfaction, a 10-point Likert scale was used. Clinical characteristics of headache and facial pain and surgical findings were studied. RESULTS: GON decompression was effective in all 7 patients with PHAW manifesting referred trigeminal pain, with a percent pain relief of 83.06 ± 17.30. The pain had disappeared in 3 of 7 patients (42.9%) within 6 months and no further treatment was needed. Patients' assessment of subjective improvement based on a 10-point Likert scale was 7.23 ± 1.25. It was effective in both occipital and facial pain. CONCLUSIONS: Although chronic GON entrapment itself is an individual constitutional issue, postwhiplash inflammatory changes seem to trigger chronic occipital headaches in GON distribution and unexplained referred trigeminal pain caused by sensitization of the trigeminocervical complex.

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Craniofacial neuropathic pain affects millions of people worldwide and is often difficult to treat. Two key mechanisms underlying this condition are a loss of the negative control exerted by inhibitory interneurons and an early microglial reaction. Basic features of these mechanisms, however, are still poorly understood. Using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic pain in mice, we have examined the changes in the expression of GAD, the synthetic enzyme of GABA, and GlyT2, the membrane transporter of glycine, as well as the microgliosis that occur at early (5 days) and late (21 days) stages post-CCI in the medullary and upper spinal dorsal horn. Our results show that CCI-IoN induces a down-regulation of GAD at both postinjury survival times, uniformly across the superficial laminae. The expression of GlyT2 showed a more discrete and heterogeneous reduction due to the basal presence in lamina III of 'patches' of higher expression, interspersed within a less immunoreactive 'matrix', which showed a more substantial reduction in the expression of GlyT2. These patches coincided with foci lacking any perceptible microglial reaction, which stood out against a more diffuse area of strong microgliosis. These findings may provide clues to better understand the neural mechanisms underlying allodynia in neuropathic pain syndromes.

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BACKGROUND AND OBJECTIVE: The importance of neck pain and the trigeminocervical complex in migraine is of high pathophysiological interest since a block to the greater occipital nerve is more effective for some primary headaches than others. This observational study hypothesised that the response to manual palpation of the upper cervical spine predicts the efficacy of the greater occipital nerve-block. METHODS: We divided patients, scheduled by a neurologist to receive a greater occipital nerve-block to reduce their migraine symptoms, into three groups: Patients with no pain response to manual palpation of the neck, patients with local pain, and those with referred pain to the head. Primary outcome was the percentage change in headache frequency. Additionally, items from the quantitative sensory testing protocol were included. RESULTS: Eighty-seven chronic migraine patients were recruited consecutively from a specialised outpatient clinic and 71 were included for analyses and stratified into the three groups: No pain (n = 11), local pain (n = 28), and referred pain to the head (n = 32). Overall, patients experienced a reduction of 1.9 headache days per month (SD 3.4, p < 0,0001). The groups differed significantly in the percentage change of headache frequency (p = 0.041) with the "no pain" group showing the largest reduction. The pressure-pain-threshold over C2 and headache on the day of the intervention influenced the outcome significantly (R2 0,27, p = 0,00078). No serious adverse events occurred. Sixty-five percent of the patients had headaches during the examination. The groups did not differ regarding the distribution of patients with neck-pain in absence of migraine at baseline (p = 0.618). CONCLUSION: Patients that were less sensitive to palpation in the cervical region and headache-free on the day of the intervention improved more after the greater occipital nerve-block.Registration: Registered a priori at the German Clinical Trials Register (DRKS00015995).

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PURPOSE: This rat experiment aims to demonstrate the efficacy of electrical acupuncture in preventing migraine attacks by stimulating the acupoint GB20. INTRODUCTION: Migraine, which takes 2ed at level four causes of GBD's disease hierarchy, becomes a public health issue. It is important for physicians to supplement their knowledge of its treatment and consider alternative methods of therapy, such as acupuncture. However, the neurobiological and pathophysiological mechanisms of this prophylactic effect were unclear. The trigeminocervical complex is thought to be an important relay station in migraine pathophysiology as the key nuclei of the trigeminovascular system and the brainstem descending pain modulation system. METHODS: There were six groups involved in this study: control, model, electroacupuncture, non-acupoint electroacupuncture, saline+electroacupuncture and saline+non-acupoint electroacupuncture. We injected saline or inflammatory soup into dura mater to induce control or migraine in the rats. The mechanical pain threshold and the single-cell extraneural neurophysiology of the C1 spinal dorsal horn neurons in the trigeminocervical complex were detected. RESULTS: Pre-electroacupuncture could significantly increase the mechanical pain threshold of the periorbital region receptive field of the trigeminal nerve and decrease the discharges of neurons in the trigeminocervical complex. Acupuncture also reversed the abnormal skin pain response of the periorbital region receptive field of the trigeminal nerve caused by low-intensity stimulation. DISCUSSION: We believe that our study makes a significant contribution to the literature because it is the first of its kind to use GB20 to provide relief from migraine attacks and mechanical cephalic cutaneous hypersensitivity by regulating the neuronal discharge from trigeminocervical complex.

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INTRODUCTION: Acupuncture has become a relevant complementary and alternative treatment for acute migraine; however, the neurophysiological mechanism (C-fibers) underlying this effect remains unclear. C-fibers play a crucial role for diffuse noxious inhibitory controls (DNIC) at wide dynamic range (WDR) neurons in the trigeminocervical complex (TCC) in migraine attacks, and we supposed that this may be the mechanism of acupuncture analgesia. This study aimed to examine the neurophysiology of acupuncture intervention in an acute migraine rat model. METHODS: Inflammatory soup (IS) or saline was injected into the dura mater to establish a migraine and control model in rats. To explore the neurobiological mechanism of acupuncture for migraine, we implemented electro-acupuncture (EA), non-electric-stimulation acupuncture, and no-acupuncture in IS and saline injected rats, and recorded the single-cell extraneural neurophysiology of the atlas (C1) spinal dorsal horn neurons in the TCC. RESULTS: Our research shows that electro-acupuncture at GB8 (Shuaigu), located in the periorbital region receptive field of the trigeminal nerve, may rapidly reduce the C-fiber evoked WDR neuronal discharges of the TCC within 60 s. DISCUSSION: This study provides pioneering evidence of a potential neurobiological mechanism for the analgesic effect on migraine attacks achieved by electro-acupuncture intervention via DNIC. The data indicates that EA may become a crucial supplementary and alternative therapy for migraineurs that failed to respond to acute medications, e.g., fremanezumab, which achieves its analgesic effect via modulating Aσ-fibers, not C-fibers.

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BACKGROUND AND OBJECTIVE: Successful preventive treatment in chronic migraine (CM) remains an unmet need in some cases, and new therapeutic strategies are emerging. We aimed to test the effect of noninvasive, transcutaneous supraorbital nerve stimulation (tSNS) in a group of patients with CM. PATIENTS AND METHODS: This was an open label, quasi-experimental design. Twenty-five CM patients were recruited from two hospital headache clinics. After a one-month baseline period, monthly visits were scheduled during three months. Headache occurrence, its intensity, and symptomatic medication intake were recorded through a diary kept by each patient. Both a per-protocol analysis and an intention-to-treat analysis were performed for the main outcome measures. RESULTS: Twenty-one and 24 patients were included in the per-protocol and the intention-to-treat analyses, respectively. In the per-protocol analysis, a significant four-day decrease in the mean monthly days with moderate or severe headache was observed from baseline to the end of the study (t test, P = 0.0163), and there was a nonsignificant reduction of 2.95 in the mean monthly total headache days. In the intention-to-treat analysis, a nonsignificant 3.37 reduction in the mean monthly days with moderate or severe headache was observed for the same period, and there was a significant 2.75 reduction in the mean monthly days with any headache (t test, P = 0.016). CONCLUSIONS: tSNS could hold preventive properties in the treatment of CM, but the effect may be either mild or controversial. Double blind, sham-controlled studies are essential to confirm these findings and to outline their clinical relevance in the CM therapeutic scenario.

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A unique case is presented of chronic occipital neuralgia (ON) caused by cavernous malformation (CM) in the intramedullary C2 spinal cord and subsequent pain relief and remodeling of allodynic pain following dorsal root rhizotomy. A 53-year-old male presented with a 30-year history of chronic allodynic, paroxysmal lancinating pain in the greater and lesser occipital nerves. Typically, the pain was aggravated with neck extension and head movement. Magnetic resonance imaging showed a CM in the right posterolateral side of the intramedullary C2 cord. Considering potential risks associated with removal of the lesion, intradural C1-3 dorsal root rhizotomy with dentate ligament resection was performed. The paroxysmal lancinating pain of ON was significantly alleviated, and the remodeling of the extent of allodynic pain was noted after C1-3 dorsal root rhizotomy. These changes gradually occurred during the second postoperative month, and this effect was maintained for 24 months postoperatively. Significant reduction in chronic allodynic pain of secondary ON caused by cervicomedullary CM involving central sensitization in the trigeminocervical complex was observed with reduction of irritating, afferent input with C1-C3 dorsal root rhizotomy.

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Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.

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The somatotopy of the trigeminocervical complex of the rat was defined as a basis for describing circuitry for reflex behaviors directed through the facial motor nucleus. Thus, transganglionic transport of horseradish peroxidase conjugates applied to individual nerves/peripheral receptive fields showed that nerves innervating oropharyngeal structures projected most rostrally, followed by nerves innervating snout, periocular, and then periauricular receptive fields most caudally. Nerves innervating mucosae or glabrous receptive fields terminated densely in laminae I, II, and V of the trigeminocervical complex, while those innervating hairy skin terminated in laminae I-V. Projections to lamina II exhibited the most focused somatotopy when individual cases were compared. Retrograde transport of FluoroGold (FG) deposited into the facial motor nucleus resulted in labeled neurons almost solely in lamina V of the trigeminocervical complex. The distribution of these labeled neurons paralleled the somatotopy of primary afferent fibers, e.g., those labeled after FG injections into a functional group of motoneurons innervating lip musculature were found most rostrally while those labeled after injections into motoneurons innervating snout, periocular and preauricular muscles, respectively, were found at progressively more caudal levels. Anterograde transport of injections of biotinylated dextran amine into lamina V at different rostrocaudal levels of the trigeminocervical complex confirmed the notion that the somatotopy of orofacial sensory fields parallels the musculotopy of facial motor neurons. These data suggest that neurons in lamina V are important interneurons in a simple orofacial reflex circuit consisting of a sensory neuron, interneuron and motor neuron. Moreover, the somatotopy of primary afferent fibers from the head and neck confirms the "onion skin hypothesis" and suggests rostral cervical dermatomes blend seamlessly with "cranial dermatomes." The transition area between subnucleus interpolaris and subnucleus caudalis is addressed while the paratrigeminal nucleus is discussed as an interface between the somatic and visceral nervous systems.

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Migraine as primary headache is a life-long disease which is relevant for the quality of life and is based on complex genetics. It often starts in childhood with symptoms typical for the specific age. These show different nuances compared to the migraine symptoms in adults, for example, regarding (bilateral/unilateral) localization of the acute migraine headache. Only over the course of years-during adolescence and young adulthood-do the more specific symptoms as defined by the International Classification of Headache Disorders (ICHD 3 beta) develop. In this article we focus on the clinical specifics of children and adolescents with migraine. We elaborately refer to the trigeminocervical complex (TCC) because it forms a conceptual bridge for the understanding of migraine, for psychoeducation, and for therapeutic options. We pragmatically discuss options and limits of treatments.

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Migraine is a common neurological disease with a high prevalence and unsatisfactory treatment options. The specific pathophysiological mechanisms of migraine remain unclear, which restricts the development of effective treatments for this prevalent disorder. The aims of this study were to 1) compare the spontaneous brain activity differences between Migraine without Aura (MwoA) patients and healthy controls (HCs), using amplitude of low-frequency fluctuations (ALFF) calculation method, and 2) explore how an effective treatment (verum acupuncture) could modulate the ALFF of MwoA patients. One hundred MwoA patients and forty-six matched HCs were recruited. Patients were randomized to four weeks' verum acupuncture, sham acupuncture, and waiting list groups. Patients had resting state BOLD-fMRI scan before and after treatment, while HCs only had resting state BOLD-fMRI scan at baseline. Headache intensity, headache frequency, self-rating anxiety and self-rating depression were used for clinical efficacy evaluation. Compared with HCs, MwoA patients showed increased ALFF in posterior insula and putamen/caudate, and reduced ALFF in rostral ventromedial medulla (RVM)/trigeminocervical complex (TCC). After longitudinal verum acupuncture treatment, the decreased ALFF of the RVM/TCC was normalized in migraine patients. Verum acupuncture and sham acupuncture have different modulation effects on ALFF of RVM/TCC in migraine patients. Our results suggest that impairment of the homeostasis of the trigeminovascular nociceptive pathway is involved in the neural pathophysiology of migraines. Effective treatments, such as verum acupuncture, could help to restore this imbalance.

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Background Although the peripheral and central sensitizations of trigeminal nervous system may be one of the important factors of migraine, the precise mechanism is not fully understood. In this study, we examined the influence of the sensitization of the second division of the trigeminal nerve (V2) by chronic constriction injury (CCI) of the infraorbital nerve (ION) on migraine headache, using the capsaicin-induced migraine model. Methods Male Sprague-Dawley rats were assigned to four groups: (a) sham surgery and topical-dural vehicle application (Sham + Vehicle) group, (b) CCI-ION and topical-dural vehicle application (CCI-ION + Vehicle) group, (c) sham surgery and topical-dural capsaicin application (Sham + Capsaicin) group, (d) CCI-ION and topical-dural capsaicin application (CCI-ION + Capsaicin) group. Behavioral testing and immunohistochemical staining were performed. Results In the behavioral test, the Sham + Capsaicin group showed significantly longer duration of immobilization and shorter duration of exploration compared with the Sham + Vehicle group, which is similar to clinical features of migraine patients. Moreover, CCI-ION enhanced these effects in the CCI-ION + Capsaicin group. Immunohistochemical staining for phospho-extracellular signal-related kinase (pERK) in the trigeminal ganglion (TG) containing first and second divisions of the trigeminal nerve and the trigeminocervical complex (TCC) revealed that pERK expression was significantly increased in the CCI-ION + Capsaicin group compared with the other groups. However, comparing between effects of the peripheral and central sensitizations (in the TG and TCC), from our results, peripheral sensitization would play a much less or not significant role. Conclusions These data demonstrate that the sensitization of V2 could influence the activation and the sensitization of the first division of the trigeminal nerve in the TCC, subsequently exacerbating pain sensation and pain-related behaviors. We have shown for the first time that the existence of the central sensitization of V2 can be an exacerbating factor for migraine related nociceptive thresholds/activation.

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OBJECTIVE: Trigeminal and cervical afferents converge on neurons of the trigeminocervical complex and may significantly alter the function of these neurons. This interaction may have implications for the pathophysiology and treatment of primary headache disorders. Therefore, the aim of this work was to study pain modulatory mechanisms within the trigeminocervical complex. SUBJECTS: We used an electrical pain model challenging pro- and antinociceptive systems in 19 healthy volunteers. METHODS: Transcutaneous supraorbital noxious electrical low-frequency stimulation (0.5 Hz), known to induce both hyperalgesia due to central sensitization (as a marker of pain facilitation) and habituation (as a marker of pain inhibition), was combined with different noxious stimulation paradigms applied to the innervation territory of upper cervical afferents. We investigated the effects of concurrent stimulation in the cervical/extratrigeminal system on habituation profiles, hyperalgesic area, pain, and detection thresholds in the trigeminal system. RESULTS: It was previously shown that conditioning 20-Hz noxious electrical stimuli may provoke centrally mediated sensory decline that possesses heterotopic antihyperalgesic properties. Occipital and forearm costimulation at a frequency of 20 Hz had no significant modulating effect on supraorbital pain adaptation, hyperalgesic area, or pain perception. Effects for trigeminal stimulation were independent of occipital stimulus intensity. Furthermore, for single occipital stimulation at 0.5 and 20 Hz, no somatosensory changes could be demonstrated within the trigeminal system. CONCLUSION: Trigeminal nociception stayed unchanged despite of occipital costimulation.

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Objective To detect the expressions of peroxisome proliferator-activated receptor (PPAR) isotypes (PPARα,PPARβ/δ and PPARγ) in migraine rat models induced by nitroglycerin and their roles in morbidity mechanism.Methods Forty-eight SD rats were randomly divided into normal control group,physiological saline control group and migraine model group (n=16).The rat migraine models were established according to Tassorelli Cristina method and performed abdominal subcutaneous injection of nitroglycerin at a dosage of 9.5 mg/kg; rats in the physiological saline control group were given the same volume of physiological saline and that in the normal control group did not receive any treatment.The trigeminocervical complexes were separated from rats in each group.Expressions of PPARα,PPARβ/δ and PPARγ were detected by Western blotting and immunohistochemical method.Results Immunohistochemical staining showed strong positive expressions of PPARα,PPARβ/δ and PPARγ in model group,which were higher than those in normal control group and physiological saline control group.Western blotting indicated that the expressions of PPARα,PPARβ/δ and PPARγγof the trigeminocervical complexes in model group were 0.361 ±0.051,0.372 ±0.061 and 0.654 ±0.101,respectively,which were also significantly higher than those in normal control group and physiological saline control group (P＜0.05).Conclusions The expressions of PPARα,PPARβ/δ and PPARγγin the trigeminocervical complexes in migraine rats are increased,which might be a compensatory neuroprotective response in the occurrence of migraine.